Tag Archives: E. Coli

Silver nanoparticles change shape and get ‘consumed’ when destroying bacteria

New research is looking into the interaction between silver nanoparticles and E. coli bacteria as a possible solution to the growing levels of antibiotic resistance seen in pathogens. Although the antibacterial effect of silver has been known for some time now, we didn’t understand why it had this effect.

Silver bars. Image via Pixabay.

Silver has seen growing use for pathogen control in the last few years, in things such as antimicrobial coatings, for example. So far, it definitely seems to be good at the job of killing these tiny threats. Still, a better understanding of how and why it can protect from microbes could help us better apply silver to the task.

In order to glean this information, a team of researchers monitored the interactions between silver nanoparticles and a culture of E. coli bacteria. According to the results, silver nanoparticles undergo several dramatic changes in properties such as size and shape while interacting with bacteria.

Silver for monsters

Concerning the issue of antibiotic resistance, silver poses a very exciting prospect in that it physically kills bacteria, not chemically, as our drugs do. In other words, pathogens don’t have any way of defending themselves against silver.

An international team of researchers with members from Italy, the United States, and Singapore report that silver nanoparticles go through “several dramatic” changes when interacting with E. coli bacteria. This goes against the current prevailing wisdom that the metal remains unaltered during such interactions.

These changes seem to originate in electrostatic interactions between the silver and the bacteria. This causes some of the nanoparticles to dissolve and spread as ions in the environment, eventually making their way into the bacterial cells. Their shape changes as they dissolve, getting smaller and more rounded (they start out as triangular shapes).

After observing these mechanisms, the team treated their E. coli colony with a substance that increased the permeability of the bacteria’s membranes, and then tested them again. In this case, the effects on the silver were more pronounced, they explain.

“It seems from this study that silver is ‘consumed’ from the interaction,” said Guglielmo Lanzani, one of the authors on the paper and director of the Center for Nano Science and Technology of IIT-Istituto di Tecnologia.

“We think this does not affect the efficiency of the biocidal process and, due to the tiny exchange of mass, the lifetime is essentially unlimited,” said Giuseppe Paternò, a researcher at IIT and co-author of the study. “The structural modifications, however, affect the optical properties of the metal nanostructures.”

Although the findings help us better understand the interactions between bacteria and silver nanoparticles, they’re likely not the entire story, the authors note. Laboratories are highly controlled environments, and as such cannot begin to capture everything that’s going on in the wild. These factors that are left out might have an important hand to play in shaping the final interaction between bacteria and silver.

Even so, the team will continue to explore this topic, with a particular interest in studying the chemical machinery (‘chemical pathways’) inside the bacteria that cause these structural changes in silver. They also want to understand why silver is a more powerful antibacterial agent than other materials, and why bacterial membranes seem to be so vulnerable to it while our cells are almost unaffected.

The paper “The impact of bacteria exposure on the plasmonic response of silver nanostructured surfaces” has been published in the journal Chemical Physics Reviews.

New approach neutralizes influenza with modified bacteria predator membranes

A team of German researchers has developed a new way to deal with seasonal and avian influenza viruses. Their approach involves wrapping the pathogens in chemically-modified bacteriophage capsids, rendering them unable to infect human cells.

Electron micrograph of coliphages (a type of bacteriophage) attached to a bacterial cell. Image credits: Dr Graham Beards via Wikimedia.

The team hopes their work will help usher in new treatment options against such viruses. The method was tested in the lab with very encouraging results and is currently under investigation for possible applications against the coronavirus.

Viral straightjacket

“Pre-clinical trials show that we are able to render harmless both seasonal influenza viruses and avian flu viruses with our chemically modified phage shell,” explained Professor Dr. Christian Hackenberger, Head of the Department Chemical Biology at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) and Leibniz Humboldt Professor for Chemical Biology at HU Berlin. “It is a major success that offers entirely new perspectives for the development of innovative antiviral drugs.”

Current antiviral treatments only attack the influenza virus after it has infected our cells, the team reports, which is certainly useful — but preventing infection in the first place would be much more desirable and effective.

The trials — which used infected human lung tissue samples — showed that perfectly fitting a phage capsid onto these viruses can be used to neutralize their ability to infect lung cells. The capsid was specially developed by the team for this job, and works by binding itself to all the (hemagglutinin) proteins the virus can use to gain access through the membranes of human cells. During the infection process, these proteins bind to sugar molecules sprinkled through the membrane of lung tissue cells to allow entry. The core mechanism of this process, however, relies on the virus creating multiple bonds with a cell, rather than a single one.

Their quest to develop an inhibitor for these proteins started six years ago. The plan was to make such an inhibitor functionally resemble the membrane of a human lung cell. The team’s quest led them to the Q-beta phage, a harmless species of bacteriophage that lives in our intestines and usually preys on E.coli. The team removed and attached ligands (binders) to its casing — sugar molecules in this case — to act as bait binding sites for the virus’ proteins

“Our multivalent scaffold molecule is not infectious, and comprises 180 identical proteins that are spaced out exactly as the trivalent receptors of the hemagglutinin on the surface of the virus,” explained Dr. Daniel Lauster, a former Ph.D. student in the Group of Molecular Biophysics (HU) and now a postdoc at Freie Universität Berlin. “It therefore has the ideal starting conditions to deceive the influenza virus — or, to be more precise, to attach to it with a perfect spatial fit. In other words, we use a phage virus to disable the influenza virus!”

When samples of tissue infected with flu viruses were treated with the phage capsid, the influenza viruses were practically unable to reproduce. High-resolution cryo-electron microscopy and standard cryo-electron microscopy revealed that the modified capsids completely cover the viruses.

While definitely encouraging, the findings call for more preclinical studies to assess the method’s viability and safety for human use. We don’t yet know, for example, if the capsids themselves would elicit an immune response in mammals, and if such a response would enhance or impair their effect. And, of course, it has yet to be proven that the inhibitor is also effective in humans.

For now, the team is content to know that their approach has great potential and that it is “the first achievement of its kind in multivalency research,” according to Professor Hackenberger. The approach, he adds, is biodegradable, non-toxic, doesn’t cause an immune response in cell cultures, and is, at least in principle, applicable to other viruses and possibly even bacteria. The team is currently focusing on adapting it to the SARS-CoV-2 virus.

The paper “Phage capsid nanoparticles with defined ligand arrangement block influenza virus entry” has been published in the journal Nature Nanotechnology.

E. coli superbugs linked to poor hygiene and not contaminated food

Despite it has usually been associated with undercooked chicken or other food, antibiotic-resistant E. coli is actually more likely to be spread through poor toilet hygiene, according to new research.

Credit Wikipedia Commons

Millions of bacteria naturally populate the guts of humans and animals alike, with different species coexisting in a fine balance that ensures a state of health. Some strands of E. coli form part of the natural gut microbiome and are usually harmless.

However, sometimes, a person may come into contact with strains of this bacterium that have developed antibiotic resistance. When this happens, E. coli may cause food poisoning, urinary tract infections, or intestinal infections.

Two possible sources of E. coli infections are contaminated food items and poor personal hygiene. But it remains unclear which one of these sources is most likely to lead to infection, and that is what researchers set out to learn.

In their study, published in The Lancet, the researchers collected antibiotic-resistant E. coli strains from meat (chicken, pork, and beef), animal slurry, salad, and fruit, on the one hand, and human bloodstream infections, feces, and sewage, on the other. The samples came from the National Health Service (NHS) laboratories.

Typically, antibiotic-resistant strains of this bacterium feature extended-spectrum beta-lactamases (ESBLs), enzymes that neutralize the action of antibiotics that people use to fight E. coli, such as penicillin and cephalosporin. Scientists refer to such strains of E. coli as “ESBLs-E. coli.

The researchers’ analysis revealed that resistant E. coli strains present in the samples of human blood, feces, and sewage had lots of similarities. The dominant strain present in samples of human origin was ST131. In samples of food, however, the researchers found barely any traces of ST131. Instead, they noticed the presence of other ESBL-E. coli strains.

The almost complete lack of a crossover of E. coli strains between samples of human origin and those taken from contaminated foods suggested to the study authors that most infections with antibiotic-resistant E. coli are, most likely, transmitted from human to human as a result of poor hygiene practices.

“Critically — there’s a little crossover between strains from humans, chickens, and cattle. The great majority of strains of ESBL-E. coli causing human infections aren’t coming from eating chicken, or anything else in the food chain,” notes Prof. Livermore. “Rather — and unpalatably — the likeliest route of transmission for ESBL-E. coli is directly from human to human.”

Still, researchers noted that the findings do not mean people should stop being careful about how they handle foods, as food remains a source of infection.

“We need to carry on cooking chicken well and never to alternately handle raw meat and salad,” the lead author says. “There are plenty of important food-poisoning bacteria, including other strains of E. coli, that do go down the food chain.”

Researchers create bacteria synthetic DNA

Researchers have produced E. coli bacteria with completely synthetic DNA. While the research was aimed at studying genetic redundancies, the potential applications are limitless.

E. coli. Image credits: NIAID.

Researchers at the University of Cambridge have rewritten the DNA of the bacteria Escherichia coli, a strain of bacteria that is normally found in soil and the human gut. Although the bacteria look a bit weird and have some issues reproducing, they are alive and seem to function relatively normally — running by a set of rules directed by the human-edited genome.

For all its diversity and variation, all life on Earth (with the exception of some viruses) is based on DNA. The two-stranded DNA molecule is the blueprint for life as we know it, and each strand is composed of molecules containing just four bases: adenine, cytosine, guanine, and thymine (or A, C, G and T). Think of it this way: a handful of chemical letters are used to made three-letter words, and these words are then passed out as biological orders to proteins.

The four letters can be strung into 64 combinations of three-letter words called codons. Nearly all life on Earth uses these 64 codons, and these codons join to form virtually all proteins that can be found in nature — with the mention that three codons are used as punctuation marks, separating individual codons from one another.

However, there is a lot of redundancy within these combinations. Many combinations do the same thing, so they can theoretically be removed — but where do you stop? In order to study this, Jason Chin, an expert in synthetic biology who led the project, conducted a genetic “word swap”. He went through the bacteria’s DNA, and whenever he came across a particular codon (TCG, a codon that makes an amino acid called serine), he rewrote it as another one (AGC, which does the same job). He did this for three sets of codons, but the resulting genome was too long and complicated to brute-force in a cell — so instead, researchers split it into small segments and swapped them piece by piece inside the E. coli genome. By the time they were done, there were no natural segments in the bacteria’s DNA; the whole thing was synthetic.

The team then watched the bacteria go about its life. The first good news came immediately: it lived. It grew slower and presumably weaker than its “normal” version, but it was very much alive.

It’s not the first time a bacteria has been created with a synthetic DNA, but this achievement is by far the most complex achievement. In 2010, researchers from the J. Craig Venter Institute in Maryland created the first cell with synthetic DNA. In 2017, researchers at the Scripps Institute unveiled the first stable, semi-synthetic organism. Researchers are slowly starting to experiment with nature’s lifeforms and moving towards Life 2.0. Knowing which codons we need and which can be dropped is essential for this, especially as other groups are working on creating synthetic DNA for even more complex creatures such as baker’s yeast. The potential applications are limitless.

In addition to shedding new light on the chemical intricacies of DNA, this type of designer bacteria can also come in handy in the medical industry. They could, for instance, stop viral infections, or deliver diabetes or other compounds for treating serious conditions such as cancer and heart disease. After a certain point, you could even use it for more frivolous purposes, such as creating tastier bread or beer.

There is, however, a very strong impediment to this type of study: costs. Producing and inserting synthetic DNA is still an extremely expensive pursuit. Now that we know it can be done, we also know that in theory, you can recode anything. Actually having the know-how and the resources to do that remains a different matter.

The study has been published in Nature.

E.coli rendering.

Some bacteria can ‘hibernate’ through antibiotic treatments, new paper finds

When antibiotics come knocking, bacteria may simply sleep the threat away.

E.coli rendering.

Digital rendering of E.coli bacteria.
Image via Fotolia.

Researchers from the University of Copenhagen report that pathogenic bacteria have a surprising defensive tactic against antibiotics: hibernation. The research might help us fight antibiotic-resistant infections.

Nap it out

Almost all types of pathogenic bacteria eventually develop strains that are tolerant of or resistant to antibiotic treatments. This is particularly problematic as the fraction of bacteria which survive treatment — although tiny — can later multiply, maintaining infection in the face of our antibiotic efforts.

However, a small number of bacterial species do away with this mechanism completely, yet still retain the ability to resist the drugs meant to kill them. In an effort to understand why, the Copenhagen team turned to E. coli.

“We studied E. coli bacteria from urinary tract infections that had been treated with antibiotics and were supposedly under control,” says Professor Kenn Gerdes of the University of Copenhagen’s Department of Biology, paper co-author.

“In time, the bacteria re-awoke and began to spread once again,” he explains

The team found that a few individuals in the overall bacterial population ‘hid’ from the antibiotics in a dormant, hibernation-like state. The bugs slept through the treatment, and only resumed their regular activity once the dangerous compounds were removed.

Antibiotics generally work by attacking a bacteria cell’s ability to grow — so these hibernating individuals are virtually immune to their effects.

“A bacterium in hibernation is not resistant. It is temporarily tolerant because it stops growing, which allows it to survive the effects of an antibiotic,” says Professor Gerdes.

Hibernating bacteria seem to share the same genetic characteristics as all other individuals in a given population, the team reports. So, as of right now, they can’t say exactly why some members enter a dormant state while their peers do not. The team did, however, identify an enzyme in dormant individuals that governs the ‘hibernation’ process. A compound that could interfere with this enzyme’s functioning, or its synthesis, could help to keep these bacteria from becoming invulnerable to antibiotics.

“The discovery of this enzyme is a good foundation for the future development of a substance capable of combating dormant bacteria cells,” says Professor Gerdes.

“The enzyme triggers a ‘survival program’ that almost all disease-causing bacteria deploy to survive in the wild and resist antibiotics in the body. Developing an antibiotic that targets this general programme would be a major advance,” he adds.

Although the findings are encouraging, it will still be several years before they can be turned into a safe and useable treatment, the team writes.

The paper “The kinases HipA and HipA7 phosphorylate different substrate pools in Escherichia coli to promote multidrug tolerance” has been published in the journal Science Signaling.

British surfers are more prone to be antibiotic resistant bacteria carriers

A new study shows that surfers are three times more likely to harbor very resistant types of E.coli.

Surfers swallow almost ten times more seawater than the average swimmer, researchers at the University of Exeter report. Since many sewage collections drain into the sea, they sometimes bring along various types of Antibiotic-Resistant Bacteria (ARB). Researchers suspected that surfers ingest a worrying amount of such bacteria.

Source: Pixabay/andyperdana69

Dr Anne Leonard, lead author of the paper said: “This research is the first of its kind to identify an association between surfing and gut colonisation by antibiotic resistant bacteria.”

Unfit antibiotic treatments for viral infections and not respecting the full length and dosage of such treatments, are catalysts for bacterial resistance, a problem which is becoming more and more worrisome.

Bacteria are living organisms and the laws of evolution apply to them just like other creatures. When you take a treatment that kills most but not all bacteria, you’re accelerating their evolution. The survivors will be super trained to resist treatment. In a way, antibiotic resistance is their only way of surviving and adapting.

Via Pixabay/geralt

Surfing with the bugs

Scientists isolated many genes responsible for allowing Enterobacteriae (the family which includes E. coli) to survive antibiotics. One group, the blaCTX-M genes, confers resistance to multiple beta-lactam antibiotics.

Researchers analyzed 97 bathing water samples from England and Wales, noting the proportion of E. coli harboring blaCTX-M.They discovered that 11 out of the 97 bathing water samples were contaminated with the super-bug.

After they identified surfers as being at risk of exposure to ARB, scientists compared surfers and non-surfers to see whether there was an association between surfing and gut colonization by blaCTX-M- bearing E. coli.

The scientists discovered that 9 out of 143 (6.3%) surfers were colonized by blaCTX-M-bearing E. coli, as compared with 2 out of 130 (1.5%) of non-surfers.

Professor Colin Garner, founder and manager of Antibiotic Research UK — the only charity in the world set-up to tackle antibiotic resistance — said this was a “pioneering finding”.

He said that antibiotics enter the environment from farms or sewage. Environmental samples “have higher antibiotic concentrations than patients being administered antibiotics”.

“Research into new medicines to replace our archaic antibiotics has stagnated and unless new treatments are found, this could be potentially devastating for human health,” Professor Garners added.

“We know very little about the spread of antibiotic resistant bacteria and resistance genes between our environment, farm animals, wild animals and humans.”

Source: Pixabay/n4pgw

“This research helps us understand better the movement of resistant bacteria in surfers,” he said, but the next step should be testing if surfers and those in close contact with them are at greater risk of serious infection.

DNA.

DNA just got a major update, with readable synthetic nucleotides

Earlier this year, scientists were unveiling the first, stable semi-synthetic life form. In a paper published today, another research group reports enabling their spawn to read and use the synthetic genetic data, creating compounds entirely new to biological systems.

DNA.

Image credits Colin Behrens.

This year started off with a bang for everyone even remotely interested in the fields of genetics and genetic engineering when researchers from the Scripps Research Institute, California, announced the creation of a stable organism carrying semi-synthetic DNA. While it might not sound like much, the result was a breakthrough. Virtually all life on Earth shares DNA made from four different elements called nuclear bases. These are adenine (A), cytosine (C), guanine (G), and thymine (T). All the complexity of life ever to spring up on this fair planet was borne out of different re-arrangements of these four. Not only can we re-arrange the letters that tell life how to be alive, but now, we can introduce our own symbols in there.

Today, another team from the same institution published a paper that could create a paradigm shift in how we interact with life’s fundamental building blocks. They report that life understands the synthetic nucleotides embedded in DNA.

CTAG-XY

The team first snuck the two additional ‘letters’, X and Y,  into the genome of an E. coli bacterium strain back in 2014. However, the organism was highly unstable. It could maintain X and Y in its genome while going about its daily business, not so much during cell division. Which is a problem when you’re gene-shaping.

“Your genome isn’t just stable for a day,” senior researcher Floyd Romesberg explained earlier in the year. “Your genome has to be stable for the scale of your lifetime. If the semisynthetic organism is going to really be an organism, it has to be able to stably maintain that information.”

Subsequent refining of the organism, including switching to a new nucleotide transporter that would enable more stable DNA replication, a re-design of the Y base, and better delivery through the use of CRISPR-Cas9, allowed it to remain stable even through division.

Now, a paper describing further improvements brought to the organism’s stability comes to expand on that work. Romesberg and his colleagues started by embedding their unnatural bases in genes that also contained A, C, G and T. They found that within the semi-synthetic organism, these genes could be successfully transcribed into RNA molecules also containing the unnatural bases. The cells could then use these RNA molecules at their ribosomes (protein manufacturing plants) to direct the incorporation of unnatural amino acids into proteins.

Fluorescent E. coli.

The fluorescent protein in these bacteria is encoded by artificial DNA bases.
Image credits Yorke Zhang et al., 2017, Nature.

Scientists demonstrated this new transcription process in the E. coli strain, successfully transcribing its artificial X and Y nucleotides into biochemical compounds with the same efficiency it would for natural A, C, G, or T bases. This means that the bacterium could synthesize products containing non-canonical amino acids (ncAAs), compounds encoded by stretches of DNA containing Y and X. Its the first organism to both contain unnatural bases in its DNA and use the bases to instruct cells to make a new protein.

The synthesis process also hints at a new way of replicating molecules that rely to a lesser extent on hydrogen bonds (the type of electrochemical interactions which form the ‘rungs’ in DNA).

“Remarkably, this reveals that for every step of information storage and retrieval, hydrogen bonds, so obviously central to the natural base pairs, may at least in part be replaced with complementary packing and hydrophobic forces,” the team explains in the paper. “Despite their novel mechanism of decoding, the unnatural codons can be decoded as efficiently as their fully natural counterparts.”

The result of this process is a new class of semi-synthetical proteins — compounds we’ve never before seen in natural systems. What sets them apart is their incorporation of the unnatural base pair (UBP), the team writes, while retaining high stability. The four natural DNA bases code 20 amino acids. With the addition of X and Y, an organism could code for up to 152 new amino acids. The researchers hope these amino acids could become building blocks for new medicines.

“We have examined the decoding of only two unnatural codons, but the UBP is unlikely to be limited to these,” the researchers explain. “Thus, the reported SSI is likely to be just the first of a new form of semi-synthetic life that is able to access a broad range of forms and functions not available to natural organisms.”

It’s still unknown where this breakthrough will lead — what’s sure for now is that DNA on Earth just got a major update to its complexity.

The paper “A semi-synthetic organism that stores and retrieves increased genetic information” has been published in the journal Nature.

International Space Station

Bacteria shapeshift in space in response to antibiotics, becoming far more resilient

A rather distressing new study found bacteria cultured in microgravity exposed to common antibiotics responded radically different than here on Earth. Researchers report the bacteria essentially shapeshifted, growing smaller cell volumes and thicker membranes, which made them far more resilient. This raises multiple concerns if humanity is ever to become an interstellar space faring species.

International Space Station

Credit: NASA.

The E. coli bacteria were sent to the International Space Station in 2014 as part of an experimental project headed by CU Boulder’s BioServe Space Technologies. For two days, astronauts on board the station used high-tech incubators and test tubes to initiate the experiment. It was then sent on a commercial SpaceX Dragon spacecraft several months later.

During the experiment, several different concentrations of the antibiotic gentamicin sulfate were thrown at the bacterial cultures. This is a drug that kills them easily on Earth. In the near weightlessness of the ISS, however, these puppies proved far more resilient. 

Tests showed a 13-fold increase in cell numbers and a 73 percent reduction in cell volume size compared to an Earth control group. The paper published in Frontiers in Microbiology went on to trace other startling cellular differentiations. For one, the bacterial cell envelope — comprised of the cell wall and outer membrane — became thicker, offering the bacteria enhanced protection against the antibiotic. Secondly, the space-borne bacteria tended to grow in clumps. This way, the outer bacterial cells acted like a shield for the inner cells, enhancing the survivability of the bacterial culture at large.

In space, there are no gravity-driven forces like buoyancy and sedimentation. The only way drugs can interact with bacteria is through natural diffusion. As such, when the E. coli drastically shrank, the antibiotic-bacteria surface interface drastically decreased as well.

What’s more, the bacteria also grew outer membrane vesicles—small capsules that form outside the cell walls and act as messengers for cells to communicate with each other. When these vesicles pass a certain threshold, the bacterial cells can initiate the infection process.

“We knew bacteria behave differently in space and that it takes higher concentrations of antibiotics to kill them,” said lead autho Luis Zea, a BioServe Research Associate. “What’s new is that we conducted a systematic analysis of the changing physical appearance of the bacteria during the experiments.”

bacteria-iss

After being exposed to antibiotics, E. coli bacterial cells shrank but their walls hardened. Credit: Frontiers in Microbiology.

“Both the increase in cell envelope thickness and in the outer membrane vesicles may be indicative of drug resistance mechanisms being activated in the spaceflight samples,” said Zea. “And this experiment and others like it give us the opportunity to better understand how bacteria become resistant to antibiotics here on Earth.”

If bacteria are indeed harder to crack in outer space, we have a problem. Where humans go, bacteria follow closely — inside our guts even, where they outnumber somatic cells at least ten to one. If astronauts get sick, common antibiotics might not respond. People might die.

Research such as this is thus of the utmost importance for future space travel. By understanding how bacteria react with other organisms and antibiotics, we might one day find the safest course of action to travel to Mars and, hopefully, out of the solar system.

It’s becoming increasingly clear, however, that interplanetary travel will be no piece of cake for humans. We have to worry about radiation, the effects of weightlessness on the body and, not least, extremely resilient bacteria. Many biological processes which are very clear and predictable here on Earth become nebulous in space. It’s really a new frontier in science and we must be up to the challenge.

For the first time, researchers create “semi-synthetic” life form with man-made DNA

Researchers have created the first stable semi-synthetic life, a strain of E. coli bacteria with two extra artificial nucleotides in its genetic code.

Nucleotide chain at the “Miraikan” / The National Museum of Emerging Science and Innovation.
Image credits Miki Yoshihito / Flickr.

You, me, your pets, potatoes, coffee, basically all living things you can think of have one thing in common: the DNA that tells their cells what to do is encoded using only four bases. If you compare DNA to an instruction manual, nucleotides (or bases) would be the letters that make up words. In fact, we even represent them as letters — G, T, C, and A.

Pimp my DNA

You might have noticed that there’s only 4 of them. Which isn’t a lot. That’s why scientists have been toying around with the idea of adding extra letters to DNA for some time now.

It all started in 2014, when a team from the Scripps Research Institute in California successfully added synthetic nucelotides to a living organism’s DNA for the first time, creating so called semi-synthetic life. Their initial cultures were really bad at not dying, however. The team has spent two years refining the process, and has recently reported the creation of stable semi-synthetic organisms.

Their modified E. coli bacteria’s genetic code has two additional bases, X and Y, peppered throughout their DNA. The strain does not reject the X and Y bases and retains them in the genome for life. This achievement has incredible potential, as researchers can now tell cells what to do directly instead of rummaging around DNA strands for bits of code and being limited to natural processes.

“With the virtually unrestricted ability to maintain increased information, the optimised semi-synthetic organism now provides a suitable platform [to create] organisms with wholly unnatural attributes and traits not found elsewhere in nature,” the paper reads.

“This semi-synthetic organism constitutes a stable form of semi-synthetic life, and lays the foundation for efforts to impart life with new forms and functions.”

Bases for life

The team’s initial cultures weren’t viable as organisms. The main problems were that the cultures were weak and sickly compared to natural strains of E. coli, and that they couldn’t reliably replicate X and Y bases during division so their DNA often fractured during the process.

“If the semisynthetic organism is going to really be an organism, it has to be able to stably maintain [genetic] information,” said TSRI Professor and team leader Floyd Romsberg.

The team started by tweaking the nucelotide transport process, which inserts synthetic bases in the right spots of the bacterial genome. Their first transporter molecule was toxic to the bacteria, so it was altered until the cells showed no adverse reaction. Next, they changed the chemistry of the Y base so it was more easily recognized by the enzymes that power DNA replication during division. The last step was to use CRISPR-Cas9 to nudge  E. coli into considering the artificial bases as a natural part of their genome.

CRISPR-Cas9 is widely used as a genome-editing tool today, but it is originally a bacterial defensive mechanism. When encountering a new threat, such as a virus, bacteria take fragments of its genome and grafts it into their own DNA. Though foreign in nature, these pieces of code are treated as belonging to the bacteria. If the invader returns, these bits are used to create enzymes to attack them. The team programmed the semi-synthetic E. coli to treat genetic sequences without X and Y as a threat, meaning that any cells which lost them during replication were attacked.

Using the new methods, they were able to engineer stable E. coli cells. The bacteria are healthier and more autonomous than before. They also kept their artificial bases for 60 division cycles, so the team considers they an likely keep their genome make-up indefinitely.

Genetic gibberish

 

Each natural nucleotide pair encodes a different instruction. But cells don’t understand X and Y bases.
Image via Pixabay.

Right now, the X and Y bases don’t actually do anything. The pair they form doesn’t mean anything from the cell’s point of view — it doesn’t encode any information for the bacteria to use. Basically, they just take up space in the genome. In fact, they’re so foreign the bacteria don’t even know how to make more — the team has to supply X and Y for each division cycle.

As a proof of concept however, it shows that artificial bases can be grafted into a living organism and made to stick. The team will have to insert a gene that is actually readable for the bacteria to start using it.

Because X and Y are nothing like what nature has used up to now, Romsberg advises against panic that the semi-synthetic bug will evolve and wipe us out.

“Evolution works by starting with something close, and then changing what it can do in small steps,” Romesberg told Ian Sample at The Guardian.

“Our X and Y are unlike natural DNA, so nature has nothing close to start with. We have shown many times that when you do not provide X and Y, the cells die, every time.”

Having the ability to program cells to produce exotic proteins is the cornerstone in producing a huge range of new drugs. Alternatively, the E. coli can be used to produce novel materials, store information, and much more.

The full paper “A semi-synthetic organism with an expanded genetic alphabet” has been published in the journal PNAS.

Scientists coax bacteria towards silicon-based life

Life — from what we know so far, it takes some carbon, some water, and a dash of other elements to make it happen. We’ve never seen it form from anything else, no matter where we’re searched. And yet, there is one element found in abundance on Earth that biological life makes surprisingly little use of: silicon.

martian

Image credits Gomez Santos / Pixabay.

Silicon is very similar in its chemical make-up to carbon, and shares its tetravalence — each atom can bond to four other atoms — meaning silicon could, in theory, form the basis for complex molecules fundamental to life — such as proteins and DNA. Organic carbon-silicone bonds have been used by chemists for decades now in anything from paints to computer hardware. But these are produced artificially, and we’ve yet to see similar bonds pop up in nature. No silicon-based life has evolved on the planet, which is only stranger when you factor in that after oxygen, silicon is the most bountiful element in the Earth’s crust.

This has left scientists with a dilemma for decades now: is silicon-based life possible, and if so, what would it look like?

To try and answer that question, a team from the California Institute of Technology, Pasadena, has managed to coax living cells into forming carbon-silicon bonds, showing for the first time how nature can incorporate this element into the basic building blocks of life.

“No living organism is known to put silicon-carbon bonds together, even though silicon is so abundant, all around us, in rocks and all over the beach,” says one of the researchers, Jennifer Kan from Caltech.

The team started by isolating a protein that occurs naturally in Rhodothermus marinus, a bacterium which inhabits Iceland’s hot springs. Known as a cytochrome c enzyme, the protein’s main role is to shuttle electrons through the cells. The team chose it because lab tests showed that it could help create the kind of bonds used to hook carbon and silicon atoms together.

After identifying the gene that codes cytochrome c, they pasted it into a culture of E. coli bacteria to see if it would lead to the creation of those bonds. The first few tries didn’t result in much progress, but the team kept altering the protein gene within a specific area of the E. coli‘s genome until they finally achieved their goal.

“After three rounds of mutations, the protein could bond silicon to carbon 15 times more efficiently than any synthetic catalyst,” Aviva Rutkin reports for New Scientist.

This new method of trying the two elements together (with much greater efficiency than before) could change the way we think about producing the goods that require them, such as fuels, pharmaceuticals, or agricultural fertilizers. It also shows that life could (at least in part) be based on silicon.

“This study shows how quickly nature can adapt to new challenges,” one of the team, Frances Arnold, said in a press statement.

“The DNA-encoded catalytic machinery of the cell can rapidly learn to promote new chemical reactions when we provide new reagents and the appropriate incentive in the form of artificial selection. Nature could have done this herself if she cared to.”

Kan’s team had to really push the cells to create the bonds — this wasn’t something they were easily capable of doing on their own, or even very willing. Still, if the team continues to work with these kinds of bacteria, we could get an even better understanding of how life based on silicon might look like.

The full paper “Directed evolution of cytochrome c for carbon–silicon bond formation: Bringing silicon to life” has been published in the journal Science.

 

bacteria spreading agar

Scientists film bacteria becoming virtually drug-immune — and it took them only 10 days

Researchers mixed Hollywoodian magic with science to create a striking — and worrying — demonstration of how bacteria encounter, adapt, and finally thrive even in the presence of antibiotics.

bacteria spreading agar

Credit: Harvard Medical School

Acquired drug resistance is rapidly becoming a problem for medicine — germs adapt to our medicine much faster than we can develop and distribute new ones. But exactly how fast this adaptive process takes place isn’t really something people realize. A new Harvard Medical School and Technion-Israel Institute of Technology experiment, inspired by Hollywood’s tv-magic, offers the first large-scale example of how fast bacteria evolve to deal even with immense concentrations of antibiotics.

“It’s a powerful illustration of how easy it is for bacteria to become resistant to antibiotics”

The experiment consisted of placing the bacterium Escherichia coli in a huge 2-by-4-foot petri dish filled with agar (the jelly-like material used to nurture bacterial colonies in the lab). The team then divided this area into seven sections and treated them with various doses of medicine. The outermost slices were drug-free, followed by slices with just enough antibiotics to kill the bacteria. Each section that followed would receive a ten-fold increase in dose, so the middle area contained 1,000 times the minimum required concentration. Dubbed the MEGA (Microbial Evolution and Growth Area) plate, the design represents a more realistic environment to study how species overcome the spatial and evolutionary challenges that drive evolution, the researchers said.

“We know quite a bit about the internal defense mechanisms bacteria use to evade antibiotics but we don’t really know much about their physical movements across space as they adapt to survive in different environments,” said study first author Michael Baym, a research fellow in systems biology at HMS.

The team pointed a camera at the MEGA plate and took snaps of the colonies over the next two weeks. The time-lapse they made with these snaps is a powerful display of evolution at work — and a bone-chilling reminder of just how flimsy our drugs are against pathogens.

This plate isn’t a perfect illustration of how bacteria behave in the real world — in hospitals for example — but it does mimic them more closely than a traditional petri dish. This is because in bacterial evolution, space, size, and geography play a hugely important role, the team explains. Just like walking on a paved street is different from hiking in rough terrain for us, expanding in environments with varying antibiotic properties in the wild or in homogeneous settings in the lab are two very different things if you’re a bacteria.

The experiment proposes to teach HMS students about evolution in an engaging and visually captivating way. Senior study investigator Roy Kishony of HMS and Technion say the inspiration came from a digital billboard for the 2011 film Contagion. It showed a giant lab dish where glowing microbes crept slowly over a darker background to spell out the movie’s title.

“This project was fun and joyful throughout,” Kishony said. “Seeing the bacteria spread for the first time was a thrill. Our MEGA-plate takes complex, often obscure, concepts in evolution, such as mutation selection, lineages, parallel evolution and clonal interference, and provides a visual seeing-is-believing demonstration of these otherwise vague ideas. It’s also a powerful illustration of how easy it is for bacteria to become resistant to antibiotics.”

Postdoctoral research fellow at MIT and co-investigator Tami Lieberman, who was a graduate student in the Kishony lab at the time of the experiment, says the images captivate laymen and trained professionals alike.

“This is a stunning demonstration of how quickly microbes evolve,” she said.

“When shown the video, evolutionary biologists immediately recognize concepts they’ve thought about in the abstract, while nonspecialists immediately begin to ask really good questions.”

Spreading the news

Image credits NIAID / Flickr.

The experiment also allows us insight into how bacteria adapted to environmental constraints — in this case, increasingly deadly concentrations of drugs:

Bacteria first spread until they reached a concentration (antibiotic dose) in which they could no longer survive. A small number of individuals would eventually acquire resistance to the higher concentration through successive genetic changes. These mutants’ descendants migrated in the new area, competing with other resistant strains. The winning strains progressed to the area with the higher drug dose, until they again reached a drug concentration at which they could not survive.

Through small increments, non-resistant bacteria gave rise to moderately then highly resistant mutants. In just 10 days, the culture spawned mutants capable of surviving 1,000 times the dose of antibiotic trimethoprim that was deadly to the initial bacteria. When researchers used another antibiotic — ciprofloxacin — bacteria adapted to 100,000 times the initial deadly dose.

These mutations initially stiffen the bacteria’s growth rate — suggesting that while adapting to the dose, bacterias still found it hard to develop. Once fully resistant to the drug, they regained their normal growth rates.

The most resistant strains weren’t always the first to expand. Sometimes, they lagged behind weaker strains as they were developing into areas with higher doses of antibiotics. This goes against the commonly held belief that only the most resistant mutants survive high concentrations of a drug.

“What we saw suggests that evolution is not always led by the most resistant mutants,” Baym said. “Sometimes it favors the first to get there. The strongest mutants are, in fact, often moving behind more vulnerable strains. Who gets there first may be predicated on proximity rather than mutation strength.”

The full paper “Spatiotemporal microbial evolution on antibiotic landscapes,” has been published in the journal Science.

Untreatable bacteria identified in the US

A strain of E. coli resistant to last-resort antibiotics has been identified on United States soil for the first time. Health officials say this could be “the end of the road for antibiotics,” leaving us virtually helpless in fighting future infections.

Last month, researchers identified a 49-year-old Pennsylvania woman as the carrier for a strain of E. coli resistant to the antibiotic Colistin. The woman visited a clinic in Pennsylvania, which forwarded a sample to Walter Reed National Military Medical Center. Walter Reed found the bacteria in her urine.

Think of this drug as our nuclear option — it’s employed for particularly dangerous pathogens, when every other drug fails. This includes the CRE family, a group of germs so resilient and deadly that health officials have dubbed it “nightmare bacteria”. Infection with these superbugs ends up killing up to 50 percent of patients in some instances, and the CDC lists them among the country’s most urgent public health threats.

Finding a bug that can shrug off even Colistin on home soil “heralds the emergence of a truly pan-drug resistant bacteria,” say the authors of the paper detailing the discovery.

“It basically shows us that the end of the road isn’t very far away for antibiotics — that we may be in a situation where we have patients in our intensive-care units, or patients getting urinary tract infections for which we do not have antibiotics,” CDC Director Tom Frieden said in an interview Thursday.

This is the first known carrier of a Colistin-resistant strain in the United States. Last November, a report by Chinese and British researchers who found the Colistin-proof strain in pigs, raw pork meat and several people in China was met with shock by public health officials worldwide. The deadly strain was later discovered in Europe and elsewhere.

Escherichia coli (E. coli) naturally occurs in your gut and most strains are harmless. Some, however, can cause food-borne diseases with fever, nausea and vomiting to bloody diarrhea. The infections are transmitted by eating or drinking contaminated food and water. E. coli resistance for a spectrum of drugs has been increasingly reported in cases of urinary tract infections, and the WHO warns that the most widely used oral treatment — fluoroquinolones — are rapidly becoming ineffective. Seeing strains develop virtual immunity to any of our antibiotics is very bad news, Frieden says.

“I’ve been there for TB patients. I’ve cared for patients for whom there are no drugs left. It is a feeling of such horror and helplessness,” he added. “This is not where we need to be.”

The CDC and the Pennsylvania State Health Department mobilized immediately to investigate the case and to trace the patient’s contacts to see if the bacteria had spread. The CDC also said it is looking for other potential cases in the healthcare facility the patient visited.

The full paper, titled “Colistin resistance in the USA” has been published online in the journal Antimicrobial Agents and Chemotherapy and can be read here.

Scientists engineer first living organism with unnatural DNA

The entire living world is “written” with just four DNA bases:

  • A = adenine
  • C = cytosine
  • G = guanine
  • T = thymine

However, for the first time, researchers have now created a living cell with an added pair of DNA “letters,” or bases, not found in nature – the DNA alphabet just got some new letters!

“Life on Earth in all its diversity is encoded by only two pairs of DNA bases, A-T and C-G, and what we’ve made is an organism that stably contains those two plus a third, unnatural pair of bases,” said TSRI Associate Professor Floyd E. Romesberg, who led the research team. “This shows that other solutions to storing information are possible and, of course, takes us closer to an expanded-DNA biology that will have many exciting applications—from new medicines to new kinds of nanotechnology.”

Indeed, this is a monumental breakthrough, which could have potential applications in developing drugs and other useful biomolecules, paving the way for engineering new cells with new purposes.

DNA in a test tube

Via Synthorx.

Scientists have toyed with the idea of developing new DNA for decades, but it wasn’t until 1989 when Steven Benner, then at the Swiss Federal Institute of Technology in Zurich, developed the first non-natural pair of DNA bases in a test tube. But the DNA developed by Romesberg’s team is even more alien, but at the same time, resembles ACGT more. They identified a pair of bases, known as d5SICS and dNaM, that looked promising – the biggest challenge was to make them compatible with enzymatic machinery that copies and translates DNA.

“We didn’t even think back then that we could move into an organism with this base pair,” says Denis Malyshev, a former graduate student in Romesberg’s lab who is first author of the new paper. Working with test-tube reactions, the scientists succeeded in getting their unnatural base pair to copy itself and be transcribed into RNA, which required the bases to be recognized by enzymes that had evolved to use A, T, C and G.

Moving on to real organisms

So what researchers did was to take E. coli and modify it. Before they got E. coli to actually start replicating the DNA itself, they first had to supply the molecular building blocks artificially, by adding them to the fluid solution outside the cell. Then, they had to find special triphosphate transporter molecules to transport the DNA into the E. coli – basically, they added the transporter molecules into algae, and they fed the bacteria the algae.

“That was a big breakthrough for us—an enabling breakthrough,” said Malyshev.

Even after they figured out the transport mechanism, it took a whole year of figuring out problems and surpassing hurdles, but after that, it worked – the DNA was replicating on its own!

“When we stopped the flow of the unnatural triphosphate building blocks into the cells, the replacement of d5SICS–dNaM with natural base pairs was very nicely correlated with the cell replication itself—there didn’t seem to be other factors excising the unnatural base pairs from the DNA,” Malyshev said. “An important thing to note is that these two breakthroughs also provide control over the system. Our new bases can only get into the cell if we turn on the ‘base transporter’ protein. Without this transporter or when new bases are not provided, the cell will revert back to A, T, G, C, and the d5SICS and dNaM will disappear from the genome.”

A big leap, a reason to worry?

Maybe sci-fi fans will feel a little anxious here – I mean, developing unnatural DNA in a bacterium and feeding it algae… that sounds like a recipe for disaster, right ? However, there is no reason to worry. First of all, we’re talking about the controlled environment of a lab – at the first sign of possible unwanted contamination, the project will be certainly stopped. Second of all, these new base pairs of DNA do not code for anything. That can transcribe to RNA, but not to the transfer RNA that actually links the base pairs with amino acids. They can not create new proteins, they could not implement new information. In theory combined with other biotechnologies, it could do that, but it’s premature and unwarranted to talk about that.

For now, this is simply a groundbreaking discovery!

“Many in the broader community thought that Floyd’s result would be impossible,” says Benner, because chemical reactions involving DNA, such as replication, need to be exquisitely sensitive to avoid mutation.

Scientific Reference: A semi-synthetic organism with an expanded genetic alphabet. Nature (2014) doi:10.1038/nature13314

Microscale electric field gradients can tell the difference between good and bad bacteria in minutes from extremely small samples. Photo: Paul V. Jones

Device identifies and sorts bad germs from the good ones in minutes, instead of days

Your gut is home to some 100 trillion bacteria – more than the entire number of cells in the whole human body. Clearly, bacteria are fond of human intestines, as we humans, unknowingly or not, are fond of them. After all, without bacteria our organisms would be deprived of extremely vital vitamin sources and digestion aids. However, not all bacteria are beneficial – some, of course, are detrimental to human health and can cause death. Diagnosing bad bacteria infection is currently a laborious, lengthy and expensive process. A new device developed by scientists at Arizona State University’s Department of Chemistry and Biochemistry seeks to address this issue by significantly speeding up harmful bacteria identification.  Hopefully, in the next phase the researchers will turn the device portable, so that doctors as well as anyone else for that matter may run a quick check for bad bacteria effortlessly.

Microscale electric field gradients   can tell the difference between good and bad bacteria in minutes from extremely small samples. Photo: Paul V. Jones

Microscale electric field gradients can tell the difference between good and bad bacteria in minutes from extremely small samples. Photo: Paul V. Jones

One of the most common gut bacteria is the E. coli, which for the most part is beneficial for the organism producing K2 vitamins and preventing the establishment of pathogenic bacteria. Some E. coli strains, however, are harmful like the O157:H7 E. coli strain which is responsible every year for  2,000 hospitalizations and 60 deaths in the U.S. alone. Bacterial diagnosis typically involves collecting a culture sample either from food or infected patients, after which lab analysis is performed. Usually this takes a few days to make and is costly.

[ALSO READ] How bacteria colonize the human gut – study reveals important insights

Researchers at Arizona State University believe they have found a solution that could be used to easily and cheaply diagnose bad bacteria in a matter of minutes, instead of days. Inside a polymer chip, a saw-toothed microchannel concentrates and sorts microorganisms inserted inside based on their electrical properties. All forms of matter, including bacteria, have their unique electrical properties and simply by studying their electrical response researchers can tell what kind of bacteria they’re dealing with.

Sorting out germs

For their device, the Arizona researchers  used an ordinary strain of E. coli along with two pathogenic varieties. They injected the cells into each channel and simply applied voltage to drive the cells downstream. The geometric features of the channel shape the electric field, creating regions of different intensity.  This field creates what’s called a dielectrophoretic force which traps certain kinds of bacteria around the channel based on their molecular and electrical properties. During their demonstration, the team led by Professor Mark Hayes, separated extremely similar bacteria—pathogenic and nonpathogenic strains within the single species, E. coli.

“The fact that we can distinguish such similar bacteria has significant implications for doctors and health officials,” says Hayes. He explains, “that scientists have struggled to find ways to rapidly identify bacteria. E. coli O157:H7 is very similar in size and shape to other subtypes of the bacteria. But unlike many of the others it has the ability to produce shiga-like toxin, a protein that breaks down blood vessel walls in the digestive tract.”

It’s important to mention that the device worked with pure cultures. Obviously, in the real world when you carry out a sample it will be filled with all kinds of impurities. The researchers plan to tackle this with their next version which should be able to accurately detect bacteria in a complex mixture. Also, making the device portable is a big goal.

The device was described in a paper published in the journal Analytical and Bioanalytical Chemistry.

Researcher finds new immune system in mucus

Think about mucus – what comes to mind? It’s slimy, it’s gross, no one really likes it, right? Well, as a team from San Diego State University showed, mucus is also home to a very powerful immune system that has the possibility to change the way doctors treat a number of diseases.

Bacteriophages are basically viruses that infect and replicates within bacteria. The research addressed all sorts of animals, from sea anemones to mice and humans, and found that bacteriophages adhere to the mucus of all of them. They placed bacteriophage on top of a layer of mucus-producing tissue and observed that the bacteriophage formed bonds with sugars within the mucus, adhering to its surface every single time.

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They then challenged them by injecting E. Coli in the mucus, and they found that the bacteriophage attacked and killed off the E. coli in the mucus, effectively forming an anti-microbial barrier protecting the host from infection and disease.

In order to test their discovery, they then conducted parallel research on non-mucus producing cells, infecting them with E. Coli, in the same fashion. The results were disastrous for the cells.

“Taking previous research into consideration, we are able to propose the Bacteriophage Adherence to Mucus — or BAM — is a new model of immunity, which emphasizes the important role bacteriophage play in protecting the body from invading pathogens,” Barr said.

But what makes this finding really special is that that the bacteriophage are already present on all humans and animals; they are recruited almost as mercenaries by cells who support them and then act as protectors to the host, attacking invaders on their own.

“The research could be applied to any mucosal surface,” Barr said. “We envision BAM influencing the prevention and treatment of mucosal infections seen in the gut and lungs, having applications for phage therapy and even directly interacting with the human immune system.”

Research paper.

ecoli

Is evolution predictable? Research shows specialization isn’t that special after all

There are millions of species on Earth, and naturally understanding the mechanics of evolution is of great importance for understanding further on what sparks life. What sparks consciousness, well that’s a whole different ball-game. Currently, scientists are concentrating on how diversification occurs in order to better their knowledge of how so many species surfaced along the eons. Is this task impossible though? Is evolution itself predictable?

ecoli

The E. coli bacteria. (c) Food Poison Journal

A recent research by scientists at University of British Columbia seems to suggests so, after they breaded three separate populations of the popular lab pet bacteria, E. coli, for a whooping 1200 generations. What they found is that eventually each population, though separate and independent from each other, evolved in very similar and in some respects identical strains to accommodate to their new environments.

Conducted by Matthew Herron and Michael Doebeli, the experiment involved placing each of the E. coli populations in an environment with two different sources of dietary carbon – glucose and acetate. In the beginning all bacteria behaved as generalists, after some 1200 generations though the bacteria branched into two distinct species, each specialized on eating one of the two food sources. This happened in each of the three separate populations.

Simple empirical observations weren’t enough, so prudent as they are, the scientists were careful to freeze samples from each population at 16 different points during their evolution. Recent advances in sequencing technology allowed the scientists to sequence large numbers of whole bacterial genomes, so the researchers had now access to a large volume of highly valuable data.

What they found was absolutely striking similarities in how the bacteria evolved. Basically, for all populations a core set of genes were causing the two different phenotypes that they saw, and in some cases the researchers witnessed the very same exact genetic change at play.

“There are about 4.5 million nucleotides in the E. coli genome,” said co-author Matthew Herron, research assistant professor at the University of Montana. “Finding in four cases that the exact same change had happened independently in different populations was intriguing.”

The obvious conclusion: selection can be deterministic.

“Not only did similar genetic changes occur, but the temporal sequence in which the changes occur over evolutionary time was also similar between the different evolving populations. This ‘parallelism’ implies that diversification is a deterministic process driven by natural selection,” said co-author and University of British Columbia zoologist Prof. Michael Doebeli.

The authors claim that negative frequency dependence – a well known particular form of selection – plays a major role in driving diversification. Simply put, a bacteria specialized on feeding on an alternative resource will be at an advantage, and thus have greater chances of passing its genes.

Is this research flawed, however? Considering the study only focuses on only a single type of bacteria, this might be the case. Evolution is not simple, by any means, and despite it might be governed by a fixed set of laws, the fabrics of its creation can be rather startling.

Nevertheless, the authors plan on repeating the experiment and conduct other more in order to see whether these conclusions remain the same at a larger scale and with larger, more complicated organisms.

Findings were published in the  journal PLOS Biology.

Bacteria replicate close to the limit of thermodynamic efficiency

We often like to think us humans have achieved a remarkable standard of efficiency and development – but a look at the animal life around us is often enough to humble us.

Replicating bacteria and physics

The common gut bacteria, Escherichia coli (E. coli, in short) typically takes about 20 minutes to duplicate itself in good conditions – a staggering rate, but could it do any faster? According to researchers it could, but only a little.

Jeremy England at the Massachusetts Institute of Technology in Cambridge estimates bacteria are impressively close to the limit imposed by replication thermodynamics – by only a factor of two or three.

“It is heartening to learn this”, says Gerald Joyce, a chemist at the Scripps Research Institute in La Jolla, California, who develops synthetic replicating molecules based on RNA. “I suppose I should take some comfort that our primitive RNA-based self-replicator apparently operates even closer to the thermodynamic lower bound”, he adds.

The study was motivated by a long lasting desire to blend thermodynamics with the living world, and an even more puzzling question, how do they seemingly defy the Second Law of thermodynamics, sustaining order instead of falling apart into entropic chaos?

Bio-thermodynamcs

Well the break of the law is only apparent: living organisms produce enough entropy through the form of heat to compensate for their own orderliness – which is why you’re hot when the outside temperature is the same as your own body (or even lower), because you need to release heat. England set out to thoroughly explain how much heat must unavoidably be produced by replication; in other words, how efficient can replication be, in respect to thermodynamics.

To tackle this issue, he used various complex concepts of statistical mechanics to figure out what is the cheapest way, in terms of energy, to go from one E. coli to two E. coli. In order to do this, the raw ingredients of the new cell have to be put in order, and that order has to be ‘paid’ with energy – pumping heat into the surrounding environment. In order to calculate the amount of energy, he first calculated how much energy has to be ‘paid’ in order to transform the raw ingredients (amino acids, for example) into cell parts. But this is just the first, easier part. Things get more complicated from now on.

He also had to figure out the impact of the chemical bonds tying the cell parts together as well as the number of bonds, as well as the other biological processes the bacteria undergoes. As an analogy, imagine building a car: it’s not enough to build the parts and put them in a room, you also have to assemble them in the right order and make sure the car will turn out fine.

This, in turn, can also be calculated by the reverse process: a second cell falling apart into its constituents. But this heats up the debate even more.

An entropic debate

The problem is, as England himself describes it, that “there are many ways of starting with two cells and ending up with one”, and not all are equally likely. The challenge, he explains, is to figure out “what class of paths should dominate that process”.

Determinining those “many ways” is the real problem here.

“You can drive yourself nuts trying to think of everything,” England says.

But he took the easy way out, considering the most general reversal route: he assumed that by chance, all the molecules in the replicated bacteria just disintegrated – something which of course is extremely unlikely. But by figuring out precisely how unlikely, England can place a rough limit on how reversible replication is, and thus on its minimum energy cost.

It’s this approach that has been deemed as irresponsible by other researchers.

“As an experimentalist, it is hard for me relate to this ‘spherical cow’ treatment of a self-replicating system,” Joyce says. “Here E. coli seems to be nothing more than the equivalent of its dry weight in proteins.”

The ‘spherical cow’ is a joke making fun of some researchers’ tendency to oversimplify facts and relations. But even so, Joyce agrees with England that bacteria could hardly to better, especially considering that they have to deal with different environments and they have to cope with every one of them. The study could have numerous ramifications in biotechnology, in the attempt to create modified bacteria.

Scientific source

Four genetic mutations in viruses like these two lambda viruses led them to find a new way to attack their bacterial hosts. (c) Center for Advanced Microscopy, MSU

Virus mutations shows natural selection theory at its best

Darwin’s theory of natural selection illustrates perfectly what evolution is all about, the survival of the fittest if you will. It’s because of natural selection that a crocodile has an armor-like skin to protect it against enemies, a chameleon can change its color and camouflage itself for protection and hunting or humans evolved a more potent brain, and brought us to the forefront of evolution on Earth. It’s pretty well understood how evolution works, but the mechanisms behind it not so well, how a new feature or treat appears across an entire species, and so on.

New research by scientists at Michigan State University has followed a virus called “Lambda” that mutated extremely quickly and developed the ability to infest a bacteria through a new doorway.  Normally, the Lambda virus is inherently capable of infesting E. coli cells through a receptor LamB, on the bacterium’s outer membrane. When cultured under certain conditions, however, the E. coli cells develop a natural resistance to the LamB virus, and no longer produce the LamB receptors.

Four genetic mutations in viruses like these two lambda viruses led them to find a new way to attack their bacterial hosts. (c) Center for Advanced Microscopy, MSU

Four genetic mutations in viruses like these two lambda viruses led them to find a new way to attack their bacterial hosts. (c) Center for Advanced Microscopy, MSU

In 25 of the 102 trials, the virus acquired the ability to infect bacteria through another receptor, called OmpF. The researchers looked at the genetic changes associated with this new ability and found that all the strains that could infect the bacteria shared at least four changes. The other 80 viruses that attempted to infect the bacteria also mutated, but the researchers found that all four mutations had to be shared as a sum and work together to enter the host.

“When you have three of the four mutations, the virus is still unable to infect (the E. coli),” Justin Meyer, the lead researcher and a graduate student at Michigan State University, said. “When you have four of four, they all interact with each other. … In this case, the sum is much more than its component parts.”

Interestingly enough, a few months ago scientists in the United States and the Netherlands produced a deadly version of the bird flu, a virus which currently is just five mutations away from becoming transmissible to humans. It’s highly unlikely, scientists believe, for bird flu to naturally acquire all the necessary mutations for human infestation all at once. However, if conditions are favorable step by step, the virus might eventually evolve sequentially.

Meyer’s “Lambda” research implies that adaptation by natural selection, or survival of the fittest, plays an important role in the evolution of a virus.

“In other words, natural selection promoted the virus’ evolution because the mutations helped them use both their old and new attacks,” Meyer explained.

”The finding raises questions of whether the five bird flu mutations may also have multiple functions, and could they evolve naturally?”

Transistor gates created out of E. Coli bacteria – huge biocomputing leap forward!

Scientists at London’s Imperial College have successfully managed to create biological logic gates, indispensible for the production of electronical devices, simply our of bacteria and DNA. Though the research detailed in a recently published study in the journal Nature Communications was anything but simple, it provides an incredible advancement in the field of biotechnology.

“Logic gates are the fundamental building blocks in silicon circuitry that our entire digital age is based on,” said Richard Kitney co-author of the research project recently published in the journal nature Communications. “Without them, we could not process digital information. Now that we have demonstrated that we can replicate these parts using bacteria and DNA, we hope that our work could lead to a new generation of biological processors, whose applications in information processing could be as important as their electronic equivalents.”

Scientists have expermentally proven that their that their biological gates can replicate the process that is equivalent to an electronic transistor gate that can be switched on and off. In one experimental instance, the team made an AND gate from E Coli bacteria, a keyword most of us link with an impending pandemic (there are numerous variants of the strain, few are indeed dangerous), which had its DNA altered to perform a switch on/off action when interacting with a certain chemical.

While these are the most advanced biological gates created so far, Kitney and his team aknowledge that they’re still very far away from presenting to the world a reliable product. The future, however, seems to shine for bio technology. Such bio processing units could be streamed through one’s arteries and monitor various parameters through biosensors. In case of misbalanced parameters, the biodevice might then trigger medication to relieve the affected area. Cancer cells could be pounded imediately before they have the chance to spread. The potential applications are too many to ennounce here, albeit still very far away from reality.

The next step in the development are multiple gates in “more complex circuitry”, which could one day lead to building blocks for “microscopic biological computers,” like the ones listed in the potential applications above. One step at a time.

The 100 Mb Ion 316 semiconductor sequencing chip released in July 2011

New DNA sequencing device could decode your genome for just $1000

The inventor Jonathan Rothberg with a semiconductor chip used in the Ion Torrent machine. (c) Christopher Capozziello , NY Times

The inventor Jonathan Rothberg with a semiconductor chip used in the Ion Torrent machine. (c) Christopher Capozziello , NY Times

News of a low-cost semiconductor-based gene sequencing machine has been reported this Wednesday in the journal Nature, by a team led by Jonathan Rothberg. The astonishing advancement might lead to a age of personal human genome sequence, where people will be able to decipher their own DNA for as low as $1000.

The human genome was first mapped in 2001 and cost roughly $1 billion to do. Now, ten years and other tens of billions of dollars later important advancements have led to further detailed research, like the sequencing of a complete neanderthal genome, as well as optimization of the process and technology employed so it might become cheaper and faster.

Inventor, Jonathan Rothberg of Ion Torrent Systems in Guilford, Conn., is one of several pursuing the goal of a $1,000 human genome, which he said he could reach by 2013 because his machine is rapidly being improved. To test their genome device, they chose to map the one of Intel’s co-founder, Gordon Moore, the man behind the famed “Moore’s Law” prediction of exponentially growing computer power.

“Gordon Moore worked out all the tricks that gave us modern semiconductors, so he should be the first person to be sequenced on a semiconductor,” Dr. Rothberg said.

The 100 Mb Ion 316 semiconductor sequencing chip released in July 2011

The 100 Mb Ion 316 semiconductor sequencing chip released in July 2011. (c) Ion Torrent

The technology employs semiconductor chip to sense DNA or genetic material by detecting a voltage change, instead of light. This eliminates the use of highly expensive equipment that would’ve been required otherwise. Using this tech, the evolution of which is compared by its researchers with that of the digital camera, scientists have been able to scan three bacterial strains and one human genome.

“When it [digital photography] first started out, the resolution was not good and the pictures were not as good as on film. But the technology improved, which made it more accessible and now more people can enjoy photography and become better photographers,” Dr. Maneesh Jain, vice president of marketing and business development at Ion Torrent said.

The human genome is that of Dr. Moore, as you’ve been given to find out earlier, and as for the bacterial strains, the first two genomes of the deadly E. coli bacteria that swept Europe in the spring were decoded on the company’s machines. The whole decoding process takes less than two hours to complete!

Applications, of course, are numerous especially for the common users. At $1000, a genome sequence might become as common as a medical check in the very close future. You’d then be confronted with your very own mapped genome, which when interpreted can describe various medical condition predispositions, leading to the so-called personalized medicine, which seeks to avoid trial-and-error by using genetic data found during a scan to better pair treatments with diseases.

Tell me what your genes are, so I can tell you who you are

Don’t expect everything you get back to be extremely accurate, though. Dr. Moore’s genome has a genetic variant that denotes a “56 percent chance of brown eyes,” one that indicates a “typical amount of freckling” and another that confers “moderately higher odds of smelling asparagus in one’s urine,” Dr. Rothberg and his colleagues reported. Also, Dr. Moore’s genome has two strains that seems to indicated towards an “increased risk of mental retardation” — which was obviously never the case.

Genetic hazards, however, come at a much lower stake than those caught up during one’s lifetime.

“Most of what genetics tell us is that there are a lot of fairly common variants that have a modest degree of risk for diseases,” Dr. Peter Gregersen, director of the Robert S. Boas Center for Genomics and Human Genetics at the Feinstein Institute for Medical Research in Manhasset, N.Y said. “This is important from a scientific point of view, but the data itself is not actionable.

“The risk of disease associated with high blood pressure, smoking and high cholesterol is far greater than most of the genetic risks coming out of whole genome scanning,” Gregersen added. For example, if your genome scan identified a mutation that put you at risk for macular degeneration, a leading cause of blindness, “you may see an ophthalmologist, and there are forms that are treatable, but knowing your genetics won’t impact this much,” he said.

More time, research and money is needed for a more useful information to be outputted by a genome sequencing machine, as the human DNA is decoded to a more precise degree. We might be headed towards Gattaca hell, a utopian/dystopian climate, depends on how you decide to favor it, where everything will be known about you before you’re even born – how you’ll look when you’re 25, how smart can you become, where you’d be best fitted for work, whether there’s a chance you’ll condone in criminal behavior, etc. It’s all in the genes my momma used to tell me…