Tag Archives: Escherichia

Escherichia Coli.

Researchers film bacteria sharing antibiotic resistance in real time — and find a potential fix

New research into how antibiotic resistance spreads among bacterial populations points the way forward to fighting this growing threat.

Escherichia Coli.

Escherichia Coli.
Image credits Gerd Altmann.

Growing levels of antibiotic resistance, both in scope and sheer effectiveness, is a very real threat for us. It’s easy, in this day and age, to consider most bacteria and the diseases they cause as simple nuisances. But that safety is owed to the antibiotics and active compounds we’ve developed to protect us — should they turn ineffective, we’re as much at the mercy of these germs as any other organism on the planet.

However, new research shows it isn’t unstoppable. Robust, yes; backed-up with redundancy systems, yes — but not unstoppable.

The tiny pump that could

The research was carried out by a team of researchers from the Université Lyon and CNRS, the French National Center for Scientific Research. They successfully filmed the process of antibiotic resistance acquisition in real time, thus finding a new and central player that takes part in this process.

Antibiotic resistance primarily spreads among bacteria through a process known as (bacterial) conjugation, which is basically the sharing of genetic material. Systematic genetic sequencing of both pathogenic and environmental strains of bacteria suggests that a very wide range of genetic elements can be shared via conjugation which encodes resistance to most or all of the antibiotic classes currently in use.

So we know how it goes down, but we’re still in the dark in regards to how long it takes for conjugation to work its magic and how antibiotics interfere with the process. That’s what the present research aimed to find out.

The team worked with a strain of Escherichia Coli (E.coli) bacteria resistant to tetracycline, a commonly used antibiotic. Tetracycline works by attaching itself to the bacteria’s molecular mechanisms, rendering them unable to produce proteins. The team exposed the bacteria to tetracycline in the presence of another strain that was not resistant to the substance. Previous research told the team that, in such conditions, the spread of antibiotic resistance hinges on the first strain clearing the drug out using “efflux pumps” on their membrane before it can wreak havoc internally, thus conferring them some degree of resistance to the drug.

The team reports seeing DNA transmission being carried out between individuals of the two strains with one specific efflux pump, the TetA pump. Using fluorescent marking and live-cell microscopy, the researchers tracked the spread the DNA encoding this pump from resistant bacteria and how the recipient ones expressed the genes.

It only took 1 to 2 hours for the single-stranded DNA fragments put out by the efflux pumps to be turned into a double-stranded DNA molecule and, subsequently, into a functional protein, they report. In effect, that is the timeframe required for resistance to spread between different strains of bacteria. You can see the process in the video below; green bacteria are the donors (i.e. resistant E.coli strain) and the red ones are the recipients. In effect, everything you see turning green is learning tetracycline resistance from its peers.


Given the way tetracycline works — by blocking the production of proteins — you’d reasonably expect it to block the ‘red’ bacteria from synthesizing TetA efflux pumps (they’re made of proteins). However, the team is surprised to report that this isn’t the case. Paradoxically, the bacteria were able to survive and develop a resistance to tetracycline even in the presence of this drug — which suggested there’s another, unknown factor at work here.

It seems to be another efflux pump, they explain. Called AcrAB-TolC (scientists are good with naming stuff), this pump is present in virtually all bacteria, but serves a general role. As such, it’s less efficient than TetA at ejecting tetracycline, but it is still able to remove a small quantity from the cell, allowing the bacteria to carry out a minimal level of protein synthesis. This process allows bacteria to become durably resistant to antibiotics should they be provided with the right genes from the environment.

However, the findings also point the way to a potential fix for acquired antibiotic resistance.

“We could even consider a therapy combining an antibiotic and a molecule able to inhibit this generalist pump,” says Christian Lesterlin, a researcher at Lyon’s Molecular Microbiology and Structural Biochemistry laboratory and the paper’s corresponding author.

“While it is still too soon to envisage the therapeutic application of such an inhibitor, numerous studies are currently being performed in this area given the possibility of reducing antibiotic resistance and preventing its spread to the various bacterial species.”

The paper “Role of AcrAB-TolC multidrug efflux pump in drug-resistance acquisition by plasmid transfer” has been published in the journal Science.