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Interview – antibiotic resistance: Toulouse researchers make a big discovery

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A Toulouse Research team has discovered a mechanism for antibiotics resistance Pseudomonas aeruginosaA particularly dangerous bacteria. This great progress, published in Journal of extracellular vesicles on January 22ndCould pave the way for new treatments.

Professor Éric Oswald, practitioner of the Toulouse University Hospital, returns to this discovery, the fruit of cooperation with many researchers, including Doulouse Doctoral Audrey Goman, the first author of the study.

Her study shows an unprecedented mechanism of antibiotic resistance. Can you explain your discovery to us?
We have examined a phenomenon of resistance in pseudomonas aeruginosa, a pathogenic bacteria that causes serious infections, especially in the hospital. We have identified the CPRA protein, which leads to a modification of the bacterial membrane under the effect of an antibiotic of the last way out. This modification promotes the production of toxic vesicles that increase both antibiotic resistance and the virulence of the bacteria.

How did you demonstrate the existence of this vesicle?
We have analyzed bacterial covering that means the liquids in which bacteria are cultivated and the presence of growth of bacterial membranes. We then cleaned this vesicle and proved that they were poisonous. We have also shown that your production was triggered by the presence of certain antibiotics.

This resistance to antibiotics therefore has a perverse effect: it worsens the infection?

Exactly. By modifying their membrane to protect itself, bacteria reinforce virulence. This phenomenon triggers an excessive inflammatory reaction in the patient, which further complicated medical care.

Does this discovery have an impact beyond pseudomonas aeruginosa?

Yes, and this is an essential aspect of our study. We have found similar mechanisms in other pathogenic bacteria, including certain managers of extra-intinal infections and even bacteria that attack plants. This means that this defense strategy is widespread in the world of bacteria and could affect many infections.

How can this discovery help combat bacterial infections?

It shows a potential goal for new treatments. Instead of attacking the bacteria directly with antibiotics, we were able to inhibit the production of this toxic vesicle and thus restrict both the antibiotic resistance and the virulence of the bacteria. This approach would restore the effectiveness of existing treatments.

Can we talk about great progress?

It is an important progress because it questions the classic vision of bacterial resistance. So far, this resistance has been regarded as a simple defense mechanism. However, we show that it is also associated with an increase in virulence. Our study has already sparked great interest in the scientific community and opens up the way to new research.

Resistance to antibiotics is a major problem in public health. Why is it so worrying?

Because it progresses at alarming speed. Who classifies certain resistant bacteria, including pseudomonas aeruginosa, to priority threats. These bacteria are responsible for many nosocomial infections, and their resistance significantly reduces the therapeutic options. If we do not find any solutions, we may be at a time after antibiotics in which banal infections become fatal.

Will bacteria not develop other resistance strategies with this threat?

It is an eternal breed. Bacteria develop and find new ways to constantly develop to escape the treatments. By better understanding of your adaptation mechanisms, we can predict these developments and develop strategies to limit the appearance of new resistance.

What are the tracks examined today to limit this resistance?

There are several approaches. Some aim to discover new antibiotics, others to develop alternative treatments such as phages. The improvement of the hygiene rules and reducing the abusive use of antibiotics also play a key role. Finally, vaccination against certain bacteria can help limit their spread.

Could your discovery on veterinary or agriculture be applied?

Quite. The bacterial resistance not only affects people, but also affects animals and plants. Our results could be used to develop new strategies against breeding or agricultural infections. For example, we are working on vaccinations with researchers who specialize in bird flu.

How long is this research necessary?

It is based on observations that were made about fifteen years ago. We have gradually accumulated information before we can clearly demonstrate this mechanism. This shows the nature of scientific research well: it is a long -term job based on successive discoveries.

How many researchers contributed to this study?

We were several teams, especially in Toulouse, Besançon and Marseille and in a laboratory in Japan. Research is a collaborative work: Each team has its specialist knowledge in order to promote the global understanding of the phenomenon.

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