Antibiotic resistance: How some bacteria acquire resistance genes from their environment?

Antibiotic resistance has made certain infections, sometimes common, such as urinary and respiratory infections, impossible to treat, representing a major setback in the medical care of human and animal patients. This resistance has thus become a major health issue, which has led the WHO (World Health Organization) to establish a list of bacteria in which antibiotic resistance is particularly worrying.In a new study published in the journal mBio, we focused on one of these bacteria that are particularly resistant to antibiotics, Acinetobacter baumannii. The latter is responsible for many opportunistic and nosocomial infections. We have determined the mechanisms that allow this bacterium to rapidly acquire resistance genes from neighboring bacteria.

The bacterium Acinetobacter baumannii is responsible for opportunistic infections (infections caused by germs that are usually not very pathogenic but that cause infections in people with a deficient immune system) and sometimes nosocomial infections (acquired in hospitals). A. baumannii infections are not very common but very difficult to treat. There are even cases of resistance to the last resort broad-spectrum antibiotics called carbapenems.
Resistance to several antibiotics (multi-resistance), when it includes resistance to carbapenems, has led the WHO to rank A. baumannii strains as priority in the search for new antibiotics.

Over the last decade, several genomic analyses of multi-resistant A. baumannii strains had indicated that the resistance genes, sometimes numerous, could be acquired from other bacteria of the same species or even from different species. The biological phenomenon at the origin of these gene transfer events remained to be determined. The study, co-authored by Maria-Halima Laaberki, lecturer at VetAgro Sup, and Xavier Charpentier, research director at Inserm and team leader at the International Centre for Infectious Diseases Research in Lyon (CIRI, CNRS/École Normale Supérieure de Lyon/INSERM/Université Claude Bernard Lyon 1), reveals the conditions in which these transfer events occur. Indeed, they demonstrate that a bacterium sensitive to an antibiotic is capable of acquiring the resistance of a neighboring bacterium in less than 4 hours, including resistance to carbapenems.

This active transfer, called natural transformation (discovered in 1928 by Frederick Griffith in pneumococcus and, since then, in many bacteria), occurs in the recipient bacteria, which is able to capture and incorporate into its genome the DNA of neighboring bacteria.

This transfer is extremely efficient and is obtained from small quantities of DNA naturally released by the resistant neighboring bacteria.

To obtain these results, the research team used both conventional and genome sequencing-based bacterial genetic techniques. The latter approach, used here as a transfer event mapping method, revealed that this bacterium is capable of acquiring more than 80 genes in a single transfer event. In a few hours, A. baumannii can thus modify more than 3% of its genome, giving it the ability to resist to many classes of antibiotics.

These results provide a better understanding of how this pathogen accumulates antibiotic resistance. In direct link with public health issues, the team is currently pursuing its research and working to determine in which environment this resistance is acquired and how to anticipate the appearance of new resistances.

This publication presents part of Anne-Sophie Godeux's university thesis on the emergence of resistance in A. baumannii, co-funded by VetAgro Sup and the LabEx ECOFECT supervised by Maria-Halima Laaberki.

Authors : Anne-Sophie Godeux, Elin Sveldhom, Samuel Barreto, Anaïs Potron, Samuel Venner, Xavier Charpentier, Maria-Halima Laaberki

Open access publication: https://doi.org/10.1128/mbio.02631-21

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Antibiotic resistance: How some bacteria acquire resistance genes from their environment?

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