Institut Pasteur researchers in the Antibacterial Agents Unit, directed by Patrice Courvalin, studied resistance to vancomycin in enterococcus bacteria and demonstrated why the mechanism of resistance to this antibiotic has spread so effectively throughout the world. It was previously believed that only large-scale antibiotic use would be responsible for the resistance spread. However, this study reveals that some resistance mechanisms are able to persist even if no antibiotics are present in the environment, and to spread even in their absence.
Paris, september 20, 2010
Researchers from the Antibacterial Agents Unit, directed by Patrice Courvalin, focused on the mechanism of resistance to vancomycin in enterococci, one of the main species responsible for nosocomial infections. In an article published in PNAS, the Institut Pasteur team explained why the genes responsible for resistance to this antibiotic have spread so effectively throughout the world. In recent decades, enterococci have developed multiple resistance, and vancomycin is a last-resort treatment.
The seven vancomycin resistance genes are carried by a mobile genetic element that can be transferred to other bacteria. When these genes are expressed, they cause the bacterial wall to be entirely remodeled. This confers to the bacteria a high level of resistance to vancomycin but also has a high fitness cost, slowing down bacterial growth.
In the present case, it would appear that in the absence of the antibiotic, this mechanism involves no fitness cost for the resistant bacteria since the resistance genes are only expressed when the bacteria are in the presence of the antibiotics. Both in vitro and in vivo, the resistant bacteria retain the same characteristics as their vancomycin-sensitive counterparts, whether in terms of growth rate, their ability to colonize an environment, or their capacity to spread.
The data obtained using clinical isolates and mutants constructed in vitro highlight a major problem in the fight against antibiotic resistance. It is the first demonstration of a complex and costly resistance mechanism that can operate in bacteria without putting them at a competitive disadvantage.
This observation will encourage researchers to strive for a better understanding of resistance mechanisms and their “biological cost” for the bacteria that host them. The Institut Pasteur team is continuing to explore these properties, particularly in the bacteria that cause nosocomial infections.
This work received funding from the European Commission.
Inducible expression eliminates the fitness cost of vancomycin resistance in enterococci, PNAS, vol 107, n° 39, p. 16964 – 16969, September 28, 2010.
Marie-Laure Foucault, Florence Depardieu, Patrice Courvalin, and Catherine Grillot-Courvalin
Antibacterial Agents Unit, Institut Pasteur, 75724 Paris Cedex 15, France
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