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Type IV traffic ATPase TrwD as molecular target to inhibit bacterial conjugation

Abstract: Bacterial conjugation is the main mechanism responsible for the dissemination of antibiotic resistance genes. Hence, the search for specific conjugation inhibitors is paramount in the fight against the spread of these genes. In this pursuit, unsaturated fatty acids have been found to specifically inhibit bacterial conjugation. Despite the growing interest on these compounds, their mode of action and their specific target remain unknown. Here, we identified TrwD, a Type IV secretion traffic ATPase, as the molecular target for fatty acid-mediated inhibition of conjugation. Moreover, 2-alkynoic fatty acids, which are also potent inhibitors of bacterial conjugation, are also powerful inhibitors of the ATPase activity of TrwD. Characterization of the kinetic parameters of ATPase inhibition has led us to identify the catalytic mechanism by which fatty acids exert their activity. These results open a new avenue for the rational design of inhibitors of bacterial conjugation in the fight against the dissemination of antibiotic resistance genes.

 Authorship: Ripoll-Rozada J., García-Cazorla Y., Getino M., Machón C., Sanabria-Ríos D., de la Cruz F., Cabezón E., Arechaga I.,

 Fuente: Molecular Microbiology, 2016, 100(5), 912?921

 Publisher: John Wiley & Sons

 Year of publication: 2016

 No. of pages: 10

 Publication type: Article

 DOI: 10.1111/mmi.13359

 ISSN: 0950-382X,1365-2958

 Publication Url: https://doi.org/10.1111/mmi.13359

Authorship

YOLANDA GARCIA CAZORLA

MARIA GETINO REDONDO

CRISTINA MACHON SOBRADO

DAVID SANABRIA RIOS