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Title

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

AuthorsRipoll-Rozada, Jorge ; García-Cazorla, Yolanda; Getino, María; Machón, Cristina ; Machón, Cristina ; Sanabria-Ríos, David J.; Cruz, Fernando de la ; Cabezón, Elena ; Arechaga, Ignacio
Issue Date2016
PublisherWiley-Blackwell
CitationMolecular Microbiology 100(5): 912-921 (2016)
AbstractBacterial 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. Antibiotic resistance is an emergent threat to human health. Bacterial conjugation is the main mechanism for the wide spread dissemination of antibiotic resistance genes. Here, we found that conjugative traffic ATPases are the molecular target for the inhibition of conjugation by unsaturated fatty acids. Identification of this molecular target will provide us with a new tool for the rational design of more potent and efficient drugs to stop the transmission of antibiotic resistance genes.
DescriptionPMCID: PMC4908816
Publisher version (URL)https://doi.org/10.1111/mmi.13359
URIhttp://hdl.handle.net/10261/164249
Identifiersdoi: 10.1111/mmi.13359
e-issn: 1365-2958
issn: 0950-382X
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