2024-03-29T04:53:25Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1642492020-12-13T09:02:09Zcom_10261_3284com_10261_1col_10261_3285
Type IV traffic ATPase TrwD as molecular target to inhibit bacterial conjugation
Ripoll-Rozada, Jorge
García-Cazorla, Yolanda
Getino, María
Machón, Cristina
Machón, Cristina
Sanabria-Ríos, David J.
Cruz, Fernando de la
Cabezón, Elena
Arechaga, Ignacio
Ministerio de Economía y Competitividad (España)
National Center for Research Resources (US)
National Institute of General Medical Sciences (US)
National Institutes of Health (US)
Universidad Interamericana de Puerto Rico
European Commission
PMCID: PMC4908816
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. 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.
2018-04-26T12:58:54Z
2018-04-26T12:58:54Z
2016
2018-04-26T12:58:54Z
artículo
Molecular Microbiology 100(5): 912-921 (2016)
http://hdl.handle.net/10261/164249
10.1111/mmi.13359
http://dx.doi.org/10.13039/100000002
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/100000097
http://dx.doi.org/10.13039/100000057
26915347
eng
Postprint
https://doi.org/10.1111/mmi.13359
Sí
info:eu-repo/grantAgreement/EC/FP7/612146
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2014-55534-C2-1-P
info:eu-repo/grantAgreement/EC/FP7/282004
openAccess
Wiley-Blackwell