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Article

Insight into the AcrAB-TolC Complex Assembly Process Learned from Competition Studies

Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Isabelle Broutin, Attilio V. Vargiu, Henrietta Venter and Gilles Phan
Received: 12 May 2021 / Revised: 30 June 2021 / Accepted: 6 July 2021 / Published: 8 July 2021
The RND family efflux pump AcrAB-TolC in E. coli and its homologs in other Gram-negative bacteria are major players in conferring multidrug resistance to the cells. While the structure of the pump complex has been elucidated with ever-increasing resolution through crystallography and Cryo-EM efforts, the dynamic assembly process remains poorly understood. Here, we tested the effect of overexpressing functionally defective pump components in wild type E. coli cells to probe the pump assembly process. Incorporation of a defective component is expected to reduce the efflux efficiency of the complex, leading to the so called “dominant negative” effect. Being one of the most intensively studied bacterial multidrug efflux pumps, many AcrA and AcrB mutations have been reported that disrupt efflux through different mechanisms. We examined five groups of AcrB and AcrA mutants, defective in different aspects of assembly and substrate efflux. We found that none of them demonstrated the expected dominant negative effect, even when expressed at concentrations many folds higher than their genomic counterpart. The assembly of the AcrAB-TolC complex appears to have a proof-read mechanism that effectively eliminated the formation of futile pump complex. View Full-Text
Keywords: RND pump; dominant negative effect; assembly; protein-protein interaction; mutation RND pump; dominant negative effect; assembly; protein-protein interaction; mutation
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MDPI and ACS Style

Rajapaksha, P.; Ojo, I.; Yang, L.; Pandeya, A.; Abeywansha, T.; Wei, Y. Insight into the AcrAB-TolC Complex Assembly Process Learned from Competition Studies. Antibiotics 2021, 10, 830. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10070830

AMA Style

Rajapaksha P, Ojo I, Yang L, Pandeya A, Abeywansha T, Wei Y. Insight into the AcrAB-TolC Complex Assembly Process Learned from Competition Studies. Antibiotics. 2021; 10(7):830. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10070830

Chicago/Turabian Style

Rajapaksha, Prasangi, Isoiza Ojo, Ling Yang, Ankit Pandeya, Thilini Abeywansha, and Yinan Wei. 2021. "Insight into the AcrAB-TolC Complex Assembly Process Learned from Competition Studies" Antibiotics 10, no. 7: 830. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10070830

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