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Efflux proteins MacAB confer resistance to arsenite and penicillin/macrolide-type antibiotics in Agrobacterium tumefaciens 5A

Shi, Kaixiang, Cao, Min, Li, Chan, Huang, Jing, Zheng, Shixue, Wang, Gejiao
World journal of microbiology & biotechnology 2019 v.35 no.8 pp. 115
Agrobacterium radiobacter, Escherichia coli, antimony, arsenates, arsenic, arsenites, cadmium, cadmium chloride, genes, heterologous gene expression, macrolides, mutants, penicillins, proteins, public health, resistance mechanisms
Antibiotic and arsenic (As) contaminations are worldwide public health problems. Previously, the bacterial ABC-type efflux protein MacAB reportedly conferred resistance to macrolide-type antibiotics but not to other metal(loid)s. In this study, the roles of MacAB for the co-resistance of different antibiotics and several metal(loid)s were analyzed in Agrobacterium tumefaciens 5A, a strain resistant to arsenite [As(III)] and several types of antibiotics. The macA and macB genes were cotranscribed, and macB was deleted in A. tumefaciens 5A and heterologously expressed in Escherichia coli AW3110 and E. coli S17-1. Compared to the wild-type strain 5A, the macB deletion strain reduced bacterial resistance levels to several macrolide-type and penicillin-type antibiotics but not to cephalosporin-type antibiotics. In addition, the macB deletion strain showed lower resistance to As(III) but not to arsenate [As(V)], antimonite [Sb(III)] and cadmium chloride [Cd(II)]. The mutant strain 5A-ΔmacB cells accumulated more As(III) than the cells of the wild-type. Furthermore, heterologous expression of MacAB in E. coli S17-1 showed that MacAB was essential for resistance to macrolide, several penicillin-type antibiotics and As(III) but not to As(V). Heterologous expression of MacAB in E. coli AW3110 reduced the cellular accumulation of As(III) but not of As(V), indicating that MacAB is responsible for the efflux of As(III). These results demonstrated that, in addition to macrolide-type antibiotics, MacAB also conferred resistance to penicillin-type antibiotics and As(III) by extruding them out of cells. This finding contributes to a better understanding of the bacterial resistance mechanisms of antibiotics and metal(loid)s.