State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.
World J Microbiol Biotechnol. 2019 Jul 22;35(8):115. doi: 10.1007/s11274-019-2689-7.
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.
抗生素和砷（As）污染是全球公共卫生问题。先前，细菌 ABC 型外排蛋白 MacAB 据报道可赋予大环内酯类抗生素抗性，但不能赋予其他金属（类）抗性。在这项研究中，在对亚砷酸盐 [As(III)] 和几种抗生素具有抗性的根癌农杆菌 5A 中分析了 MacAB 对不同抗生素和几种金属（类）协同抗性的作用。macA 和 macB 基因共转录，并且在根癌农杆菌 5A 中缺失了 macB 并在大肠杆菌 AW3110 和大肠杆菌 S17-1 中异源表达。与野生型菌株 5A 相比，macB 缺失菌株降低了对几种大环内酯类和青霉素类抗生素的细菌抗性水平，但对头孢菌素类抗生素没有影响。此外，macB 缺失菌株对 As(III)的抗性降低，但对砷酸盐 [As(V)]、亚锑酸盐 [Sb(III)] 和氯化镉 [Cd(II)]的抗性没有降低。突变菌株 5A-ΔmacB 细胞比野生型细胞积累了更多的 As(III)。此外，MacAB 在大肠杆菌 S17-1 中的异源表达表明，MacAB 对大环内酯类、几种青霉素类抗生素和 As(III)的抗性是必需的，但对 As(V)没有影响。MacAB 在大肠杆菌 AW3110 中的异源表达降低了 As(III)的细胞积累，但没有降低 As(V)的细胞积累，表明 MacAB 负责将 As(III)排出细胞。这些结果表明，除了大环内酯类抗生素外，MacAB 还通过将它们从细胞中排出，赋予了对青霉素类抗生素和 As(III)的抗性。这一发现有助于更好地理解抗生素和金属（类）的细菌抗性机制。
