Department of Molecular Reproduction, Development, and Genetics, Indian Institute of Science, Bangalore, 560012, India.
Arch Microbiol. 2020 Aug;202(6):1301-1315. doi: 10.1007/s00203-020-01836-9. Epub 2020 Mar 4.
Antimicrobial resistance is a serious public health threat worldwide today. Escherichia coli is known to resist low doses of antibiotics in the presence of sodium salicylate and related compounds by mounting non-heritable transient phenotypic antibiotic resistance (PAR). In the present study, we demonstrate that Bgl bacterial strains harboring a functional copy of the β-glucoside (bgl) operon and are actively hydrolyzing plant-derived aromatic β-glucosides such as salicin show PAR to low doses of antibiotics. The aglycone released during metabolism of aromatic β-glucosides is responsible for conferring this phenotype by de-repressing the multiple antibiotics resistance (mar) operon. We also show that prolonged exposure of Bgl bacteria to aromatic β-glucosides in the presence of sub-lethal doses of antibiotics can lead to a significant increase in the frequency of mutants that show heritable resistance to higher doses of antibiotics. Although heritable drug resistance in many cases is known to reduce the fitness of the carrier strain, we did not see a cost associated with resistance in the mutants, most of which carry clinically relevant mutations. These findings indicate that the presence of the activated form of the bgl operon in the genome facilitates the survival of bacteria in environments in which both aromatic β-glucosides and antibiotics are present.
目前，抗生素耐药性是全世界面临的一个严重的公共卫生威胁。众所周知，大肠杆菌在水杨酸钠和相关化合物存在的情况下，能够通过产生非遗传性瞬时表型抗生素耐药性（PAR）来抵抗低剂量的抗生素。在本研究中，我们证明了携带功能性β-葡萄糖苷（bgl）操纵子的 Bgl 菌株，并且能够积极水解植物来源的芳香β-葡萄糖苷，如柳醇，表现出对低剂量抗生素的 PAR。在芳香β-葡萄糖苷代谢过程中释放的糖苷配基通过去阻遏多种抗生素耐药（mar）操纵子赋予了这种表型。我们还表明，Bgl 细菌在亚致死剂量抗生素存在下长时间接触芳香β-葡萄糖苷，可导致对更高剂量抗生素具有遗传性耐药性的突变体的频率显著增加。尽管众所周知，许多情况下遗传性药物耐药性会降低载体菌株的适应性，但我们没有看到突变体中存在与耐药性相关的成本，其中大多数携带临床相关的突变。这些发现表明，基因组中激活形式的 bgl 操纵子的存在促进了细菌在同时存在芳香β-葡萄糖苷和抗生素的环境中的生存。
