School of Natural Sciences, Massey University, Palmerston North, New Zealand.
Maurice Wilkins Centre, University of Auckland, Auckland, New Zealand.
Microbiology (Reading). 2022 Aug;168(8). doi: 10.1099/mic.0.001232.
Resistance to antimicrobials is normally caused by mutations in the drug targets or genes involved in antimicrobial activation or expulsion. Here we show that an strain, named DOC14, selected for increased resistance to the bile salt sodium deoxycholate, has no mutations in any ORF, but instead has a 2.1 Mb chromosomal inversion. The breakpoints of the inversion are two inverted copies of an IS element. Besides lowering deoxycholate susceptibility, the IS-mediated chromosomal inversion in the DOC14 mutant was found to increase bacterial survival upon exposure to ampicillin and vancomycin, and sensitize the cell to ciprofloxacin and meropenem, but does not affect bacterial growth or cell morphology in a rich medium in the absence of antibacterial molecules. Overall, our findings support the notion that a large chromosomal inversion can benefit bacterial cells under certain conditions, contributing to genetic variability available for selection during evolution. The DOC14 mutant paired with its isogenic parental strain form a useful model as bacterial ancestors in evolution experiments to study how a large chromosomal inversion influences the evolutionary trajectory in response to various environmental stressors.
抗生素耐药性通常是由药物靶点或参与抗生素激活或排出的基因中的突变引起的。在这里，我们表明，一株名为 DOC14 的 菌株，由于对胆汁盐脱氧胆酸钠的耐药性增加而被选择，其任何 ORF 均未发生突变，而是发生了 2.1 Mb 染色体倒位。该倒位的断点是 IS 元件的两个反向拷贝。除了降低脱氧胆酸盐的敏感性外，还发现 DOC14 突变体中 IS 介导的染色体倒位可增加细菌暴露于氨苄西林和万古霉素时的存活能力，并使细胞对环丙沙星和美罗培南敏感，但在没有抗菌分子的丰富培养基中不影响细菌生长或细胞形态。总的来说，我们的研究结果支持这样一种观点，即大的染色体倒位可以在某些条件下使细菌细胞受益，从而为进化过程中的选择提供可用的遗传变异性。DOC14 突变体与其同基因亲本菌株形成了一个有用的模型，作为细菌祖先在进化实验中，研究大的染色体倒位如何影响对各种环境胁迫的进化轨迹。
