In bacteria, evolution of resistance to one antibiotic is frequently associated with increased resistance (cross‐resistance) or increased susceptibility (collateral sensitivity) to other antibiotics. Cross‐resistance and collateral sensitivity are typically evaluated at the minimum inhibitory concentration (MIC). However, these susceptibility changes are not well characterized with respect to the mutant prevention concentration (MPC), the antibiotic concentration that prevents a single‐step mutation from occurring. We measured the MIC and the MPC for Staphylococcus epidermidis and 14 single‐drug resistant strains against seven antibiotics. We found that the MIC and the MPC were positively correlated but that this correlation weakened if cross‐resistance did not evolve. If any type of resistance did evolve, the range of concentrations between the MIC and the MPC tended to shift right and widen. Similar patterns of cross‐resistance and collateral sensitivity were observed at the MIC and MPC levels, though more symmetry was observed at the MIC level. Whole‐genome sequencing revealed mutations in both known‐target and nontarget genes. Moving forward, examining both the MIC and the MPC may lead to better predictions of evolutionary trajectories in antibiotic‐resistant bacteria.

中文翻译：

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使用突变体预防浓度和突变体选择窗口观察表皮葡萄球菌抗生素交叉耐药性和附带敏感性的演变


在细菌中，对一种抗生素的耐药性的进化通常与对其他抗生素的耐药性（交叉耐药性）增加或敏感性（附带敏感性）增加相关。交叉耐药性和附带敏感性通常在最低抑制浓度 (MIC) 下进行评估。然而，这些敏感性变化在突变预防浓度（MPC）（防止单步突变发生的抗生素浓度）方面并没有得到很好的表征。我们测量了表皮葡萄球菌和 14 种单一耐药菌株对 7 种抗生素的 MIC 和 MPC。我们发现 MIC 和 MPC 呈正相关，但如果交叉耐药性没有发展，这种相关性就会减弱。如果任何类型的耐药性确实出现，MIC 和 MPC 之间的浓度范围往往会向右移动并扩大。在 MIC 和 MPC 水平上观察到类似的交叉耐药性和附带敏感性模式，尽管在 MIC 水平上观察到更多的对称性。全基因组测序揭示了已知目标基因和非目标基因的突变。展望未来，检查 MIC 和 MPC 可能会更好地预测抗生素耐药细菌的进化轨迹。