Bacteria in nature often encounter non‐antibiotic antibacterials (NAAs), such as disinfectants and heavy metals, and they can evolve resistance via mechanisms that are also involved in antibiotic resistance. Understanding whether susceptibility to different types of antibacterials is non‐randomly associated across natural and clinical bacteria is therefore important for predicting the spread of resistance, yet there is no consensus about the extent of such associations or underlying mechanisms. We tested for associations between susceptibility phenotypes of 93 natural and clinical Escherichia coli isolates to various NAAs and antibiotics. Across all compound combinations, we detected a small number of non‐random associations, including a trio of positive associations among chloramphenicol, triclosan and benzalkonium chloride. We investigated genetic mechanisms that can explain such associations using genomic information, genetic knockouts and experimental evolution. This revealed some mutations that are selected for by experimental exposure to one compound and confer cross‐resistance to other compounds. Surprisingly, these interactions were asymmetric: selection for chloramphenicol resistance conferred cross‐resistance to triclosan and benzalkonium chloride, but selection for triclosan resistance did not confer cross‐resistance to other compounds. These results identify genetic changes involved in variable cross‐resistance across antibiotics and NAAs, potentially contributing to associations in natural and clinical bacteria.

中文翻译：

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天然、临床和实验室分离的大肠杆菌对抗生素、消毒剂和重金属的敏感性之间的关联。


自然界中的细菌经常遇到非抗生素抗菌剂（NAAs），例如消毒剂和重金属，它们可以通过也涉及抗生素耐药性的机制进化出耐药性。因此，了解自然和临床细菌对不同类型抗菌药物的敏感性是否非随机相关对于预测耐药性的传播非常重要，但对于这种关联的程度或潜在机制尚未达成共识。我们测试了 93 种天然和临床大肠杆菌分离株对各种 NAA 和抗生素的敏感性表型之间的关联。在所有化合物组合中，我们检测到少量非随机关联，包括氯霉素、三氯生和苯扎氯铵之间的三重正关联。我们利用基因组信息、基因敲除和实验进化研究了可以解释这种关联的遗传机制。这揭示了一些通过实验暴露于一种化合物而选择的突变，并赋予对其他化合物的交叉耐药性。令人惊讶的是，这些相互作用是不对称的：对氯霉素耐药性的选择赋予了对三氯生和苯扎氯铵的交叉耐药性，但对三氯生耐药性的选择并没有赋予对其他化合物的交叉耐药性。这些结果确定了与抗生素和 NAA 之间的可变交叉耐药性相关的遗传变化，可能有助于自然和临床细菌的关联。