Antibiotic resistance is a growing crisis that threatens many aspects of modern healthcare. Dogma is that resistance often develops due to acquisition of a resistance gene or mutation and that when this occurs, all the cells in the bacterial population are phenotypically resistant. In contrast, heteroresistance (HR) is a form of antibiotic resistance where only a subset of cells within a bacterial population are resistant to a given drug. These resistant cells can rapidly replicate in the presence of the antibiotic and cause treatment failures. If and how HR and resistance are related is unclear. Using carbapenem-resistant Enterobacterales (CRE), we provide evidence that HR to beta-lactams develops over years of antibiotic usage and that it is gradually supplanted by resistance. This suggests the possibility that HR may often develop before resistance and frequently be a stage in its progression, potentially representing a major shift in our understanding of the evolution of antibiotic resistance.

中文翻译：

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对β-内酰胺类抗生素的异抗性通常可能是向抗生素抗性发展的一个阶段。

抗生素耐药性是一场日益严重的危机，威胁着现代医疗保健的许多方面。教条是耐药性通常是由于获得耐药基因或突变而产生的，当发生这种情况时，细菌种群中的所有细胞都具有表型耐药性。相比之下，异源抗性 (HR) 是一种抗生素抗性形式，其中细菌群体​​中只有一部分细胞对给定药物具有抗性。这些抗性细胞可以在抗生素存在的情况下快速复制并导致治疗失败。HR 和阻力是否以及如何相关尚不清楚。使用耐碳青霉烯肠杆菌 (CRE)，我们提供证据表明，β-内酰胺的 HR 会随着抗生素使用多年而发展，并且逐渐被耐药性所取代。