Emory Antibiotic Resistance Center, Atlanta, Georgia, United States of America.
Department of Microbiology and Immunology, Emory University, Atlanta, Georgia, United States of America.
PLoS Biol. 2021 Jul 20;19(7):e3001346. doi: 10.1371/journal.pbio.3001346. eCollection 2021 Jul.
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.
抗生素耐药性是一个日益严重的危机，威胁着现代医疗保健的许多方面。传统观点认为，耐药性通常是由于获得耐药基因或突变引起的，而且当这种情况发生时，细菌种群中的所有细胞都表现出耐药性。相比之下，异质性耐药（HR）是一种抗生素耐药性形式，其中只有细菌种群中的一部分细胞对特定药物具有耐药性。这些耐药细胞在抗生素存在的情况下可以迅速复制，并导致治疗失败。HR 和耐药性之间的关系如何以及是否存在关系尚不清楚。我们使用耐碳青霉烯肠杆菌科（CRE）提供了证据，表明对β-内酰胺类药物的 HR 是在多年使用抗生素的过程中发展起来的，并且它逐渐被耐药性所取代。这表明 HR 可能经常在耐药性之前发展，并且经常是其进展的一个阶段，这可能代表我们对抗生素耐药性进化的理解发生了重大转变。
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