Heteroresistance to beta-lactam antibiotics may often be a stage in the progression to antibiotic resistance

• Type of Material: Article
• Authors: Victor Band, Emory University; David Weiss, Emory University
• Language: English
• Date: 2021-07-01
• Publisher: PUBLIC LIBRARY SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © 2021 Band, Weiss
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pbio.3001346
• Title of Journal or Parent Work: PLOS BIOLOGY
• Volume: 19
• Issue: 7
• Start Page: e3001346
• End Page: e3001346
• Grant/Funding Information: This work was supported by National Institute of Allergy and Infectious Diseases grants [AI141883, AI148661, AI158080] to DSW and a Department of Veteran’s Affairs grant [BX002788] to DSW. DSW was also supported by a Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Disease award. The Multi-Site Gram-negative Surveillance Initiative from which clinical bacterial isolates were obtained is funded by the US Centers for Disease Control and Prevention. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Biology; Science & Technology; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

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.