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

PLoS Biol. 2021 Jul 20;19(7):e3001346. doi: 10.1371/journal.pbio.3001346. eCollection 2021 Jul.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Drug Resistance, Bacterial*
  • Enterobacteriaceae / drug effects
  • Microbial Sensitivity Tests
  • beta-Lactams / pharmacology*

Substances

  • Anti-Bacterial Agents
  • beta-Lactams