4.6 Article

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

Journal

PLOS BIOLOGY
Volume 19, Issue 7, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.3001346

Keywords

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Funding

  1. National Institute of Allergy and Infectious Diseases [AI141883, AI148661, AI158080]
  2. Department of Veteran's Affairs [BX002788]
  3. Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Disease award

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Antibiotic resistance is a growing crisis in modern healthcare, traditionally thought to be caused by acquisition of genes or mutations, but heteroresistance may actually develop before resistance and often be a stage in its progression.
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.

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