Persistence against benzalkonium chloride promotes rapid evolution of tolerance during periodic disinfection

Nat Commun. 2021 Nov 23;12(1):6792. doi: 10.1038/s41467-021-27019-8.

Abstract

Biocides used as disinfectants are important to prevent the transmission of pathogens, especially during the current antibiotic resistance crisis. This crisis is exacerbated by phenotypically tolerant persister subpopulations that can survive transient antibiotic treatment and facilitate resistance evolution. Here, we show that E. coli displays persistence against a widely used disinfectant, benzalkonium chloride (BAC). Periodic, persister-mediated failure of disinfection rapidly selects for BAC tolerance, which is associated with reduced cell surface charge and mutations in the lpxM locus, encoding an enzyme for lipid A biosynthesis. Moreover, the fitness cost incurred by BAC tolerance turns into a fitness benefit in the presence of antibiotics, suggesting a selective advantage of BAC-tolerant mutants in antibiotic environments. Our findings highlight the links between persistence to disinfectants and resistance evolution to antimicrobials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Benzalkonium Compounds / pharmacology
  • Disinfectants / pharmacology*
  • Disinfection / methods
  • Drug Resistance, Bacterial / genetics*
  • Escherichia coli / drug effects*
  • Escherichia coli / genetics
  • Escherichia coli Proteins
  • Evolution, Molecular*
  • Genetic Loci
  • Microbial Sensitivity Tests

Substances

  • Anti-Bacterial Agents
  • Benzalkonium Compounds
  • Disinfectants
  • Escherichia coli Proteins
  • Acyltransferases
  • MsbB protein, E coli