Transient and sustained bacterial adaptation following repeated sublethal exposure to microbicides and a novel human antimicrobial peptide

Antimicrob Agents Chemother. 2014 Oct;58(10):5809-17. doi: 10.1128/AAC.03364-14. Epub 2014 Jul 21.

Abstract

Microbicides (biocides) play an important role in the prevention and treatment of infections. While there is currently little evidence for in-use treatment failures attributable to acquired reductions in microbicide susceptibility, the susceptibility of some bacteria can be reduced by sublethal laboratory exposure to certain agents. In this investigation, a range of environmental bacterial isolates (11 genera, 18 species) were repeatedly exposed to four microbicides (cetrimide, chlorhexidine, polyhexamethylene biguanide [PHMB], and triclosan) and a cationic apolipoprotein E-derived antimicrobial peptide (apoEdpL-W) using a previously validated exposure system. Susceptibilities (MICs and minimum bactericidal concentrations [MBCs]) were determined before and after 10 passages (P10) in the presence of an antimicrobial and then after a further 10 passages without an antimicrobial to determine the stability of any adaptations. Bacteria exhibiting >4-fold increases in MBCs were further examined for alterations in biofilm-forming ability. Following microbicide exposure, ≥4-fold decreases in susceptibility (MIC or MBC) occurred for cetrimide (5/18 bacteria), apoEdpL-W (7/18), chlorhexidine (8/18), PHMB (8/18), and triclosan (11/18). Of the 34 ≥4-fold increases in the MICs, 15 were fully reversible, 13 were partially reversible, and 6 were nonreversible. Of the 26 ≥4-fold increases in the MBCs, 7 were fully reversible, 14 were partially reversible, and 5 were nonreversible. Significant decreases in biofilm formation in P10 strains occurred for apoEdpL-W (1/18 bacteria), chlorhexidine (1/18), and triclosan (2/18), while significant increases occurred for apoEdpL-W (1/18), triclosan (1/18), and chlorhexidine (2/18). These data indicate that the stability of induced changes in microbicide susceptibility varies but may be sustained for some combinations of a bacterium and a microbicide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Anti-Infective Agents / pharmacology*
  • Bacteria / drug effects*
  • Biguanides / pharmacology
  • Biofilms / drug effects
  • Chlorhexidine / pharmacology
  • Humans
  • Microbial Sensitivity Tests
  • Triclosan / pharmacology

Substances

  • Anti-Infective Agents
  • Biguanides
  • polihexanide
  • Triclosan
  • Chlorhexidine