title: Transient and sustained bacterial adaptation following repeated sublethal exposure to microbicides and a novel human antimicrobial peptide.
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.
authors: Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom.
authors: Sarah
authors: S
authors: Forbes
authors: Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom.
authors: Curtis B
authors: CB
authors: Dobson
authors: Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom.
authors: Gavin J
authors: GJ
authors: Humphreys
authors: Manchester Pharmacy School, The University of Manchester, Manchester, United Kingdom andrew.mcbain@manchester.ac.uk.
authors: Andrew J
authors: AJ
authors: McBain
mesh_terms: D000222:Adaptation, Physiological; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001645:Biguanides / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects; D002710:Chlorhexidine / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D014260:Triclosan / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D001645:Biguanides; C031233:polihexanide; D014260:Triclosan; D002710:Chlorhexidine