Priming with biocides: a pathway to antibiotic resistance?

Adkin, Pat; Hitchcock, Andrew; Smith, Laura J.; Walsh, Susannah E.

Abstract

Aims: To investigate the priming effects of sub-inhibitory concentrations of biocides on antibiotic resistance in bacteria. Methods and results: Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus were exposed to sub-inhibitory concentrations of biocides via a gradient plate method. Minimum inhibitory concentration (MIC) and antibiotic susceptibility were determined, and efflux pump inhibitors (thioridazine and chlorpromazine) were used to investigate antibiotic resistance mechanism(s). Escherichia coli displayed a 2-fold increase in MIC (32 to 64 mg l-1) to H2O2 which was stable after 15 passages, but lost after 6 weeks, and P. aeruginosa displayed a 2-fold increase in MIC (64 to 128 mg l-1) to BZK which was also stable for 15 passages. There were no other tolerances observed to biocides in E. coli, P. aeruginosa or S. aureus, however stable cross-resistance to antibiotics was observed in the absence of a stable increased tolerance to biocides. Six-fold increases in MIC to cephalothin and four-fold to ceftriaxone and ampicillin were observed in hydrogen peroxide primed E. coli. Chlorhexidine primed S. aureus showed a four-fold increase in MIC to oxacillin, and glutaraldehyde-primed P. aeruginosa showed four-fold (sulphatriad) and eight-fold (ciprofloxacin) increases in MIC. Thioridazine increased the susceptibility of E. coli to cephalothin and cefoxitin by four and two-fold respectively, and both thioridazine and chlorpromazine increased the susceptibility S. aureus to oxacillin by eight and four-fold respectively. Conclusions: These findings demonstrate that sub-inhibitory concentrations of biocides can prime bacteria to become resistant to antibiotics even in the absence of stable biocide tolerance and suggests activation of efflux mechanisms may be a contributory factor. Significance and impact of the study: This study demonstrates the effects of low-level exposure of biocides (priming) on antibiotic resistance even in the absence of obvious increased biocidal tolerance.

Citation

ADKIN, P., HITCHCOCK, A., SMITH, L.J. and WALSH, S.E. 2022. Priming with biocides: a pathway to antibiotic resistance? Journal of applied microbiology [online], 133(2), pages 830-841. Available from: https://doi.org/10.1111/jam.15564

• Journal Article Type: Article
• Acceptance Date: Mar 24, 2022
• Online Publication Date: Apr 5, 2022
• Publication Date: Aug 31, 2022
• Deposit Date: Apr 25, 2022
• Publicly Available Date: Apr 25, 2022
• Journal: Journal of Applied Microbiology
• Print ISSN: 1364-5072
• Electronic ISSN: 1365-2672
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 133
• Issue: 2
• Pages: 830-841
• DOI: https://doi.org/10.1111/jam.15564
• Keywords: Priming effects; Antiobiotic resistance; Bacteria; Sub-inhibitory concentrations
• Public URL: https://rgu-repository.worktribe.com/output/1635846