Sub-Inhibitory Concentrations of Chlorhexidine Induce Resistance to Chlorhexidine and Decrease Antibiotic Susceptibility in Neisseria gonorrhoeae

Objectives: Chlorhexidine digluconate (chlorhexidine) and Listerine® mouthwashes are being promoted as alternative treatment options to prevent the emergence of antimicrobial resistance in Neisseria gonorrhoeae. We performed in vitro challenge experiments to assess induction and evolution of resista...

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Autores principales:	Jolein G. E. Laumen, Christophe Van Dijck, Sheeba S. Manoharan-Basil, Saïd Abdellati, Irith De Baetselier, Vicky Cuylaerts, Tessa De Block, Dorien Van den Bossche, Basil B. Xavier, Surbhi Malhotra-Kumar, Chris Kenyon
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Neisseria gonnorhoeae antimicrobial resistance mouthwash Listerine® chlorhexidine cross-resistance Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c04cf7438d02453e9ad867af282a7303
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spelling	oai:doaj.org-article:c04cf7438d02453e9ad867af282a73032021-12-01T01:53:06ZSub-Inhibitory Concentrations of Chlorhexidine Induce Resistance to Chlorhexidine and Decrease Antibiotic Susceptibility in Neisseria gonorrhoeae1664-302X10.3389/fmicb.2021.776909https://doaj.org/article/c04cf7438d02453e9ad867af282a73032021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.776909/fullhttps://doaj.org/toc/1664-302XObjectives: Chlorhexidine digluconate (chlorhexidine) and Listerine® mouthwashes are being promoted as alternative treatment options to prevent the emergence of antimicrobial resistance in Neisseria gonorrhoeae. We performed in vitro challenge experiments to assess induction and evolution of resistance to these two mouthwashes and potential cross-resistance to other antimicrobials.Methods: A customized morbidostat was used to subject N. gonorrhoeae reference strain WHO-F to dynamically sustained Listerine® or chlorhexidine pressure for 18 days and 40 days, respectively. Cultures were sampled twice a week and minimal inhibitory concentrations (MICs) of Listerine®, chlorhexidine, ceftriaxone, ciprofloxacin, cefixime and azithromycin were determined using the agar dilution method. Isolates with an increased MIC for Listerine® or chlorhexidine were subjected to whole genome sequencing to track the evolution of resistance.Results: We were unable to increase MICs for Listerine®. Three out of five cultures developed a 10-fold increase in chlorhexidine MIC within 40 days compared to baseline (from 2 to 20 mg/L). Increases in chlorhexidine MIC were positively associated with increases in the MICs of azithromycin and ciprofloxacin. Low-to-higher-level chlorhexidine resistance (2–20 mg/L) was associated with mutations in NorM. Higher-level resistance (20 mg/L) was temporally associated with mutations upstream of the MtrCDE efflux pump repressor (mtrR) and the mlaA gene, part of the maintenance of lipid asymmetry (Mla) system.Conclusion: Exposure to sub-lethal chlorhexidine concentrations may not only enhance resistance to chlorhexidine itself but also cross-resistance to other antibiotics in N. gonorrhoeae. This raises concern regarding the widespread use of chlorhexidine as an oral antiseptic, for example in the field of dentistry.Jolein G. E. LaumenJolein G. E. LaumenChristophe Van DijckChristophe Van DijckSheeba S. Manoharan-BasilSaïd AbdellatiIrith De BaetselierVicky CuylaertsTessa De BlockDorien Van den BosscheBasil B. XavierSurbhi Malhotra-KumarChris KenyonChris KenyonFrontiers Media S.A.articleNeisseria gonnorhoeaeantimicrobial resistancemouthwashListerine®chlorhexidinecross-resistanceMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neisseria gonnorhoeae antimicrobial resistance mouthwash Listerine® chlorhexidine cross-resistance Microbiology QR1-502
spellingShingle	Neisseria gonnorhoeae antimicrobial resistance mouthwash Listerine® chlorhexidine cross-resistance Microbiology QR1-502 Jolein G. E. Laumen Jolein G. E. Laumen Christophe Van Dijck Christophe Van Dijck Sheeba S. Manoharan-Basil Saïd Abdellati Irith De Baetselier Vicky Cuylaerts Tessa De Block Dorien Van den Bossche Basil B. Xavier Surbhi Malhotra-Kumar Chris Kenyon Chris Kenyon Sub-Inhibitory Concentrations of Chlorhexidine Induce Resistance to Chlorhexidine and Decrease Antibiotic Susceptibility in Neisseria gonorrhoeae
description	Objectives: Chlorhexidine digluconate (chlorhexidine) and Listerine® mouthwashes are being promoted as alternative treatment options to prevent the emergence of antimicrobial resistance in Neisseria gonorrhoeae. We performed in vitro challenge experiments to assess induction and evolution of resistance to these two mouthwashes and potential cross-resistance to other antimicrobials.Methods: A customized morbidostat was used to subject N. gonorrhoeae reference strain WHO-F to dynamically sustained Listerine® or chlorhexidine pressure for 18 days and 40 days, respectively. Cultures were sampled twice a week and minimal inhibitory concentrations (MICs) of Listerine®, chlorhexidine, ceftriaxone, ciprofloxacin, cefixime and azithromycin were determined using the agar dilution method. Isolates with an increased MIC for Listerine® or chlorhexidine were subjected to whole genome sequencing to track the evolution of resistance.Results: We were unable to increase MICs for Listerine®. Three out of five cultures developed a 10-fold increase in chlorhexidine MIC within 40 days compared to baseline (from 2 to 20 mg/L). Increases in chlorhexidine MIC were positively associated with increases in the MICs of azithromycin and ciprofloxacin. Low-to-higher-level chlorhexidine resistance (2–20 mg/L) was associated with mutations in NorM. Higher-level resistance (20 mg/L) was temporally associated with mutations upstream of the MtrCDE efflux pump repressor (mtrR) and the mlaA gene, part of the maintenance of lipid asymmetry (Mla) system.Conclusion: Exposure to sub-lethal chlorhexidine concentrations may not only enhance resistance to chlorhexidine itself but also cross-resistance to other antibiotics in N. gonorrhoeae. This raises concern regarding the widespread use of chlorhexidine as an oral antiseptic, for example in the field of dentistry.
format	article
author	Jolein G. E. Laumen Jolein G. E. Laumen Christophe Van Dijck Christophe Van Dijck Sheeba S. Manoharan-Basil Saïd Abdellati Irith De Baetselier Vicky Cuylaerts Tessa De Block Dorien Van den Bossche Basil B. Xavier Surbhi Malhotra-Kumar Chris Kenyon Chris Kenyon
author_facet	Jolein G. E. Laumen Jolein G. E. Laumen Christophe Van Dijck Christophe Van Dijck Sheeba S. Manoharan-Basil Saïd Abdellati Irith De Baetselier Vicky Cuylaerts Tessa De Block Dorien Van den Bossche Basil B. Xavier Surbhi Malhotra-Kumar Chris Kenyon Chris Kenyon
author_sort	Jolein G. E. Laumen
title	Sub-Inhibitory Concentrations of Chlorhexidine Induce Resistance to Chlorhexidine and Decrease Antibiotic Susceptibility in Neisseria gonorrhoeae
title_short	Sub-Inhibitory Concentrations of Chlorhexidine Induce Resistance to Chlorhexidine and Decrease Antibiotic Susceptibility in Neisseria gonorrhoeae
title_full	Sub-Inhibitory Concentrations of Chlorhexidine Induce Resistance to Chlorhexidine and Decrease Antibiotic Susceptibility in Neisseria gonorrhoeae
title_fullStr	Sub-Inhibitory Concentrations of Chlorhexidine Induce Resistance to Chlorhexidine and Decrease Antibiotic Susceptibility in Neisseria gonorrhoeae
title_full_unstemmed	Sub-Inhibitory Concentrations of Chlorhexidine Induce Resistance to Chlorhexidine and Decrease Antibiotic Susceptibility in Neisseria gonorrhoeae
title_sort	sub-inhibitory concentrations of chlorhexidine induce resistance to chlorhexidine and decrease antibiotic susceptibility in neisseria gonorrhoeae
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/c04cf7438d02453e9ad867af282a7303
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Sub-Inhibitory Concentrations of Chlorhexidine Induce Resistance to Chlorhexidine and Decrease Antibiotic Susceptibility in Neisseria gonorrhoeae

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