In vitro long-term exposure to chlorhexidine or triclosan induces cross-resistance against azoles in Nakaseomyces glabratus

Abstract Background Topical antiseptics are crucial for preventing infections and reducing transmission of pathogens. However, commonly used antiseptic agents have been reported to cause cross-resistance to other antimicrobials in bacteria, which has not yet been described in yeasts. This study aims...

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Main Authors: Kathrin Spettel, Dominik Bumberger, Richard Kriz, Sarah Frank, Madita Loy, Sonia Galazka, Miranda Suchomel, Heimo Lagler, Athanasios Makristathis, Birgit Willinger
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Antimicrobial Resistance and Infection Control
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Online Access:https://doi.org/10.1186/s13756-024-01511-4
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author Kathrin Spettel
Dominik Bumberger
Richard Kriz
Sarah Frank
Madita Loy
Sonia Galazka
Miranda Suchomel
Heimo Lagler
Athanasios Makristathis
Birgit Willinger
author_facet Kathrin Spettel
Dominik Bumberger
Richard Kriz
Sarah Frank
Madita Loy
Sonia Galazka
Miranda Suchomel
Heimo Lagler
Athanasios Makristathis
Birgit Willinger
author_sort Kathrin Spettel
collection DOAJ
description Abstract Background Topical antiseptics are crucial for preventing infections and reducing transmission of pathogens. However, commonly used antiseptic agents have been reported to cause cross-resistance to other antimicrobials in bacteria, which has not yet been described in yeasts. This study aims to assess the in vitro efficacy of antiseptics against clinical and reference isolates of Candida albicans and Nakaseomyces glabratus, and whether prolonged exposure to antiseptics promotes the development of antifungal (cross)resistance. Methods A high-throughput approach for in vitro resistance development was established to simultaneously expose 96 C. albicans and N. glabratus isolates to increasing concentrations of a given antiseptic – chlorhexidine, triclosan or octenidine. Susceptibility testing and whole genome sequencing of yeast isolates pre- and post-exposure were performed. Results Long-term exposure to antiseptics does not result in the development of stable resistance to the antiseptics themselves. However, 50 N. glabratus isolates acquired resistance to azole antifungals after long-term exposure to triclosan or chlorhexidine, revealing newly acquired mutations in the PDR1 and PMA1 genes. Conclusions Chlorhexidine as well as triclosan, but not octenidine, were able to introduce selective pressure promoting resistance to azole antifungals. Although we assessed this phenomenon only in vitro, these findings warrant critical monitoring in clinical settings. Graphical Abstract
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spelling doaj-art-a7de9a9267264efeb68d2dffafb8904c2025-01-26T12:53:04ZengBMCAntimicrobial Resistance and Infection Control2047-29942025-01-0114111110.1186/s13756-024-01511-4In vitro long-term exposure to chlorhexidine or triclosan induces cross-resistance against azoles in Nakaseomyces glabratusKathrin Spettel0Dominik Bumberger1Richard Kriz2Sarah Frank3Madita Loy4Sonia Galazka5Miranda Suchomel6Heimo Lagler7Athanasios Makristathis8Birgit Willinger9Division of Clinical Microbiology, Department of Laboratory Medicine, Medical University of ViennaDivision of Clinical Microbiology, Department of Laboratory Medicine, Medical University of ViennaSection Biomedical Science, Health Sciences, FH Campus Wien University of Applied SciencesDivision of Clinical Microbiology, Department of Laboratory Medicine, Medical University of ViennaDivision of Clinical Microbiology, Department of Laboratory Medicine, Medical University of ViennaDivision of Data, Statistics and Risk Assessment, Austrian Agency for Health and Food Safety AGESInstitute for Hygiene and Applied Immunology, Medical University of ViennaDivision of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of ViennaDivision of Clinical Microbiology, Department of Laboratory Medicine, Medical University of ViennaDivision of Clinical Microbiology, Department of Laboratory Medicine, Medical University of ViennaAbstract Background Topical antiseptics are crucial for preventing infections and reducing transmission of pathogens. However, commonly used antiseptic agents have been reported to cause cross-resistance to other antimicrobials in bacteria, which has not yet been described in yeasts. This study aims to assess the in vitro efficacy of antiseptics against clinical and reference isolates of Candida albicans and Nakaseomyces glabratus, and whether prolonged exposure to antiseptics promotes the development of antifungal (cross)resistance. Methods A high-throughput approach for in vitro resistance development was established to simultaneously expose 96 C. albicans and N. glabratus isolates to increasing concentrations of a given antiseptic – chlorhexidine, triclosan or octenidine. Susceptibility testing and whole genome sequencing of yeast isolates pre- and post-exposure were performed. Results Long-term exposure to antiseptics does not result in the development of stable resistance to the antiseptics themselves. However, 50 N. glabratus isolates acquired resistance to azole antifungals after long-term exposure to triclosan or chlorhexidine, revealing newly acquired mutations in the PDR1 and PMA1 genes. Conclusions Chlorhexidine as well as triclosan, but not octenidine, were able to introduce selective pressure promoting resistance to azole antifungals. Although we assessed this phenomenon only in vitro, these findings warrant critical monitoring in clinical settings. Graphical Abstracthttps://doi.org/10.1186/s13756-024-01511-4NakaseomycesCandidaCross-resistanceAntisepticsChlorhexidineTriclosan
spellingShingle Kathrin Spettel
Dominik Bumberger
Richard Kriz
Sarah Frank
Madita Loy
Sonia Galazka
Miranda Suchomel
Heimo Lagler
Athanasios Makristathis
Birgit Willinger
In vitro long-term exposure to chlorhexidine or triclosan induces cross-resistance against azoles in Nakaseomyces glabratus
Antimicrobial Resistance and Infection Control
Nakaseomyces
Candida
Cross-resistance
Antiseptics
Chlorhexidine
Triclosan
title In vitro long-term exposure to chlorhexidine or triclosan induces cross-resistance against azoles in Nakaseomyces glabratus
title_full In vitro long-term exposure to chlorhexidine or triclosan induces cross-resistance against azoles in Nakaseomyces glabratus
title_fullStr In vitro long-term exposure to chlorhexidine or triclosan induces cross-resistance against azoles in Nakaseomyces glabratus
title_full_unstemmed In vitro long-term exposure to chlorhexidine or triclosan induces cross-resistance against azoles in Nakaseomyces glabratus
title_short In vitro long-term exposure to chlorhexidine or triclosan induces cross-resistance against azoles in Nakaseomyces glabratus
title_sort in vitro long term exposure to chlorhexidine or triclosan induces cross resistance against azoles in nakaseomyces glabratus
topic Nakaseomyces
Candida
Cross-resistance
Antiseptics
Chlorhexidine
Triclosan
url https://doi.org/10.1186/s13756-024-01511-4
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