Bojang, Ebrima, Sheriff, Lozan, Morris, Emma, Rouvray, Sophie, Fu, Man Shun, Wellings, Chloe, Abdissa, Ketema, Stavrou, Victoria, Clark, Callum, Southam, Andrew D., and others. (2026) Vancomycin disrupts mitochondrial morphology and function and impairs macrophage fungal killing. mBio, . Article Number e00580-26. ISSN 2150-7511. (doi:10.1128/mbio.00580-26) (KAR id:114339)
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| Official URL: https://doi.org/10.1128/mbio.00580-26 |
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Abstract
Vancomycin is a widely prescribed antibiotic used in the treatment of gram-positive bacterial infections. We previously showed that this antibiotic disrupted protective antifungal immune responses via microbiome dysbiosis, enhancing susceptibility to invasive candidiasis. Antibiotics are an independent risk factor for developing this life-threatening fungal infection, but whether microbiota-independent mechanisms also drive this association is not clear. Here, we show that vancomycin directly impairs macrophage responses to Candida albicans, the main causative agent of invasive candidiasis. Vancomycin-treated macrophages were less able to kill C. albicans despite normal phagocytosis rates and were hyper-inflammatory and more likely to die during infection. Using a fluorescently labeled vancomycin, we observed vancomycin uptake by macrophages in vivo and within close proximity to the mitochondrial outer membrane. Vancomycin treatment led to a significant depolarization, reduced respiratory capacity, and a hyper-fragmented morphology of mitochondria, as well as increased cellular ROS production. Taken together, this work demonstrates direct effects of vancomycin on mammalian immune cells, helping us to understand the pro-inflammatory effects of this drug and how it promotes susceptibility to life-threatening fungal infection.
| Item Type: | Article |
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| DOI/Identification number: | 10.1128/mbio.00580-26 |
| Uncontrolled keywords: | Candida albicans, mitochondria, macrophages, hospital infections, postantibiotic effect, vancomycin, fungi |
| Subjects: | Q Science > QR Microbiology |
| Institutional Unit: | Schools > School of Natural Sciences > Biosciences |
| Former Institutional Unit: |
There are no former institutional units.
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| Funders: |
Wellcome Trust (https://ror.org/029chgv08)
Biotechnology and Biological Sciences Research Council (https://ror.org/00cwqg982) Diabetes UK (https://ror.org/050rgn017) British Infection Association (https://ror.org/02bvbqy06) Deutsche Forschungsgemeinschaft (https://ror.org/018mejw64) |
| Depositing User: | JISC Publications Router |
| Date Deposited: | 05 May 2026 08:15 UTC |
| Last Modified: | 07 May 2026 13:47 UTC |
| Resource URI: | https://kar.kent.ac.uk/id/eprint/114339 (The current URI for this page, for reference purposes) |
University of Kent Author Information
Hall, Rebecca A..
| Creator's ORCID: |
 https://orcid.org/0000-0002-4908-8168
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| CReDIT Contributor Roles: | Visualisation, Formal analysis, Funding acquisition, Supervision, Writing - original draft |
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