David Perlin’s Lab at Hackensack Meridian Health Center for Discovery and Innovation, Nutley, NJ found that while drug-resistant C. glabrata isolates generally have lower fitness compared to susceptible isolates, they can persist in macrophage-rich organs like the spleen, which may help explain the high prevalence of drug resistance in the clinic.
- FLZR C. glabrata isolates are less fit inside macrophages than susceptible isolates, but this fitness cost can be reversed by acquiring ECR mutations.
- Macrophages infected with drug-resistant C. glabrata isolates mount an inflammatory response, while the drug-resistant cells downregulate processes required for in-host adaptation.
- Drug-resistant C. glabrata isolates are outcompeted by susceptible isolates in the gut and kidneys but show comparable fitness in the spleen.
Amir Arastehfar, Farnaz Daneshnia, Hrant Hovhannisyan, Nathaly Cabrera, Macit Ilkit, Jigar V Desai, Toni Gabaldón, Erika Shor, David S Perlin, A multidimensional assessment of in-host fitness costs of drug resistance in the opportunistic fungal pathogen Candida glabrata, FEMS Yeast Research, Volume 24, 2024, foae035, https://doi.org/10.1093/femsyr/foae035
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