Candida albicans selection for human commensalism results in substantial within-host diversity without decreasing fitness for invasive disease
Open Access
- 19 May 2023
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Biology
- Vol. 21 (5), e3001822
- https://doi.org/10.1371/journal.pbio.3001822
Abstract
Candida albicans is a frequent colonizer of human mucosal surfaces as well as an opportunistic pathogen. C. albicans is remarkably versatile in its ability to colonize diverse host sites with differences in oxygen and nutrient availability, pH, immune responses, and resident microbes, among other cues. It is unclear how the genetic background of a commensal colonizing population can influence the shift to pathogenicity. Therefore, we examined 910 commensal isolates from 35 healthy donors to identify host niche-specific adaptations. We demonstrate that healthy people are reservoirs for genotypically and phenotypically diverse C. albicans strains. Using limited diversity exploitation, we identified a single nucleotide change in the uncharacterized ZMS1 transcription factor that was sufficient to drive hyper invasion into agar. We found that SC5314 was significantly different from the majority of both commensal and bloodstream isolates in its ability to induce host cell death. However, our commensal strains retained the capacity to cause disease in the Galleria model of systemic infection, including outcompeting the SC5314 reference strain during systemic competition assays. This study provides a global view of commensal strain variation and within-host strain diversity of C. albicans and suggests that selection for commensalism in humans does not result in a fitness cost for invasive disease.Funding Information
- University of Michigan (mCubed)
- University of Michigan (mCubed)
- National Institute of Allergy and Infectious Diseases (KAI137299)
- National Institute of Allergy and Infectious Diseases (AI007528)
- National Institute of General Medical Sciences (1F31HG010569)
- National Institute of General Medical Sciences (T32GM007544)
- University of Michigan (Postdoctoral Pioneer Program)
- CIFAR (Fungal Kingdom: Threats & Opportunities)
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