Journal article
Discovery of CO2 tolerance genes associated with virulence in the fungal pathogen Cryptococcus neoformans
Nature microbiology, Vol.9(10), pp.2684-2695
10/2024
DOI: 10.1038/s41564-024-01792-w
PMCID: PMC12883045
PMID: 39232204
Abstract
Cryptococcus neoformans is a ubiquitous soil fungus and airborne pathogen that causes over 180,000 deaths each year. Cryptococcus must adapt to host CO2 levels to cause disease, but the genetic basis for this adaptation is unknown. We utilized quantitative trait loci mapping with 374 progeny from a cross between a CO2-tolerant clinical isolate and a CO2-sensitive environmental isolate to identify genetic regions regulating CO2 tolerance. To identify specific quantitative trait genes, we applied fine mapping through bulk segregant analysis of near-isogenic progeny with distinct tolerance levels to CO2. We found that virulence among near-isogenic strains in a murine model of cryptococcosis correlated with CO2 tolerance. Moreover, we discovered that sensitive strains may adapt in vivo to become more CO2 tolerant and more virulent. These findings highlight the underappreciated role of CO2 tolerance and its importance in the ability of an opportunistic environmental pathogen to cause disease.Cryptococcus neoformans is a ubiquitous soil fungus and airborne pathogen that causes over 180,000 deaths each year. Cryptococcus must adapt to host CO2 levels to cause disease, but the genetic basis for this adaptation is unknown. We utilized quantitative trait loci mapping with 374 progeny from a cross between a CO2-tolerant clinical isolate and a CO2-sensitive environmental isolate to identify genetic regions regulating CO2 tolerance. To identify specific quantitative trait genes, we applied fine mapping through bulk segregant analysis of near-isogenic progeny with distinct tolerance levels to CO2. We found that virulence among near-isogenic strains in a murine model of cryptococcosis correlated with CO2 tolerance. Moreover, we discovered that sensitive strains may adapt in vivo to become more CO2 tolerant and more virulent. These findings highlight the underappreciated role of CO2 tolerance and its importance in the ability of an opportunistic environmental pathogen to cause disease.
Details
- Title: Subtitle
- Discovery of CO2 tolerance genes associated with virulence in the fungal pathogen Cryptococcus neoformans
- Creators
- Benjamin J Chadwick - University of GeorgiaLaura C Ristow - University of IowaXiaofeng Xie - University of GeorgiaDamian J Krysan - University of IowaXiaorong Lin - University of Georgia
- Resource Type
- Journal article
- Publication Details
- Nature microbiology, Vol.9(10), pp.2684-2695
- DOI
- 10.1038/s41564-024-01792-w
- PMID
- 39232204
- PMCID
- PMC12883045
- NLM abbreviation
- Nat Microbiol
- ISSN
- 2058-5276
- eISSN
- 2058-5276
- Publisher
- NATURE PORTFOLIO
- Grant note
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID): R01AI147541
This work was supported by National Institutes of Health (http://www.niaid.nih.gov) (R01AI147541 to D.J.K. and X.L.) and University of Georgia Gene E. Michaels fund to X.L. The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication. We thank all Lin lab members and the UGA fungal group for their helpful suggestions, and to K. Devos and P. Qi for help with the genetic mapping.
- Language
- English
- Electronic publication date
- 09/04/2024
- Date published
- 10/2024
- Academic Unit
- Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
- Record Identifier
- 9984701659002771
Metrics
17 Record Views