Discovery of CO 2 tolerance genes associated with virulence in the fungal pathogen Cryptococcus neoformans.

Autor: Chadwick BJ; Department of Plant Biology, University of Georgia, Athens, GA, USA., Ristow LC; Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA., Xie X; Department of Microbiology, University of Georgia, Athens, GA, USA., Krysan DJ; Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.; Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA., Lin X; Department of Plant Biology, University of Georgia, Athens, GA, USA. xiaorong.lin@uga.edu.; Department of Microbiology, University of Georgia, Athens, GA, USA. xiaorong.lin@uga.edu.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2024 Oct; Vol. 9 (10), pp. 2684-2695. Date of Electronic Publication: 2024 Sep 04.
DOI: 10.1038/s41564-024-01792-w
Abstrakt: Cryptococcus neoformans is a ubiquitous soil fungus and airborne pathogen that causes over 180,000 deaths each year. Cryptococcus must adapt to host CO 2 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 CO 2 -tolerant clinical isolate and a CO 2 -sensitive environmental isolate to identify genetic regions regulating CO 2 tolerance. To identify specific quantitative trait genes, we applied fine mapping through bulk segregant analysis of near-isogenic progeny with distinct tolerance levels to CO 2 . We found that virulence among near-isogenic strains in a murine model of cryptococcosis correlated with CO 2 tolerance. Moreover, we discovered that sensitive strains may adapt in vivo to become more CO 2 tolerant and more virulent. These findings highlight the underappreciated role of CO 2 tolerance and its importance in the ability of an opportunistic environmental pathogen to cause disease.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
Externí odkaz: