Genome restructuring and lineage diversification of Cryptococcus neoformans during chronic infection of human hosts

Summary: Opportunistic microbial pathogens that infect humans must adapt to radically different fitness landscapes as they transition from the external environment to the host niche. The nature, frequency, and magnitude of genomic changes that accompany adaptation to the human host niche are not wel...

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Main Authors: Marhiah C. Montoya, Kayla Wilhoit, Debra Murray, John R. Perfect, Paul M. Magwene
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725008745
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author Marhiah C. Montoya
Kayla Wilhoit
Debra Murray
John R. Perfect
Paul M. Magwene
author_facet Marhiah C. Montoya
Kayla Wilhoit
Debra Murray
John R. Perfect
Paul M. Magwene
author_sort Marhiah C. Montoya
collection DOAJ
description Summary: Opportunistic microbial pathogens that infect humans must adapt to radically different fitness landscapes as they transition from the external environment to the host niche. The nature, frequency, and magnitude of genomic changes that accompany adaptation to the human host niche are not well understood for many eukaryotic pathogens because of the logistical challenges of obtaining longitudinal samples of pathogen populations in individual patients. Drawing on a set of case studies, we characterize in-host genomic and phenotypic evolution of the opportunistic human fungal pathogen Cryptococcus neoformans during chronic infections. We find that fungal genome evolution during chronic infection is characterized by large-scale genome restructuring and increasing genomic heterogeneity within hosts. Phenotypic changes include diversification in virulence traits and antifungal susceptibility. Genotypically and phenotypically distinct sublineages arise and co-persist within the same host tissues, consistent with a model of strong and/or diversifying selection in the complex environment of human hosts.
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spelling doaj-art-5972d01c64e7403dad359702d36ffe7f2025-08-20T03:39:04ZengElsevierCell Reports2211-12472025-08-0144811610310.1016/j.celrep.2025.116103Genome restructuring and lineage diversification of Cryptococcus neoformans during chronic infection of human hostsMarhiah C. Montoya0Kayla Wilhoit1Debra Murray2John R. Perfect3Paul M. Magwene4Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USAUniversity Program in Genetics and Genomics, Duke University, Durham, NC, USADepartment of Biology, Duke University, Durham, NC, USADivision of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USADepartment of Biology, Duke University, Durham, NC, USA; Corresponding authorSummary: Opportunistic microbial pathogens that infect humans must adapt to radically different fitness landscapes as they transition from the external environment to the host niche. The nature, frequency, and magnitude of genomic changes that accompany adaptation to the human host niche are not well understood for many eukaryotic pathogens because of the logistical challenges of obtaining longitudinal samples of pathogen populations in individual patients. Drawing on a set of case studies, we characterize in-host genomic and phenotypic evolution of the opportunistic human fungal pathogen Cryptococcus neoformans during chronic infections. We find that fungal genome evolution during chronic infection is characterized by large-scale genome restructuring and increasing genomic heterogeneity within hosts. Phenotypic changes include diversification in virulence traits and antifungal susceptibility. Genotypically and phenotypically distinct sublineages arise and co-persist within the same host tissues, consistent with a model of strong and/or diversifying selection in the complex environment of human hosts.http://www.sciencedirect.com/science/article/pii/S2211124725008745CP: Microbiology
spellingShingle Marhiah C. Montoya
Kayla Wilhoit
Debra Murray
John R. Perfect
Paul M. Magwene
Genome restructuring and lineage diversification of Cryptococcus neoformans during chronic infection of human hosts
Cell Reports
CP: Microbiology
title Genome restructuring and lineage diversification of Cryptococcus neoformans during chronic infection of human hosts
title_full Genome restructuring and lineage diversification of Cryptococcus neoformans during chronic infection of human hosts
title_fullStr Genome restructuring and lineage diversification of Cryptococcus neoformans during chronic infection of human hosts
title_full_unstemmed Genome restructuring and lineage diversification of Cryptococcus neoformans during chronic infection of human hosts
title_short Genome restructuring and lineage diversification of Cryptococcus neoformans during chronic infection of human hosts
title_sort genome restructuring and lineage diversification of cryptococcus neoformans during chronic infection of human hosts
topic CP: Microbiology
url http://www.sciencedirect.com/science/article/pii/S2211124725008745
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