Comparison of Phylogenetically Distinct <italic toggle="yes">Histoplasma</italic> Strains Reveals Evolutionarily Divergent Virulence Strategies

ABSTRACT Infection with the dimorphic fungus Histoplasma capsulatum results from the inhalation of contaminated soil. Disease outcome is variable and depends on the immune status of the host, number of organisms inhaled, and the H. capsulatum strain. H. capsulatum is divided into seven distinct clad...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Victoria E. Sepúlveda, Corinne L. Williams, William E. Goldman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f1acf659967741a5bc973a1423ceec06
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f1acf659967741a5bc973a1423ceec06
record_format	dspace
spelling	oai:doaj.org-article:f1acf659967741a5bc973a1423ceec062021-11-15T15:47:22ZComparison of Phylogenetically Distinct <italic toggle="yes">Histoplasma</italic> Strains Reveals Evolutionarily Divergent Virulence Strategies10.1128/mBio.01376-142150-7511https://doaj.org/article/f1acf659967741a5bc973a1423ceec062014-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01376-14https://doaj.org/toc/2150-7511ABSTRACT Infection with the dimorphic fungus Histoplasma capsulatum results from the inhalation of contaminated soil. Disease outcome is variable and depends on the immune status of the host, number of organisms inhaled, and the H. capsulatum strain. H. capsulatum is divided into seven distinct clades based on phylogenetic analyses, and strains from two separate clades have been identified in North America (denoted as NAm strains). We characterized an H. capsulatum isolate (WU24) from the NAm 1 lineage in relation to two other well-characterized Histoplasma isolates, the Panamanian strain G186A and the NAm 2 strain G217B. We determined that WU24 is a chemotype II strain and requires cell wall α-(1,3)-glucan for successful in vitro infection of macrophages. In a mouse model of histoplasmosis, WU24 exhibited a disease profile that was very similar to that of strain G186A at a high sublethal dose; however, at this dose G217B had markedly different kinetics. Surprisingly, infection with a lower dose mitigated many of the differences during the course of infection. The observed differences in fungal burden, disease kinetics, symptomology, and cytokine responses all indicate that there is a sophisticated relationship between host and fungus that drives the development and progression of histoplasmosis. IMPORTANCE Histoplasmosis has a wide range of clinical manifestations, presenting as mild respiratory distress, acute respiratory infection, or a life-threatening disseminated disease most often seen in immunocompromised patients. Additionally, the outcome appears to be dependent on the amount and strain of fungus inhaled. In this study, we characterized a recent clinical H. capsulatum isolate that was collected from an HIV+ individual in North America. In contrast to other isolates from the same lineage, this strain, WU24, infected both macrophages and wild-type mice. We determined that in contrast to many other North American strains, WU24 infection of macrophages is dependent on the presence of cell wall α-(1,3)-glucan. Surprisingly, comparison of WU24 with two previously characterized isolates revealed that many conclusions regarding relative strain virulence and certain hallmarks of histoplasmosis are dependent on the inoculum size.Victoria E. SepúlvedaCorinne L. WilliamsWilliam E. GoldmanAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 4 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Victoria E. Sepúlveda Corinne L. Williams William E. Goldman Comparison of Phylogenetically Distinct <italic toggle="yes">Histoplasma</italic> Strains Reveals Evolutionarily Divergent Virulence Strategies
description	ABSTRACT Infection with the dimorphic fungus Histoplasma capsulatum results from the inhalation of contaminated soil. Disease outcome is variable and depends on the immune status of the host, number of organisms inhaled, and the H. capsulatum strain. H. capsulatum is divided into seven distinct clades based on phylogenetic analyses, and strains from two separate clades have been identified in North America (denoted as NAm strains). We characterized an H. capsulatum isolate (WU24) from the NAm 1 lineage in relation to two other well-characterized Histoplasma isolates, the Panamanian strain G186A and the NAm 2 strain G217B. We determined that WU24 is a chemotype II strain and requires cell wall α-(1,3)-glucan for successful in vitro infection of macrophages. In a mouse model of histoplasmosis, WU24 exhibited a disease profile that was very similar to that of strain G186A at a high sublethal dose; however, at this dose G217B had markedly different kinetics. Surprisingly, infection with a lower dose mitigated many of the differences during the course of infection. The observed differences in fungal burden, disease kinetics, symptomology, and cytokine responses all indicate that there is a sophisticated relationship between host and fungus that drives the development and progression of histoplasmosis. IMPORTANCE Histoplasmosis has a wide range of clinical manifestations, presenting as mild respiratory distress, acute respiratory infection, or a life-threatening disseminated disease most often seen in immunocompromised patients. Additionally, the outcome appears to be dependent on the amount and strain of fungus inhaled. In this study, we characterized a recent clinical H. capsulatum isolate that was collected from an HIV+ individual in North America. In contrast to other isolates from the same lineage, this strain, WU24, infected both macrophages and wild-type mice. We determined that in contrast to many other North American strains, WU24 infection of macrophages is dependent on the presence of cell wall α-(1,3)-glucan. Surprisingly, comparison of WU24 with two previously characterized isolates revealed that many conclusions regarding relative strain virulence and certain hallmarks of histoplasmosis are dependent on the inoculum size.
format	article
author	Victoria E. Sepúlveda Corinne L. Williams William E. Goldman
author_facet	Victoria E. Sepúlveda Corinne L. Williams William E. Goldman
author_sort	Victoria E. Sepúlveda
title	Comparison of Phylogenetically Distinct <italic toggle="yes">Histoplasma</italic> Strains Reveals Evolutionarily Divergent Virulence Strategies
title_short	Comparison of Phylogenetically Distinct <italic toggle="yes">Histoplasma</italic> Strains Reveals Evolutionarily Divergent Virulence Strategies
title_full	Comparison of Phylogenetically Distinct <italic toggle="yes">Histoplasma</italic> Strains Reveals Evolutionarily Divergent Virulence Strategies
title_fullStr	Comparison of Phylogenetically Distinct <italic toggle="yes">Histoplasma</italic> Strains Reveals Evolutionarily Divergent Virulence Strategies
title_full_unstemmed	Comparison of Phylogenetically Distinct <italic toggle="yes">Histoplasma</italic> Strains Reveals Evolutionarily Divergent Virulence Strategies
title_sort	comparison of phylogenetically distinct <italic toggle="yes">histoplasma</italic> strains reveals evolutionarily divergent virulence strategies
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/f1acf659967741a5bc973a1423ceec06
work_keys_str_mv	AT victoriaesepulveda comparisonofphylogeneticallydistinctitalictoggleyeshistoplasmaitalicstrainsrevealsevolutionarilydivergentvirulencestrategies AT corinnelwilliams comparisonofphylogeneticallydistinctitalictoggleyeshistoplasmaitalicstrainsrevealsevolutionarilydivergentvirulencestrategies AT williamegoldman comparisonofphylogeneticallydistinctitalictoggleyeshistoplasmaitalicstrainsrevealsevolutionarilydivergentvirulencestrategies
_version_	1718427557899010048

Comparison of Phylogenetically Distinct <italic toggle="yes">Histoplasma</italic> Strains Reveals Evolutionarily Divergent Virulence Strategies

Ejemplares similares