Filamentation Is Associated with Reduced Pathogenicity of Multiple Non-<italic toggle="yes">albicans Candida</italic> Species

ABSTRACT Candidiasis affects a wide variety of immunocompromised and medically compromised patients. Candida albicans, a major human fungal pathogen, accounts for about 50% of all cases, while the remainder are caused by the less pathogenic non-albicans Candida species (NACS). These species are beli...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mohua Banerjee, Anna L. Lazzell, Jesus A. Romo, Jose L. Lopez-Ribot, David Kadosh
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	candidiasis infectious disease mycology morphology pathogenicity Candida species Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/aaef099d38464432ac75e3d1d02a62e5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:aaef099d38464432ac75e3d1d02a62e5
record_format	dspace
spelling	oai:doaj.org-article:aaef099d38464432ac75e3d1d02a62e52021-11-15T15:27:33ZFilamentation Is Associated with Reduced Pathogenicity of Multiple Non-<italic toggle="yes">albicans Candida</italic> Species10.1128/mSphere.00656-192379-5042https://doaj.org/article/aaef099d38464432ac75e3d1d02a62e52019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00656-19https://doaj.org/toc/2379-5042ABSTRACT Candidiasis affects a wide variety of immunocompromised and medically compromised patients. Candida albicans, a major human fungal pathogen, accounts for about 50% of all cases, while the remainder are caused by the less pathogenic non-albicans Candida species (NACS). These species are believed to be less pathogenic, in part, because they do not filament as readily or robustly as C. albicans, although definitive evidence is lacking. To address this question, we used strains for two NACS, Candida tropicalis and Candida parapsilosis, which were genetically engineered to constitutively express the key transcriptional regulator UME6 and drive strong filamentation both in vitro and during infection in vivo. Unexpectedly, both strains showed a dramatic reduction in organ fungal burden in response to UME6 expression. Consistent with these findings, we observed that a C. tropicalis hyperfilamentous mutant was significantly reduced and a filamentation-defective mutant was slightly increased for organ fungal burden. Comprehensive immune profiling generally did not reveal any significant changes in the host response to UME6 expression in the NACS that could explain the increased clearance of infection. Interestingly, whole-genome transcriptional profiling indicated that while genes important for filamentation were induced by UME6 expression in C. tropicalis and C. parapsilosis, other genes involved in a variety of processes important for pathogenesis were strongly downregulated. These findings suggest that there are fundamental evolutionary differences in the relationship between morphology and pathogenicity among Candida species and that NACS do not necessarily possess the same virulence properties as C. albicans. IMPORTANCE Many immunocompromised individuals, including HIV/AIDS and cancer patients, are susceptible to candidiasis. About half of all cases are caused by the major fungal pathogen Candida albicans, whereas the remainder are due to less pathogenic non-albicans Candida species (NACS). Generation of filamentous cells represents a major virulence property of C. albicans, and the NACS are believed to be less pathogenic, in part, because they do not filament as well as C. albicans does. To address this question, we determined the pathogenicity of two NACS strains that have been genetically engineered to promote filamentation during infection. Surprisingly, these strains showed a dramatic reduction in pathogenicity. The host immune response did not appear to be affected. However, unlike C. albicans, filamentation of the NACS was associated with downregulation of several genes important for pathogenicity processes. Our results suggest that there are fundamental evolutionary differences in the relationship between filamentation and pathogenesis in NACS compared to C. albicans.Mohua BanerjeeAnna L. LazzellJesus A. RomoJose L. Lopez-RibotDavid KadoshAmerican Society for Microbiologyarticlecandidiasisinfectious diseasemycologymorphologypathogenicityCandida speciesMicrobiologyQR1-502ENmSphere, Vol 4, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	candidiasis infectious disease mycology morphology pathogenicity Candida species Microbiology QR1-502
spellingShingle	candidiasis infectious disease mycology morphology pathogenicity Candida species Microbiology QR1-502 Mohua Banerjee Anna L. Lazzell Jesus A. Romo Jose L. Lopez-Ribot David Kadosh Filamentation Is Associated with Reduced Pathogenicity of Multiple Non-<italic toggle="yes">albicans Candida</italic> Species
description	ABSTRACT Candidiasis affects a wide variety of immunocompromised and medically compromised patients. Candida albicans, a major human fungal pathogen, accounts for about 50% of all cases, while the remainder are caused by the less pathogenic non-albicans Candida species (NACS). These species are believed to be less pathogenic, in part, because they do not filament as readily or robustly as C. albicans, although definitive evidence is lacking. To address this question, we used strains for two NACS, Candida tropicalis and Candida parapsilosis, which were genetically engineered to constitutively express the key transcriptional regulator UME6 and drive strong filamentation both in vitro and during infection in vivo. Unexpectedly, both strains showed a dramatic reduction in organ fungal burden in response to UME6 expression. Consistent with these findings, we observed that a C. tropicalis hyperfilamentous mutant was significantly reduced and a filamentation-defective mutant was slightly increased for organ fungal burden. Comprehensive immune profiling generally did not reveal any significant changes in the host response to UME6 expression in the NACS that could explain the increased clearance of infection. Interestingly, whole-genome transcriptional profiling indicated that while genes important for filamentation were induced by UME6 expression in C. tropicalis and C. parapsilosis, other genes involved in a variety of processes important for pathogenesis were strongly downregulated. These findings suggest that there are fundamental evolutionary differences in the relationship between morphology and pathogenicity among Candida species and that NACS do not necessarily possess the same virulence properties as C. albicans. IMPORTANCE Many immunocompromised individuals, including HIV/AIDS and cancer patients, are susceptible to candidiasis. About half of all cases are caused by the major fungal pathogen Candida albicans, whereas the remainder are due to less pathogenic non-albicans Candida species (NACS). Generation of filamentous cells represents a major virulence property of C. albicans, and the NACS are believed to be less pathogenic, in part, because they do not filament as well as C. albicans does. To address this question, we determined the pathogenicity of two NACS strains that have been genetically engineered to promote filamentation during infection. Surprisingly, these strains showed a dramatic reduction in pathogenicity. The host immune response did not appear to be affected. However, unlike C. albicans, filamentation of the NACS was associated with downregulation of several genes important for pathogenicity processes. Our results suggest that there are fundamental evolutionary differences in the relationship between filamentation and pathogenesis in NACS compared to C. albicans.
format	article
author	Mohua Banerjee Anna L. Lazzell Jesus A. Romo Jose L. Lopez-Ribot David Kadosh
author_facet	Mohua Banerjee Anna L. Lazzell Jesus A. Romo Jose L. Lopez-Ribot David Kadosh
author_sort	Mohua Banerjee
title	Filamentation Is Associated with Reduced Pathogenicity of Multiple Non-<italic toggle="yes">albicans Candida</italic> Species
title_short	Filamentation Is Associated with Reduced Pathogenicity of Multiple Non-<italic toggle="yes">albicans Candida</italic> Species
title_full	Filamentation Is Associated with Reduced Pathogenicity of Multiple Non-<italic toggle="yes">albicans Candida</italic> Species
title_fullStr	Filamentation Is Associated with Reduced Pathogenicity of Multiple Non-<italic toggle="yes">albicans Candida</italic> Species
title_full_unstemmed	Filamentation Is Associated with Reduced Pathogenicity of Multiple Non-<italic toggle="yes">albicans Candida</italic> Species
title_sort	filamentation is associated with reduced pathogenicity of multiple non-<italic toggle="yes">albicans candida</italic> species
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/aaef099d38464432ac75e3d1d02a62e5
work_keys_str_mv	AT mohuabanerjee filamentationisassociatedwithreducedpathogenicityofmultiplenonitalictoggleyesalbicanscandidaitalicspecies AT annallazzell filamentationisassociatedwithreducedpathogenicityofmultiplenonitalictoggleyesalbicanscandidaitalicspecies AT jesusaromo filamentationisassociatedwithreducedpathogenicityofmultiplenonitalictoggleyesalbicanscandidaitalicspecies AT josellopezribot filamentationisassociatedwithreducedpathogenicityofmultiplenonitalictoggleyesalbicanscandidaitalicspecies AT davidkadosh filamentationisassociatedwithreducedpathogenicityofmultiplenonitalictoggleyesalbicanscandidaitalicspecies
_version_	1718427970574483456

Filamentation Is Associated with Reduced Pathogenicity of Multiple Non-<italic toggle="yes">albicans Candida</italic> Species

Ejemplares similares