Alternative oxidase mediates pathogen resistance in Paracoccidioides brasiliensis infection.

<h4>Background</h4>Paracoccidioides brasiliensis is a human thermal dimorphic pathogenic fungus. Survival of P. brasiliensis inside the host depends on the adaptation of this fungal pathogen to different conditions, namely oxidative stress imposed by immune cells.<h4>Aims and metho...

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Autores principales:	Orville Hernández Ruiz, Angel Gonzalez, Agostinho J Almeida, Diana Tamayo, Ana Maria Garcia, Angela Restrepo, Juan G McEwen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/b18ff481a4a04932ae6c77c5cb45a49c
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spelling	oai:doaj.org-article:b18ff481a4a04932ae6c77c5cb45a49c2021-11-18T09:14:44ZAlternative oxidase mediates pathogen resistance in Paracoccidioides brasiliensis infection.1935-27271935-273510.1371/journal.pntd.0001353https://doaj.org/article/b18ff481a4a04932ae6c77c5cb45a49c2011-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22039556/?tool=EBIhttps://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>Paracoccidioides brasiliensis is a human thermal dimorphic pathogenic fungus. Survival of P. brasiliensis inside the host depends on the adaptation of this fungal pathogen to different conditions, namely oxidative stress imposed by immune cells.<h4>Aims and methodology</h4>In this study, we evaluated the role of alternative oxidase (AOX), an enzyme involved in the intracellular redox balancing, during host-P. brasiliensis interaction. We generated a mitotically stable P. brasiliensis AOX (PbAOX) antisense RNA (aRNA) strain with a 70% reduction in gene expression. We evaluated the relevance of PbAOX during interaction of conidia and yeast cells with IFN-γ activated alveolar macrophages and in a mouse model of infection. Additionally, we determined the fungal cell's viability and PbAOX in the presence of H₂O₂.<h4>Results</h4>Interaction with IFN-γ activated alveolar macrophages induced higher levels of PbAOX gene expression in PbWt conidia than PbWt yeast cells. PbAOX-aRNA conidia and yeast cells had decreased viability after interaction with macrophages. Moreover, in a mouse model of infection, we showed that absence of wild-type levels of PbAOX in P. brasiliensis results in a reduced fungal burden in lungs at weeks 8 and 24 post-challenge and an increased survival rate. In the presence of H₂O₂, we observed that PbWt yeast cells increased PbAOX expression and presented a higher viability in comparison with PbAOX-aRNA yeast cells.<h4>Conclusions</h4>These data further support the hypothesis that PbAOX is important in the fungal defense against oxidative stress imposed by immune cells and is relevant in the virulence of P. brasiliensis.Orville Hernández RuizAngel GonzalezAgostinho J AlmeidaDiana TamayoAna Maria GarciaAngela RestrepoJuan G McEwenPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 5, Iss 10, p e1353 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Orville Hernández Ruiz Angel Gonzalez Agostinho J Almeida Diana Tamayo Ana Maria Garcia Angela Restrepo Juan G McEwen Alternative oxidase mediates pathogen resistance in Paracoccidioides brasiliensis infection.
description	<h4>Background</h4>Paracoccidioides brasiliensis is a human thermal dimorphic pathogenic fungus. Survival of P. brasiliensis inside the host depends on the adaptation of this fungal pathogen to different conditions, namely oxidative stress imposed by immune cells.<h4>Aims and methodology</h4>In this study, we evaluated the role of alternative oxidase (AOX), an enzyme involved in the intracellular redox balancing, during host-P. brasiliensis interaction. We generated a mitotically stable P. brasiliensis AOX (PbAOX) antisense RNA (aRNA) strain with a 70% reduction in gene expression. We evaluated the relevance of PbAOX during interaction of conidia and yeast cells with IFN-γ activated alveolar macrophages and in a mouse model of infection. Additionally, we determined the fungal cell's viability and PbAOX in the presence of H₂O₂.<h4>Results</h4>Interaction with IFN-γ activated alveolar macrophages induced higher levels of PbAOX gene expression in PbWt conidia than PbWt yeast cells. PbAOX-aRNA conidia and yeast cells had decreased viability after interaction with macrophages. Moreover, in a mouse model of infection, we showed that absence of wild-type levels of PbAOX in P. brasiliensis results in a reduced fungal burden in lungs at weeks 8 and 24 post-challenge and an increased survival rate. In the presence of H₂O₂, we observed that PbWt yeast cells increased PbAOX expression and presented a higher viability in comparison with PbAOX-aRNA yeast cells.<h4>Conclusions</h4>These data further support the hypothesis that PbAOX is important in the fungal defense against oxidative stress imposed by immune cells and is relevant in the virulence of P. brasiliensis.
format	article
author	Orville Hernández Ruiz Angel Gonzalez Agostinho J Almeida Diana Tamayo Ana Maria Garcia Angela Restrepo Juan G McEwen
author_facet	Orville Hernández Ruiz Angel Gonzalez Agostinho J Almeida Diana Tamayo Ana Maria Garcia Angela Restrepo Juan G McEwen
author_sort	Orville Hernández Ruiz
title	Alternative oxidase mediates pathogen resistance in Paracoccidioides brasiliensis infection.
title_short	Alternative oxidase mediates pathogen resistance in Paracoccidioides brasiliensis infection.
title_full	Alternative oxidase mediates pathogen resistance in Paracoccidioides brasiliensis infection.
title_fullStr	Alternative oxidase mediates pathogen resistance in Paracoccidioides brasiliensis infection.
title_full_unstemmed	Alternative oxidase mediates pathogen resistance in Paracoccidioides brasiliensis infection.
title_sort	alternative oxidase mediates pathogen resistance in paracoccidioides brasiliensis infection.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/b18ff481a4a04932ae6c77c5cb45a49c
work_keys_str_mv	AT orvillehernandezruiz alternativeoxidasemediatespathogenresistanceinparacoccidioidesbrasiliensisinfection AT angelgonzalez alternativeoxidasemediatespathogenresistanceinparacoccidioidesbrasiliensisinfection AT agostinhojalmeida alternativeoxidasemediatespathogenresistanceinparacoccidioidesbrasiliensisinfection AT dianatamayo alternativeoxidasemediatespathogenresistanceinparacoccidioidesbrasiliensisinfection AT anamariagarcia alternativeoxidasemediatespathogenresistanceinparacoccidioidesbrasiliensisinfection AT angelarestrepo alternativeoxidasemediatespathogenresistanceinparacoccidioidesbrasiliensisinfection AT juangmcewen alternativeoxidasemediatespathogenresistanceinparacoccidioidesbrasiliensisinfection
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Alternative oxidase mediates pathogen resistance in Paracoccidioides brasiliensis infection.

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