Dataset Information

Mp1p Is a Virulence Factor in Talaromyces (Penicillium) marneffei.

ABSTRACT:

Background

Talaromyces marneffei is an opportunistic dimorphic fungus prevalent in Southeast Asia. We previously demonstrated that Mp1p is an immunogenic surface and secretory mannoprotein of T. marneffei. Since Mp1p is a surface protein that can generate protective immunity, we hypothesized that Mp1p and/or its homologs are virulence factors.

Methodology/principal findings

We examined the pathogenic roles of Mp1p and its homologs in a mouse model. All mice died 21 and 30 days after challenge with wild-type T. marneffei PM1 and MP1 complemented mutant respectively. None of the mice died 60 days after challenge with MP1 knockout mutant (P<0.0001). Seventy percent of mice died 60 days after challenge with MP1 knockdown mutant (P<0.0001). All mice died after challenge with MPLP1 to MPLP13 knockdown mutants, suggesting that only Mp1p plays a significant role in virulence. The mean fungal loads of PM1 and MP1 complemented mutant in the liver, lung, kidney and spleen were significantly higher than those of the MP1 knockout mutant. Similarly, the mean load of PM1 in the liver, lung and spleen were significantly higher than that of the MP1 knockdown mutant. Histopathological studies showed an abundance of yeast in the kidney, spleen, liver and lung with more marked hepatic and splenic necrosis in mice challenged with PM1 compared to MP1 knockout and MP1 knockdown mutants. Likewise, a higher abundance of yeast was observed in the liver and spleen of mice challenged with MP1 complemented mutant compared to MP1 knockout mutant. PM1 and MP1 complemented mutant survived significantly better than MP1 knockout mutant in macrophages at 48 hours (P<0.01) post-infection. The mean fungal counts of Pichia pastoris GS115-MP1 in the liver (P<0.001) and spleen (P<0.05) of mice were significantly higher than those of GS115 at 24 hours post-challenge.

Conclusions/significance

Mp1p is a key virulence factor of T. marneffei. Mp1p mediates virulence by improving the survival of T. marneffei in macrophages.

SUBMITTER: Woo PC

PROVIDER: S-EPMC4999278 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Publications

Mp1p Is a Virulence Factor in Talaromyces (Penicillium) marneffei.

Woo Patrick C Y PC Lau Susanna K P SK Lau Candy C Y CC Tung Edward T K ET Chong Ken T K KT Yang Fengjuan F Zhang Hongmin H Lo Raymond K C RK Cai Jian-Pao JP Au-Yeung Rex K H RK Ng Wing-Fung WF Tse Herman H Wong Samson S Y SS Xu Simin S Lam Wai Hei WH Tse Man-Kit MK Sze Kong Hung KH Kao Richard Y RY Reiner Neil E NE Hao Quan Q Yuen Kwok-Yung KY

PLoS neglected tropical diseases 20160825 8

<h4>Background</h4>Talaromyces marneffei is an opportunistic dimorphic fungus prevalent in Southeast Asia. We previously demonstrated that Mp1p is an immunogenic surface and secretory mannoprotein of T. marneffei. Since Mp1p is a surface protein that can generate protective immunity, we hypothesized that Mp1p and/or its homologs are virulence factors.<h4>Methodology/principal findings</h4>We examined the pathogenic roles of Mp1p and its homologs in a mouse model. All mice died 21 and 30 days aft ...[more]

PMID: 27560160

Similar Datasets

Project description:Talaromyces marneffei is the most important thermal dimorphic fungus causing systemic mycosis in Southeast Asia. We report the discovery of a novel partitivirus, Talaromyces marneffeipartitivirus-1 (TmPV1). TmPV1 was detected in 7 (12.7%) of 55 clinical T. marneffei isolates. Complete genome sequencing of the seven TmPV1 isolates revealed two double-stranded RNA (dsRNA) segments encoding RNA-dependent RNA polymerase (RdRp) and capsid protein, respectively. Phylogenetic analysis showed that TmPV1 occupied a distinct clade among the members of the genus Gammapartitivirus Transmission electron microscopy confirmed the presence of isometric, nonenveloped viral particles of 30 to 45 nm in diameter, compatible with partitiviruses, in TmPV1-infected T. marneffei Quantitative reverse transcription-PCR (qRT-PCR) demonstrated higher viral load of TmPV1 in the yeast phase than in the mycelial phase of T. marneffei Two virus-free isolates, PM1 and PM41, were successfully infected by purified TmPV1 using protoplast transfection. Mice challenged with TmPV1-infected T. marneffei isolates showed significantly shortened survival time (P < 0.0001) and higher fungal burden in organs than mice challenged with isogenic TmPV1-free isolates. Transcriptomic analysis showed that TmPV1 causes aberrant expression of various genes in T. marneffei, with upregulation of potential virulence factors and suppression of RNA interference (RNAi)-related genes. This is the first report of a mycovirus in a thermally dimorphic fungus. Further studies are required to ascertain the mechanism whereby TmPV1 enhances the virulence of T. marneffei in mice and the potential role of RNAi-related genes in antiviral defense in T. marneffeiIMPORTANCETalaromyces marneffei (formerly Penicillium marneffei) is the most important thermal dimorphic fungus in Southeast Asia, causing highly fatal systemic penicilliosis in HIV-infected and immunocompromised patients. We discovered a novel mycovirus, TmPV1, in seven clinical isolates of T. marneffei TmPV1 belongs to the genus Gammapartitivirus of the family Partitiviridae We showed that TmPV1 enhanced the virulence of T. marneffei in mice, with shortened survival time and higher fungal burden in the organs of mice challenged with TmPV1-infected T. marneffei isolates than in those of mice challenged with virus-free isogenic isolates. Transcriptomics analysis showed that TmPV1 altered the expression of genes involved in various cellular processes in T. marneffei, with upregulation of potential virulence factors and suppression of RNAi machinery which may be involved in antiviral defense. This is the first report of a mycovirus in a thermal dimorphic fungus. The present results offer insights into mycovirus-fungus interactions and pathogenesis of thermal dimorphic fungi.

Dataset Information

Mp1p Is a Virulence Factor in Talaromyces (Penicillium) marneffei.

Background

Methodology/principal findings

Conclusions/significance

Publications

Mp1p Is a Virulence Factor in Talaromyces (Penicillium) marneffei.

Similar Datasets

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