Role of an Expanded Inositol Transporter Repertoire in Cryptococcus neoformans Sexual Reproduction and Virulence

Xue, Chaoyang; Liu, Tongbao; Chen, Lydia; Li, Wenjun; Liu, Iris; Kronstad, James W.; Seyfang, Andreas; Heitman, Joseph

doi:10.1128/mbio.00084-10

Role of an Expanded Inositol Transporter Repertoire in Cryptococcus neoformans Sexual Reproduction and Virulence

Journal Article · Tue May 18 00:00:00 EDT 2010 · mBio (Online)

DOI:https://doi.org/10.1128/mbio.00084-10· OSTI ID:1626083

Xue, Chaoyang ^[1]; Liu, Tongbao ^[2]; Chen, Lydia ^[3]; Li, Wenjun ^[3]; Liu, Iris ^[4]; Kronstad, James W. ^[4]; Seyfang, Andreas ^[5]; Heitman, Joseph ^[3]

Duke Univ., Durham, NC (United States). Medical Center. Dept. of Molecular Genetics and Microbiology; Univ. of Medicine and Dentistry of New Jersey, Newark, NJ (United States). Public Health Research Inst.; DOE/OSTI
Univ. of Medicine and Dentistry of New Jersey, Newark, NJ (United States). Public Health Research Inst.
Duke Univ., Durham, NC (United States). Medical Center. Dept. of Molecular Genetics and Microbiology
Univ. of British Columbia, Vancouver, BC (Canada). Michael Smith Labs.
Univ. of South Florida, Tampa, FL (United States). Dept. of Molecular Medicine

Cryptococcus neoformans and Cryptococcus gattii are globally distributed human fungal pathogens and the leading causes of fungal meningitis. Recent studies reveal that myo-inositol is an important factor for fungal sexual reproduction. That C. neoformans can utilize myo-inositol as a sole carbon source and the existence of abundant inositol in the human central nervous system suggest that inositol is important for Cryptococcus development and virulence. In accord with this central importance of inositol, an expanded myo-inositol transporter (ITR) gene family has been identified in Cryptococcus. This gene family contains two phylogenetically distinct groups, with a total of 10 or more members in C. neoformans and at least six members in the sibling species C. gattii. These inositol transporter genes are differentially expressed under inositol-inducing conditions based on quantitative real-time PCR analyses. Expression of ITR genes in a Saccharomyces cerevisiae itr1 itr2 mutant lacking inositol transport can complement the slow-growth phenotype of this strain, confirming that ITR genes are bona fide inositol transporters. Gene mutagenesis studies reveal that the Itr1 and Itr1A transporters are important for myo-inositol stimulation of mating and that functional redundancies among the myo-inositol transporters likely exist. Deletion of the inositol 1-phosphate synthase gene INO1 in an itr1 or itr1a mutant background compromised virulence in a murine inhalation model, indicating the importance of inositol sensing and acquisition for fungal infectivity. Our study provides a platform for further understanding the roles of inositol in fungal physiology and virulence.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1626083

Journal Information:: mBio (Online), Journal Name: mBio (Online) Journal Issue: 1 Vol. 1; ISSN 2150-7511

Publisher:: American Society for Microbiology (ASM)Copyright Statement

Country of Publication:: United States

Language:: English

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