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Comment
. 2015 Mar 3;6(2):e00109.
doi: 10.1128/mBio.00109-15.

Finding the sweet spot: how human fungal pathogens acquire and turn the sugar inositol against their hosts

Chaoyang Xue  1
Affiliations
Comment

Finding the sweet spot: how human fungal pathogens acquire and turn the sugar inositol against their hosts

Chaoyang Xue. mBio. .

Abstract

Inositol is an essential nutrient with important structural and signaling functions in eukaryotes. Its role in microbial pathogenesis has been reported in fungi, protozoans, and eubacteria. In a recent article, Porollo et al. [mBio 5(6):e01834-14, 2014, doi:10.1128/mBio.01834-14] demonstrated the importance of inositol metabolism in the development and viability of Pneumocystis species--obligate fungal pathogens that remain unculturable in vitro. To understand their obligate nature, the authors used innovative comparative genomic approaches and discovered that Pneumocystis spp. are inositol auxotrophs due to the lack of inositol biosynthetic enzymes and that inositol insufficiency is a contributing factor preventing fungal growth in vitro. This work is in accord with other studies suggesting that inositol plays a conserved role in microbial pathogenesis. Inositol uptake and metabolism therefore may represent novel antimicrobial drug _targets. Using comparative genomics to analyze metabolic pathways offers a powerful tool to gain new insights into nutrient utilization in microbes, especially obligate pathogens.

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Figures

FIG 1
FIG 1
Inositol acquisition, metabolism, and control of cellular function. myo-inositol (referred as inositol) can be either imported from the environment via inositol transporters (ITRs) or synthesized intracellularly by converting glucose into inositol. Intracellular inositol is a precursor for producing phosphatidylinositol (PI), which can be utilized to produce additional inositol polyphosphates through PI kinase-mediated phosphorylation. Inositol intermediate metabolites and the enzymes (PI kinases and inositol polyphosphate phosphatases) that modulate their concentration direct diverse cellular processes, including calcium signaling, protein kinase C (PKC) signaling, osmotic stress, vesicle trafficking, nucleolar function, telomere length, chromatin remodeling, etc. The enzymes described in the article by Porollo et al. (3) are presented. Ino1 and Inm1 are two enzymes missing in Pneumocystis spp., while four enzymes (a to d) are enriched. (a) Inositol polyphosphate multikinase; (b) inositol pentakisphosphate 2-kinase; (c) phosphoinositide 5-phosphatase; (d) inositol-1,4-bisphosphate 1-phosphatase.
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