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Strategies for acquiring the phospholipid metabolite inositol in pathogenic bacteria, fungi, and protozoa: making it and taking it

University of Tennessee, Knoxville

ABSTRACT

Myo-inositol (inositol) is an essential nutrient that is used for building phosphatidylinositol and its derivatives in eukaryotes and even in some eubacteria such as the mycobacteria. As a consequence, fungal, protozoan, and mycobacterial pathogens must be able to acquire inositol in order to proliferate and cause infection in their hosts. There are two primary mechanisms for acquiring inositol. One is to synthesize inositol from glucose-6-phosphate using two sequentially acting enzymes. The enzyme inositol-3-phosphate synthase (Ino1p) converts glucose-6-phosphate to inositol-3-phosphate, and then the inositol monophosphatase enzyme (IMPase) dephosphorylates inositol-3-phosphate to generate inositol. The other mechanism is to import inositol from the environment via inositol transporters. Inositol is readily abundant in the bloodstream of mammalian hosts providing a source from which many pathogens could potentially import inositol. However, despite this abundance of inositol in the host, some pathogens such as the bacterium Mycobacterium tuberculosis and the parasite Trypanosoma brucei must be able to make inositol de novo in order to cause disease (M. tuberculosis) or even grow (T. brucei). Other pathogens such as the fungus Candida albicans are equally adept at causing disease by importing inositol or by making it de novo. The role of inositol acquisition in the biology and pathogenesis of the parasite Leishmania and the fungus Cryptococcus are being explored as well. The specific strategies used by these pathogens to acquire inositol while in the host are discussed in relationship to each pathogen's unique metabolic requirements.

¹ E-mail: treynol6{at}utk.edu