Cryptococcus and Beyond—Inositol Utilization and Its Implications for the Emergence of Fungal Virulence 英文参考文献.docVIP

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Cryptococcus and Beyond—Inositol Utilization and Its Implications for the Emergence of Fungal Virulence 英文参考文献.doc

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Cryptococcus and Beyond—Inositol Utilization and Its Implications for the Emergence of Fungal Virulence 英文参考文献

Pearls CryptococcusandBeyond—InositolUtilizationandIts ImplicationsfortheEmergenceofFungalVirulence ChaoyangXue1,2 * 1PublicHealthResearchInstitute,UniversityofMedicineandDentistryofNewJersey,Newark,NewJersey,UnitedStatesofAmerica,2DepartmentofMicrobiologyand MolecularGenetics,UniversityofMedicineandDentistryofNewJersey,Newark,NewJersey,UnitedStatesofAmerica Thereareoveronemillionfungalspeciesinnature,butonlya handfulofthemcausehumandiseases.Avarietyofdistinctfactors aid the virulence of fungi in their transition from environmental reservoirs to mammals. One important factor is their ability to acquirenutrientsefficientlysothattheycansurviveandthriveina nutrient-limiting host environment. The human fungal pathogen Cryptococcusneoformans(C.neoformans)isthemostcommoncauseof fungalmeningitis,yetthemechanismsofCryptococcusneurotropism remain poorly understood. Recent studies have revealed that Cryptococcushasevolvedsophisticatedacquisitionsystemstoutilize the carbohydrate inositol both in plant niches and in human brains,whereabundantinositolisavailable.Inositolutilizationin CryptococcusanditslikelycontributiontoCryptococcusvirulencemay represent one example of a common trait for the emergence of pathogensfromenvironmentalreservoirs. inositol in a multiple-step inositol biosynthetic pathway in which the inositol 3-phosphate synthase (Ino1) is the rate-determining enzyme[12].Inositolcanalsobeimportedfromtheextracellular environment via inositol transporters (ITRs). Cryptococcus can use inositol both as a carbon source and as a precursor to generate secondary messages that are important for regulating cellular functionsandforadaptingtoenvironmentalsignals.Interestingly, incontrasttoonlyoneortwoinositoltransporterspresentinmost fungi,Cryptococcus containsanunusually largeinositol transporter gene family with over ten members, derived in part from recent geneduplications,suggestingCryptococcus hasevolvedbyassociat- ing with the tree niches for inositol utilization [13]