Iron and fungal pathogenesis: a case study with Cryptococcus neoformans.
The acquisition of iron from mammalian hosts is an important aspect of infection because microbes must compete with the host for this nutrient and iron perception often regulates virulence factor expression. For example, iron levels are known to influence the elaboration of two major virulence factors, the polysaccharide capsule and melanin, in the pathogenic fungus Cryptococcus neoformans. This pathogen, which causes meningoencephalitis in immunocompromised people, acquires iron through the use of secreted reductants, cell surface reductases, a permease/ferroxidase uptake system and siderophore transporters. In addition, a master regulator, Cir1, integrates iron sensing with the expression of virulence factors, with growth at 37 degrees C and with signalling pathways that also influence virulence. The challenge ahead is to develop mechanistic views of the iron acquisition functions and regulatory schemes that operate when C. neoformans is in host tissue. Achieving these goals may contribute to an understanding of the notable predilection of the fungus for the mammalian central nervous system.
Jung
Won Hee
WH
The Michael Smith Laboratories, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
Kronstad
James W
JW
D000818:Animals; D002570:Ceruloplasmin / Q000378:metabolism / Q000502:physiology; D003300:Copper / Q000378:metabolism; D003453:Cryptococcosis / Q000378:metabolism / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006418:Heme / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism / Q000502:physiology; D051379:Mice; D010088:Oxidoreductases / Q000378:metabolism / Q000502:physiology; D017262:Siderophores / Q000378:metabolism / Q000502:physiology; D037521:Virulence Factors / Q000378:metabolism
D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D017262:Siderophores; D037521:Virulence Factors; D006418:Heme; D003300:Copper; D007501:Iron; D010088:Oxidoreductases; D002570:Ceruloplasmin