title: Fungal heat-shock proteins in human disease.
abstract: Heat-shock proteins (hsps) have been identified as molecular chaperones conserved between microbes and man and grouped by their molecular mass and high degree of amino acid homology. This article reviews the major hsps of Saccharomyces cerevisiae, their interactions with trehalose, the effect of fermentation and the role of the heat-shock factor. Information derived from this model, as well as from Neurospora crassa and Achlya ambisexualis, helps in understanding the importance of hsps in the pathogenic fungi, Candida albicans, Cryptococcus neoformans, Aspergillus spp., Histoplasma capsulatum, Paracoccidioides brasiliensis, Trichophyton rubrum, Phycomyces blakesleeanus, Fusarium oxysporum, Coccidioides immitis and Pneumocystis jiroveci. This has been matched with proteomic and genomic information examining hsp expression in response to noxious stimuli. Fungal hsp90 has been identified as a target for immunotherapy by a genetically recombinant antibody. The concept of combining this antibody fragment with an antifungal drug for treating life-threatening fungal infection and the potential interactions with human and microbial hsp90 and nitric oxide is discussed.
authors.affiliation: Department of Medical Microbiology, Clinical Sciences Building, University of Manchester, Manchester Royal Infirmary, Manchester, UK. james.burnie@cmmc.nhs.uk
authors.forename: James P
authors.initials: JP
authors.lastname: Burnie
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Carter
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Hodgetts
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Matthews
mesh_terms: D005656:Fungal Proteins / Q000378:metabolism; D005658:Fungi / Q000378:metabolism* / Q000472:pathogenicity*; D015966:Gene Expression Regulation, Fungal; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D009181:Mycoses / Q000382:microbiology* / Q000628:therapy
chemical_list: D005656:Fungal Proteins; D006360:Heat-Shock Proteins