title: Candida albicans VPS4 is required for secretion of aspartyl proteases and in vivo virulence.
abstract: Candida albicans secretes aspartyl proteases (Saps) during infection. Although Saps are secretory proteins, little is known about the intracellular trafficking and secretion of these proteins. We previously cloned and analyzed the C. albicans pre-vacuolar protein sorting gene VPS4, and demonstrated that extracellular Sap2p is absent in the culture supernatants of the vps4delta null mutant. We therefore investigated the role of the C. albicans pre-vacuolar secretion pathway in the trafficking of Sap4-6p and in vivo virulence. The C. albicans vps4delta mutant failed to produce extracellular Sap4-6p. Next, when tested in a mouse model of disseminated candidiasis, the vps4delta mutant was greatly attenuated in virulence. Histopathological analysis indicated that infection with the vps4delta mutant did not cause renal microabscess formation, in contrast to the wild-type strain. Our results imply that VPS4 is required for extracellular secretion of Sap4-6p, and that C. albicans requires an intact pre-vacuolar secretory pathway for wild-type virulence in vivo.
authors.affiliation: Division of Infectious Diseases, University of New Mexico Health Science Center, Albuquerque, NM 87108, USA. SamALee@salud.unm.edu
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Lee
authors.forename: Jason
authors.initials: J
authors.lastname: Jones
authors.forename: Sarah
authors.initials: S
authors.lastname: Hardison
authors.forename: John
authors.initials: J
authors.lastname: Kot
authors.forename: Zachary
authors.initials: Z
authors.lastname: Khalique
authors.forename: Stella M
authors.initials: SM
authors.lastname: Bernardo
authors.forename: Anna
authors.initials: A
authors.lastname: Lazzell
authors.forename: Carlos
authors.initials: C
authors.lastname: Monteagudo
authors.forename: Jose
authors.initials: J
authors.lastname: Lopez-Ribot
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002176:Candida albicans / Q000472:pathogenicity / Q000502:physiology*; D002177:Candidiasis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D056827:Endosomal Sorting Complexes Required for Transport; D005260:Female; D005656:Fungal Proteins / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D055571:Secretory Pathway; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins; D037521:Virulence Factors; D016282:Aspartic Acid Endopeptidases; C090753:SAP2 protein, Candida; C086392:SAP4 protein, Candida albicans; C090755:SAP5 protein, Candida albicans; C539750:VPS4 protein, Candida albicans