title: Examination of the pathogenic potential of Candida albicans filamentous cells in an animal model of haematogenously disseminated candidiasis.
abstract: The opportunistic fungal pathogen Candida albicans is an increasingly common threat to human health. Candida albicans grows in several morphologies and mutant strains locked in yeast or filamentous forms have attenuated virulence in the murine model of disseminated candidiasis. Thus, the ability to change shape is important for virulence. The transcriptional repressors Nrg1p and Tup1p are required for normal regulation of C. albicans morphology. Strains lacking either NRG1 or TUP1 are constitutively pseudohyphal under yeast growth conditions, and display attenuated virulence in the disseminated model. To dissect the relative importance of hyphae and pseudohyphae during an infection, we used strains in which the morphological transition could be externally manipulated through controlled expression of NRG1 or TUP1. Remarkably, hyphal form inocula retain the capacity to cause disease. Whilst induction of a pseudohyphal morphology through depletion of TUP1 did result in attenuated virulence, this was not due to a defect in the ability to escape the bloodstream. Instead, we observed that pseudohyphal cells are cleared from tissues much more efficiently than either hyphal (virulent) or yeast form (avirulent) cells, indicating that different C. albicans morphologies have distinct interactions with host cells during an infection.
authors: Department of Biological Sciences, The University of Tennessee at Martin, Martin, TN 38238, USA.
authors: Ian A
authors: IA
authors: Cleary
authors: Department of Biology, and The South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX 78249, USA.
authors: Sara M
authors: SM
authors: Reinhard
authors: Department of Biology, and The South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX 78249, USA.
authors: Anna L
authors: AL
authors: Lazzell
authors: Departamento de Patologia, Facultad de Medicina y Odontologia, Universidad de Valencia, Avda. Blasco Ibañez, 17, 46010 Valencia, España.
authors: Carlos
authors: C
authors: Monteagudo
authors: Department of Biomedical Sciences, Grand Valley State University, 1 Campus Drive, Allendale, MI 49401, USA.
authors: Derek P
authors: DP
authors: Thomas
authors: Department of Biology, and The South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX 78249, USA.
authors: Jose L
authors: JL
authors: Lopez-Ribot
authors: Department of Biology, and The South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX 78249, USA stephen.saville@utsa.edu.
authors: Stephen P
authors: SP
authors: Saville
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000166:cytology / Q000254:growth & development / Q000472:pathogenicity*; D058387:Candidemia / Q000382:microbiology* / Q000473:pathology*; D004195:Disease Models, Animal; D025301:Hyphae / Q000254:growth & development / Q000472:pathogenicity; D051379:Mice; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014774:Virulence
chemical_list: D020890:Neuregulin-1; D012097:Repressor Proteins
keywords: Candida albicans; NRG1; TUP1; filamentation; pseudohyphae; virulence