title: The role of Candida albicans SPT20 in filamentation, biofilm formation and pathogenesis.
abstract: Candida albicans is a ubiquitous fungus, which can cause very serious and sometimes life-threatening infections in susceptible patients. We used Caenorhabditis elegans as a model host to screen a library of C. albicans mutants for decreased virulence and identified SPT20 as important for virulence. The transcription co-activator SPT20 was identified originally as a suppressor of Ty and solo δ insertion mutations, which can cause transcription defects in Saccharomyces cerevisiae. It is resistant to the toxicity caused by overexpression of GAL4-VP16. We constructed a C. albicans spt20Δ/Δ mutant and found the spt20Δ/Δ strain was significantly less virulent than the wild-type strain SC5314 in C. elegans (p < 0.0001), Galleria mellonella (p < 0.01) and mice (p < 0.001). Morphologically, spt20Δ/Δ mutant cells demonstrated a "snow-flake" shape and clustered together; prolonged culture times resulted in increased size of the cluster. The clustered morphology was associated with defects in nuclei distribution, as the nuclei were not observed in many cellular compartments. In addition, the C. albicans spt20Δ/Δ mutant resulted in defects in hyphae and biofilm formation (compared to the wild-type strain, p < 0.05), and sensitivity to cell wall and osmotic stressors, and to antifungal agents. Thus our study demonstrated a role of C. albicans SPT20 in overall morphology and distribution of nuclear material, which may cause the defects in filamentation and biofilm formation directly when this gene is deleted.
authors.affiliation: Department of Respiration, Overseas Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, P. R. China; Department of Medicine, Infectious Diseases Division, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States of America; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Medicine, Infectious Diseases Division, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States of America; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Beth Burgwyn
authors.initials: BB
authors.lastname: Fuchs
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America; School of Pharmacy, Second Military Medical University, Shanghai, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Respiration, Overseas Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, P. R. China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Program in Immunology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Grace J
authors.initials: GJ
authors.lastname: Yuen
authors.affiliation: Phillips Academy, Andover, Massachusetts, United States of America.
authors.forename: Rosalyn B
authors.initials: RB
authors.lastname: Chen
authors.affiliation: Department of Medicine, Infectious Diseases Division, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States of America.
authors.forename: Elamparithi
authors.initials: E
authors.lastname: Jayamani
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Cleo
authors.initials: C
authors.lastname: Anastassopoulou
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Read
authors.initials: R
authors.lastname: Pukkila-Worley
authors.affiliation: Department of Medicine, Infectious Diseases Division, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States of America; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Coleman
authors.affiliation: Department of Medicine, Infectious Diseases Division, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States of America; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D001557:Benzenesulfonates / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D017173:Caenorhabditis elegans / Q000382:microbiology; D002176:Candida albicans / Q000166:cytology / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology*; D002177:Candidiasis / Q000382:microbiology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000378:metabolism*; D025301:Hyphae / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D009036:Moths / Q000382:microbiology; D009154:Mutation / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D014774:Virulence
chemical_list: D000935:Antifungal Agents; D001557:Benzenesulfonates; D005656:Fungal Proteins; C007061:C.I. Fluorescent Brightening Agent 28
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