title: Profiling of Candida albicans gene expression during intra-abdominal candidiasis identifies biologic processes involved in pathogenesis.
abstract: BACKGROUND
  The pathogenesis of intra-abdominal candidiasis is poorly understood.
  
  
  METHODS
  Mice were intraperitoneally infected with Candida albicans (1 × 10(6) colony-forming units) and sterile stool. nanoString assays were used to quantitate messenger RNA for 145 C. albicans genes within the peritoneal cavity at 48 hours.
  
  
  RESULTS
  Within 6 hours after infection, mice developed peritonitis, characterized by high yeast burdens, neutrophil influx, and a pH of 7.9 within peritoneal fluid. Organ invasion by hyphae and early abscess formation were evident 6 and 24 hours after infection, respectively; abscesses resolved by day 14. nanoString assays revealed adhesion and responses to alkaline pH, osmolarity, and stress as biologic processes activated in the peritoneal cavity. Disruption of the highly-expressed gene RIM101, which encodes an alkaline-regulated transcription factor, did not impact cellular morphology but reduced both C. albicans burden during early peritonitis and C. albicans persistence within abscesses. RIM101 influenced expression of 49 genes during intra-abdominal candidiasis, including previously unidentified Rim101 targets. Overexpression of the RIM101-dependent gene SAP5, which encodes a secreted protease, restored the ability of a rim101 mutant to persist within abscesses.
  
  
  CONCLUSIONS
  A mouse model of intra-abdominal candidiasis is valuable for studying pathogenesis and C. albicans gene expression. RIM101 contributes to persistence within intra-abdominal abscesses, at least in part through activation of SAP5.
authors.affiliation: Department of Medicine and.
authors.forename: Shaoji
authors.initials: S
authors.lastname: Cheng
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Clancy
authors.forename: Wenjie
authors.initials: W
authors.lastname: Xu
authors.forename: Frank
authors.initials: F
authors.lastname: Schneider
authors.forename: Binghua
authors.initials: B
authors.lastname: Hao
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Mitchell
authors.forename: M Hong
authors.initials: MH
authors.lastname: Nguyen
mesh_terms: D018784:Abdominal Abscess / Q000382:microbiology*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D002177:Candidiasis / Q000382:microbiology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D054884:Host-Pathogen Interactions; D051379:Mice; D010538:Peritonitis / Q000382:microbiology; D059467:Transcriptome; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D016282:Aspartic Acid Endopeptidases; C090755:SAP5 protein, Candida albicans
keywords: Candida albicans; RIM101; SAP5; in vivo gene expression; intra-abdominal candidiasis; nanoString