title: Spaceflight enhances cell aggregation and random budding in Candida albicans.
abstract: This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 452 genes compared to synchronous ground controls, which represented 8.3% of the analyzed ORFs. Spaceflight-cultured C. albicans-induced genes involved in cell aggregation (similar to flocculation), which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance. Finally, downregulation of genes involved in actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p.) infection model was observed under the conditions of this study. Collectively, our data represent an important basis for the assessment of the risk that commensal flora could play during human spaceflight missions. Furthermore, since the low fluid-shear environment of microgravity is relevant to physical forces encountered by pathogens during the infection process, insights gained from this study could identify novel infectious disease mechanisms, with downstream benefits for the general public.
authors: Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.
authors: Aurélie
authors: A
authors: Crabbé
authors: Sheila M
authors: SM
authors: Nielsen-Preiss
authors: Christine M
authors: CM
authors: Woolley
authors: Jennifer
authors: J
authors: Barrila
authors: Kent
authors: K
authors: Buchanan
authors: James
authors: J
authors: McCracken
authors: Diane O
authors: DO
authors: Inglis
authors: Stephen C
authors: SC
authors: Searles
authors: Mayra A
authors: MA
authors: Nelman-Gonzalez
authors: C Mark
authors: CM
authors: Ott
authors: James W
authors: JW
authors: Wilson
authors: Duane L
authors: DL
authors: Pierson
authors: Heidemarie M
authors: HM
authors: Stefanyshyn-Piper
authors: Linda E
authors: LE
authors: Hyman
authors: Cheryl A
authors: CA
authors: Nickerson
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D002177:Candidiasis / Q000382:microbiology / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D004875:Ergosterol / Q000096:biosynthesis / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D051379:Mice; D018384:Oxidative Stress / Q000235:genetics; D018085:Regulon; D013026:Space Flight; D013269:Stochastic Processes; D059467:Transcriptome; D014774:Virulence; D014893:Weightlessness
chemical_list: D018528:ATP-Binding Cassette Transporters; D050976:Basic-Leucine Zipper Transcription Factors; C426523:CAP1 protein, Candida albicans; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D004875:Ergosterol