Abstract
Formation of chlamydospores by Candida albicans was an established medical diagnostic test to confirm candidiasis before the molecular era. However, the functional role and pathological relevance of this in vitro morphological transition to pathogenesis in vivo remain unclear. We compared the physical properties of in vitro-induced chlamydospores with those of large C. albicans cells purified by density gradient centrifugation from Candida-infected mouse kidneys. The morphological and physical properties of these cells in kidneys of mice infected intravenously with wild type C. albicans confirmed that chlamydospores can form in infected kidneys. A previously reported chlamydospore-null Δisw2/Δisw2 mutant was used to investigate its role in virulence and chlamydospore induction. Virulence of the Δisw2/Δisw2 mutant strain was reduced 3.4-fold compared to wild type C. albicans or the ISW2 reconstituted strain. Altered host inflammatory reactions to the null mutant further indicate that ISW2 is a virulence factor in C. albicans. ISW2 deletion abolished chlamydospore formation within infected mouse kidneys, whereas the reconstituted strain restored chlamydospore formation in kidneys. Under chlamydospore inducing conditions in vitro, deletion of ISW2 significantly delayed chlamydospore formation, and those late induced chlamydospores lacked associated suspensor cells while attaching laterally to hyphae via novel spore-hypha septa. Our findings establish the induction of chlamydospores by C. albicans during mouse kidney colonization. Our results indicate that ISW2 is not strictly required for chlamydospores formation but is necessary for suspensor cell formation. The importance of ISW2 in chlamydospore morphogenesis and virulence may lead to additional insights into morphological differentiation and pathogenesis of C. albicans in the host microenvironment.
Highlights
Candida albicans is a commensal yeast fungus that is part of the human gastrointestinal and genitourinary tract microbiota
In vivo chlamydospore formation during C. albicans infections and their role in virulence have been poorly studied to date
We document the formation of chlamydospores in Candidainfected mouse kidneys and reduced virulence of a Δisw2/Δisw2 strain in a mouse model of disseminated candidiasis that coincides with an absence of chlamydospores in infected kidneys
Summary
Candida albicans is a commensal yeast fungus that is part of the human gastrointestinal and genitourinary tract microbiota. It has emerged as a significant opportunistic pathogen in the growing population of immunocompromised patients, where it causes considerable morbidity, mortality, and health care costs [1,2,3,4]. Disseminated candidiasis is highly prevalent among immunocompromised cancer patients undergoing chemotherapy [6, 7]. $1 billion is spent annually to manage disseminated candidiasis, which has ~40% mortality rate irrespective of treatment with currently available antifungal drugs [8]. C. albicans differentiates into mating competent opaque cells [10], regulated commensal state GUT (Gastrointestinally Induced Transition) cells [11], and thickwalled chlamydospores [12]
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