Candida albicans ISW2 regulates chlamydospore suspensor cell formation and virulence In Vivo in a mouse model of disseminated candidiasis

Dhammika H.M.L.P. Navarathna, Ruvini U. Pathirana, Michail S. Lionakis, Kenneth Nickerson, David D. Roberts

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 Candidainfected 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.

Original languageEnglish (US)
Article numbere0164449
JournalPloS one
Volume11
Issue number10
DOIs
StatePublished - Oct 1 2016

Fingerprint

chlamydospores
candidiasis
Candida
Candidiasis
Candida albicans
Virulence
virulence
Physical properties
animal models
Centrifugation
Kidney
Virulence Factors
cells
Hyphae
kidneys
mice
Density Gradient Centrifugation
Spores
mutants
hyphae

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Candida albicans ISW2 regulates chlamydospore suspensor cell formation and virulence In Vivo in a mouse model of disseminated candidiasis. / Navarathna, Dhammika H.M.L.P.; Pathirana, Ruvini U.; Lionakis, Michail S.; Nickerson, Kenneth; Roberts, David D.

In: PloS one, Vol. 11, No. 10, e0164449, 01.10.2016.

Research output: Contribution to journalArticle

Navarathna, Dhammika H.M.L.P. ; Pathirana, Ruvini U. ; Lionakis, Michail S. ; Nickerson, Kenneth ; Roberts, David D. / Candida albicans ISW2 regulates chlamydospore suspensor cell formation and virulence In Vivo in a mouse model of disseminated candidiasis. In: PloS one. 2016 ; Vol. 11, No. 10.
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