Overexpression of Candida albicans secreted aspartyl proteinase 2 or 5 is not sufficient for exacerbation of immunopathology in a murine model of vaginitis

Hubertine Willems, Winter S. Bruner, Katherine S. Barker, Junyan Liu, Glen Palmer, Brian Peters

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3 Citations (Scopus)

Abstract

The secreted aspartyl proteinases of Candida albicans have long been implicated in virulence at the mucosal surface, including contributions to colonization and immunopathogenesis during vulvovaginal candidiasis. In an effort to disentangle hypha-associated virulence factor regulation from morphological transition, the purpose of this study was to determine if overexpression of SAP2 or SAP5 in an efg1Δ/Δ cph1Δ/Δ mutant could restore the capacity to cause immunopathology during murine vaginitis to this avirulent hypofilamentous strain. Two similar yet distinct genetic approaches were used to construct expression vectors to achieve SAP overexpression, and both genetic and functional assays confirmed elevated SAP activity in transformed strains. Similar to previous findings, intravaginal challenge of C57BL/6 mice with hypha-defective strains attained high levels of mucosal colonization but failed to induce robust vaginal immunopathology (neutrophil recruitment, interleukin-1β [IL-1β] secretion, and lactate dehydrogenase release) compared to that with the hyphacompetent control. Moreover, constitutive expression of SAP2 or SAP5 in two distinct sets of such strains did not elicit immunopathological markers at levels above those observed during challenge with isogenic empty vector controls. Therefore, these results suggest that the physiological contributions of SAPs to vaginal immunopathology require hypha formation, other hypha-associated factors, or genetic interaction with EFG1 and/or CPH1 to cause symptomatic infection. Additionally, the outlined expression strategy and strain sets will be useful for decoupling other downstream morphogenetic factors from hyphal growth.

Original languageEnglish (US)
Article numbere00248-17
JournalInfection and Immunity
Volume85
Issue number10
DOIs
StatePublished - Jan 1 2017

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Vaginitis
Hyphae
Candida albicans
Vulvovaginal Candidiasis
Aspartic Acid Proteases
Neutrophil Infiltration
Virulence Factors
Interleukin-1
Inbred C57BL Mouse
L-Lactate Dehydrogenase
Virulence
Intercellular Signaling Peptides and Proteins
Candida SAP2 protein
Infection

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Overexpression of Candida albicans secreted aspartyl proteinase 2 or 5 is not sufficient for exacerbation of immunopathology in a murine model of vaginitis. / Willems, Hubertine; Bruner, Winter S.; Barker, Katherine S.; Liu, Junyan; Palmer, Glen; Peters, Brian.

In: Infection and Immunity, Vol. 85, No. 10, e00248-17, 01.01.2017.

Research output: Contribution to journalArticle

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