Bmh1p (14-3-3) mediates pathways associated with virulence in Candida albicans

Michelle N. Kelly, Douglas A. Johnston, Bethany A. Peel, Timothy W. Morgan, Glen Palmer, Joy E. Sturtevant

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The ability of the pathogenic fungus Candida albicans to cause disease requires rapid adaptation to changes in the host environment and to an evolving host immune response. The identification of 'virulence factors' using in vitro characterization of mutant strains has traditionally relied on a common set of phenotypic and biochemical assays (most often performed at 30 °C) and the subsequent correlation with their corresponding virulence in mouse models of disease. Utilizing a panel of isogenic mutants for the multifunctional signal-modulating 14-3-3 protein (Bmh1p), we have found that specific mutations affect a variety of different pathways currently associated with virulence, including those involved with the formation of filaments, as well as interaction with host immune cells. Surprisingly, our studies revealed that deficiencies in many of these pathways do not always correlate with virulence in a mouse model of disseminated infection. Mutations within the binding pocket of Bmh1p that affect the ability of the protein to efficiently bind ligand had varying effects on the results of a number of in vitro and in vivo assays. The capability, in vitro, to filament in embedment conditions, and to filament and form chlamydospores under microaerophilic conditions on cornmeal agar, does not correlate with virulence. It is likely that only a subset of hyphal signalling pathways is actually required for the establishment of infection in the disseminated mouse model. Most importantly, our results suggest that the delayed onset of lagphase growth in vitro at 37 °C, and not at 30 °C, results in an inability of these mutants to rapidly adjust to environmental changes in vivo and may be responsible for their increased clearance and reduced virulence. It is critical, therefore, that future in vitro studies of putative virulence factors in C. albicans include careful characterization at physiological temperatures.

Original languageEnglish (US)
Pages (from-to)1536-1546
Number of pages11
JournalMicrobiology
Volume155
Issue number5
DOIs
StatePublished - Aug 10 2009
Externally publishedYes

Fingerprint

Candida albicans
Virulence
Virulence Factors
14-3-3 Proteins
Mutation
Infection
Agar
Fungi
In Vitro Techniques
Ligands
Temperature
Growth
Proteins

All Science Journal Classification (ASJC) codes

  • Microbiology

Cite this

Kelly, M. N., Johnston, D. A., Peel, B. A., Morgan, T. W., Palmer, G., & Sturtevant, J. E. (2009). Bmh1p (14-3-3) mediates pathways associated with virulence in Candida albicans. Microbiology, 155(5), 1536-1546. https://doi.org/10.1099/mic.0.027532-0

Bmh1p (14-3-3) mediates pathways associated with virulence in Candida albicans. / Kelly, Michelle N.; Johnston, Douglas A.; Peel, Bethany A.; Morgan, Timothy W.; Palmer, Glen; Sturtevant, Joy E.

In: Microbiology, Vol. 155, No. 5, 10.08.2009, p. 1536-1546.

Research output: Contribution to journalArticle

Kelly, MN, Johnston, DA, Peel, BA, Morgan, TW, Palmer, G & Sturtevant, JE 2009, 'Bmh1p (14-3-3) mediates pathways associated with virulence in Candida albicans', Microbiology, vol. 155, no. 5, pp. 1536-1546. https://doi.org/10.1099/mic.0.027532-0
Kelly MN, Johnston DA, Peel BA, Morgan TW, Palmer G, Sturtevant JE. Bmh1p (14-3-3) mediates pathways associated with virulence in Candida albicans. Microbiology. 2009 Aug 10;155(5):1536-1546. https://doi.org/10.1099/mic.0.027532-0
Kelly, Michelle N. ; Johnston, Douglas A. ; Peel, Bethany A. ; Morgan, Timothy W. ; Palmer, Glen ; Sturtevant, Joy E. / Bmh1p (14-3-3) mediates pathways associated with virulence in Candida albicans. In: Microbiology. 2009 ; Vol. 155, No. 5. pp. 1536-1546.
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