Nonfilamentous C. albicans Mutants Are Avirulent

Abstract

Candida albicans and Saccharomyces cerevisiae switch from a yeast to a filamentous form. In Saccharomyces, this switch is controlled by two regulatory proteins, Ste12p and Phd1p. Single-mutant strains, ste12/ste12 or phd1/phd1, are partially defective, whereas the ste12/ste12 phd1/phd1 double mutant is completely defective in filamentous growth and is noninvasive. The equivalent cph1/cph1 efg1/efg1 double mutant in Candida (Cph1p is the Ste12p homolog and Efg1p is the Phd1p homolog) is also defective in filamentous growth, unable to form hyphae or pseudohyphae in response to many stimuli, including serum or macrophages. This Candida cph1/cph1 efg1/efg1 double mutant, locked in the yeast form, is avirulent in a mouse model.

(1‐aryloxy‐2‐hydroxypropyl)‐phenylpiperazine derivatives suppress Candida albicans virulence by interfering with morphological transition

“…Yeast‐to‐hyphae transition is essential and required for C. albicans to infect human mucosal tissue (Lo et al ., 1997; Saville et al ., 2003; Sudbery et al ., 2004; Finkel and Mitchell, 2011). The effects of piperazine derivatives on C. albicans morphological transition were then evaluated in vitro under hyphae induction conditions at 37°C.…”

“…C. albicans has a distinguishing feature, the yeast‐to‐hyphae dimorphism, which is the most important virulence factor that enables C. albicans to infect humans (Madhani and Fink, 1998; Brown and Gow, 1999; Staib et al ., 2000). During the initial stage of infection, C. albicans cells exhibit a planktonic yeast morphology that is avirulent, and a subsequent transition from yeast to hyphae leads to tissue invasion in patients (Sudbery et al ., 2004; Saville et al ., 2003; Lo et al ., 1997; Finkel and Mitchell, 2011). This ability to switch between yeast and hyphae is indispensable for the pathogenesis of C. albicans (Noble et al ., 2017).…”

Candida albicansdimorphism as a therapeutic target

“…The most convincing evidence of this is the fact that C. albicans mutants which are trapped either in the yeast (e.g., efg1D/cph1D, hgc1D) [29,30] or a filamentous form (e.g., nrg1D) [31] are attenuated in virulence.…”

The Flo8 Transcription Factor Is Essential for Hyphal Development and Virulence inCandida albicans

“…The ability to undergo reversible morphogenetic transitions between yeast, pseudohyphae, and hyphae has been shown to be important for its pathogenicity in systemic infections. Mutants defective in the morphogenetic transition show a much reduced virulence in mouse models of systemic infection (Lo et al, 1997;Whiteway and Oberholzer, 2004).…”