Filamentous growth and elevated vaginopathic potential of a nongerminative variant of Candida albicans expressing low virulence in systemic infection

Abstract

The vaginopathic potential and the intravaginal morphology of a nongerminative variant of Candida albicans, strain CA-2, were studied in a rat vaginitis model. Although it expressed low virulence in systemic infections, strain CA-2 was capable of causing a vaginal infection of the same duration and extent as that obtained in rats challenged with the germ-tube-forming strain C. albicans 3153 from the stock collection or with a fresh clinical isolate of C. albicans from a case of human vaginitis. During the experimental infection, the CA-2 cells did not maintain their yeast morphology but gave rise to single enlarged-elongated elements (1 to 2 days) which grew predominantly as coarse, short, pseudomycelium-like filaments (2 to 3 days) and then as long threads (7 days). These latter filaments were ultimately indistinguishable from the hyphal filaments formed by the germ-tube-forming strains, which, however, initially developed in the vagina by typical germ tube formation. This peculiar morphological development of strain CA-2 was not observed in organs of systemically infected mice, where, in contrast to strain 3153 which formed typical hyphae, strain CA-2 maintained a typical pattern of yeast growth. Vaginal isolates of strain CA-2 taken at different days of infection were found to be identical to the challenging CA-2 cells, in terms of biochemical characteristics, inability to form germ tubes in any medium at 37°C in vitro, echinocandin resistance, DNA biotype, and low virulence in systemic infections in mice. Thus, experimental vaginitis by strain CA-2 is associated with a peculiar filamentous growth in the vagina, through an apparently novel morphological development bypassing classical germ tube formation but ultimately leading to ordinary hyphae. The elevated vaginopathic potential of strain CA-2, in contrast to its low virulence in systemic infection, also suggests that different Candida virulence factors (and host responses) come into play in local and disseminated candidal infections.

The 65�kDa mannoprotein gene of Candida albicans encodes a putative ?-glucanase adhesin required for hyphal morphogenesis and experimental pathogenicity

“…In the self-healing mucosal model of infection (De Bernardis et al, 1993), the overall kinetics of fungus clearance from rat vagina was quite similar with all mutants and wild-type strain. However, the early rate of clearance (day 0-7 interval) was significantly (P < 0.05, Student's t-test, two-tailed) more accelerated when the challenger was the homozygous strain.…”

“…However, this null mutant was also significantly less pathogenic in a model of mucosal infection, an observation that has never been reported with other hyphae-defective mutants. The observation that CAMP65 gene plays also a role in mucosal virulence is relevant because the virulence traits which allow mucosal or deep-seated invasion may not be the same, and different are also the mechanisms of host response against the two infections (De Bernardis et al, 1993).…”

Rats clearing a vaginal infection by Candida albicans acquire specific, antibody-mediated resistance to vaginal reinfection

“…Vaginal fluid was taken from each animal every 2 days with a calibrated (1-l) plastic loop (Dispoinoc; PBI). The contents of each loop were vigorously suspended in 0.1 ml of PBS and aliquots were streaked over SDA plates containing 0.05% (wt/vol) chloramphenicol and incubated at 28ЊC for 48 to 72 h. One vaginal sample per rat per culture was evaluated, and the rat was considered infected when at least 1 CFU was present in one loop of vaginal fluid, i.e., a count of Ն10 3 CFU/ml (6,7). At intervals during the vaginal infection, the colonies developed on SDA were reidentified by standard diagnostic criteria (4,7).…”

“…Using oophorectomized, estrogen-treated rats, we obtained circumstantial evidence about the role of aspartyl-proteinase(s), a putative virulence factor of C. albicans in the pathogenesis of the vaginal infection (4,7). We have also recently demonstrated that the vaginal environment has unique, though still undefined, properties allowing for antigenic variations and hypha formation even by nongerminative mutants of C. albicans (6,9). Finally, we have shown that anti-idiotypic antibodies are elicited to a substantial level in the vaginas of rats immunized intravaginally or subcutaneously with an anti-yeast killer toxin monoclonal antibody.…”

Candida albicans growth and germ tube formation can be inhibited by simple diphenyl diselenides [(PhSe)2, (MeOPhSe)2, (p-Cl-PhSe)2, (F3CPhSe)2] and diphenyl ditelluride

“…[47][48][49][50] It has been shown in animal models of mucosal and systemic infections that the germ tube formation is an important feature in the virulence of C. albicans. 51,52 The compounds (PhSe) 2 and (MeOPhSe) 2 abolished the germ tube formation. These compounds are efficient in inhibiting both Candida growth and germ tube formation, which indicates their great potential as an antifungal agent.…”