Avirulence of Candida albicans auxotrophic mutants in a rat model of oropharyngeal candidiasis

Cole, Michael F.

doi:10.1016/0378-1097(95)00007-r

Cited by 17 publications

(27 citation statements)

References 3 publications

(6 reference statements)

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“…Our results demonstrate that hyphal induction by various environmental signals was not affected by inactivation of calcineurin. Deletion of CMP1 even resulted in an increased stimulation of hyphal (24), and since uridine auxotrophy renders C. albicans avirulent (4,21), this may affect virulence and virulence-related traits (1). Sundstrom and colleagues have recently shown that mutant phenotypes unrelated to inactivation of the target gene are obtained when the URA3 marker is inserted at a different genomic site or in a different way in the homozygous mutants than in the complemented strains (50).…”

Section: Discussionmentioning

confidence: 99%

Calcineurin Is Essential for Virulence in Candida albicans

Bader

Bodendorfer²,

Schröppel³

et al. 2003

Infect Immun

109

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Calcineurin is a conserved Ca2؉ -calmodulin-activated, serine/threonine-specific protein phosphatase that regulates a variety of physiological processes, e.g., cell cycle progression, polarized growth, and adaptation to salt and alkaline pH stresses. In the pathogenic yeast Cryptococcus neoformans, calcineurin is also essential for growth at 37°C and virulence. To investigate whether calcineurin plays a role in the virulence of Candida albicans, the major fungal pathogen of humans, we constructed C. albicans mutants in which both alleles of the CMP1 gene, encoding the calcineurin catalytic subunit, were deleted. The C. albicans ⌬cmp1 mutants displayed hypersensitivity to elevated Na ؉ , Li ؉ , and Mn 2؉ concentrations and to alkaline pH, phenotypes that have been described after calcineurin inactivation in the related yeast Saccharomyces cerevisiae. Unlike S. cerevisiae calcineurin mutants, which exhibit reduced susceptibility to high Ca 2؉ concentrations, growth of C. albicans was inhibited in the presence of 300 mM CaCl 2 after the deletion of CMP1, demonstrating that there are also differences in calcineurin-mediated cellular responses between these two yeast species. In contrast to C. neoformans, inactivation of calcineurin did not cause temperature sensitivity in C. albicans. In addition, hyphal growth, an important virulence attribute of C. albicans, was not impaired in the ⌬cmp1 mutants under a variety of inducing conditions. Nevertheless, the virulence of the mutants was strongly attenuated in a mouse model of systemic candidiasis, demonstrating that calcineurin signaling is essential for virulence in C. albicans.

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Section: Discussionmentioning

confidence: 99%

Calcineurin Is Essential for Virulence in Candida albicans

Bader

Bodendorfer²,

Schröppel³

et al. 2003

Infect Immun

109

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“…Vaginal mucosal mouse models, both in vivo (live mice inoculated with C. albicans on the vaginal mucosa) and ex vivo (vaginas excised from euthanized mice and then inoculated with C. albicans in tissue culture plates), show similar biofilm architectures, with clear yeast, hyphae, and extracellular matrix evident throughout the biofilms formed on top of the mucosal layers (72). Other animal models for monitoring biofilm formation include rodent oral mucosal, oropharyngeal, subcutaneous, and burn wound models (28, 44, 53, 166). Development of newer systems is under way to visualize the temporal and spatial progression of biofilm infections in live animals using bioluminescence imaging.…”

Section: In Vitro and In Vivo Development Of C Albicans Biofilmsmentioning

confidence: 99%

Candida albicans Biofilms and Human Disease

Nobile

Johnson

2015

Annu. Rev. Microbiol.

856

719

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In humans, microbial cells (including bacteria, archaea, and fungi) greatly outnumber host cells. Candida albicans is the most prevalent fungal species of the human microbiota; this species asymptomatically colonizes many areas of the body, particularly the gastrointestinal and genitourinary tracts of healthy individuals. Alterations in host immunity, stress, resident microbiota, and other factors can lead to C. albicans overgrowth, causing a wide range of infections, from superficial mucosal to hematogenously disseminated candidiasis. To date, most studies of C. albicans have been carried out in suspension cultures; however, the medical impact of C. albicans (like that of many other microorganisms) depends on its ability to thrive as a biofilm, a closely packed community of cells. Biofilms are notorious for forming on implanted medical devices, including catheters, pacemakers, dentures, and prosthetic joints, which provide a surface and sanctuary for biofilm growth. C. albicans biofilms are intrinsically resistant to conventional antifungal therapeutics, the host immune system, and other environmental perturbations, making biofilm-based infections a significant clinical challenge. Here, we review our current knowledge of biofilms formed by C. albicans and closely related fungal species.

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“…However, it has recently become evident that the use of the URA3 marker for the genetic engineering of C. albicans can cause problems in interpreting mutant phenotypes (Staab and Sundstrom, 2003). The expression level of an ectopically inserted URA3 gene depends on the integration locus (Lay et al, 1998), and since uridine auxotrophy renders C. albicans avirulent (Kirsch and Whitney, 1991;Cole et al, 1995), this may affect virulence and virulence related traits (Bain et al, 2001;Cheng et al, 2003). It has been shown that mutant phenotypes unrelated to inactivation of the target gene are obtained when the URA3 marker is inserted at a different genomic site or in a different way in the homozygous mutants as compared with the complemented strains (Sundstrom et al, 2002).…”

Section: Introductionmentioning

confidence: 98%