Low virulence of a morphological Candida albicans mutant

Diez-Orejas, Rosalı́a

doi:10.1016/s0378-1097(99)00250-5

Cited by 10 publications

(19 citation statements)

References 19 publications

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“…The extremely low virulence and the lack of tissue damage of this agerminative C. albicans mutant strain (92¢) in the murine systemic infection have been described Med Microbiol Immunol (2001) 189: 153±160 previously [13]. These features make this strain an excellent tool for the study of the defence mechanisms against its infection.…”

Section: Introductionmentioning

confidence: 91%

“…Host resistance to infection by C. albicans involves a number of speci®c and non-speci®c factors that have been most extensively explored in the mouse infection model [12,13,19,32]. This model closely reproduces, both in its nature and severity, the lesions seen in the human disease [38].…”

Section: Introductionmentioning

confidence: 99%

“…albicans is a dimorphic fungus, and its ability to modify its morphology from blastoconidia to hyphae is considered to be a virulence factor [13,18,24,27]. Blastoconidia and hyphae from C. albicans show different susceptibilities to phagocytic cells [3,6,11] probably due to their dierent sensitivities to macrophage products [1].…”

Section: Introductionmentioning

confidence: 99%

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Two different NO-dependent mechanisms account for the low virulence of a non-mycelial morphological mutant of Candida albicans

Diez-Orejas

Molero

Moro

et al. 2001

Medical Microbiology and Immunology

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We have previously described the low virulence of a Candida albicans morphological mutant: 92'. We have now used this strain to examine the role of phagocytes in its pathogenesis. Our results show that C. albicans 92' cannot evade innate host macrophage defence mechanisms as efficiently as the parental strain. In addition to the high susceptibility to phagocytosis by peritoneal macrophages, the NO produced by macrophages is a very important element in the low virulence of this agerminative mutant, a thesis supported by in vivo and in vitro experiments. Whereas the parental strain was able to inhibit macrophage NO production, the mutant was quite inefficient at reducing NO production by macrophages. In addition, the mutant showed high sensitivity to a NO generator. Treatment of mice with aminoguanidine (a preferred inducible NO synthase inhibitor) caused 90% mortality in 92' systemic infection, thus supporting a role for NO in the low virulence of this strain. Our data show that both the low inhibitory effect of 92' on macrophage NO production and the higher sensitivity to NO underlie the low virulence of this strain.

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Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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Two different NO-dependent mechanisms account for the low virulence of a non-mycelial morphological mutant of Candida albicans

Diez-Orejas

Molero

Moro

et al. 2001

Medical Microbiology and Immunology

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“…Several groups have reported that strains of C. albicans that cannot form hyphae are avirulent in mice (16,34,41,69). Thus, the characterization of the genes involved in dimorphism may lead to the discovery of new treatments for pathogenic fungi.…”

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confidence: 99%

Tagging Morphogenetic Genes by Insertional Mutagenesis in the Yeast Yarrowia lipolytica

et al. 2001

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The yeast Yarrowia lipolytica is distantly related to Saccharomyces cerevisiae, can be genetically modified, and can grow in both haploid and diploid states in either yeast, pseudomycelial, or mycelial forms, depending on environmental conditions. Previous results have indicated that the STE and RIM pathways, which mediate cellular switching in other dimorphic yeasts, are not required for Y. lipolytica morphogenesis. To identify the pathways involved in morphogenesis, we mutagenized a wild-type strain of Y. lipolytica with a Tn3 derivative. We isolated eight tagged mutants, entirely defective in hyphal formation, from a total of 40,000 mutants and identified seven genes homologous to S. cerevisiae CDC25, RAS2, BUD6, KEX2, GPI7, SNF5, and PPH21. We analyzed their abilities to invade agar and to form pseudomycelium or hyphae under inducing conditions and their sensitivity to temperature and to Calcofluor white. Chitin staining was used to detect defects in their cell walls. Our results indicate that a functional Ras-cyclic AMP pathway is required for the formation of hyphae in Y. lipolytica and that perturbations in the processing of extracellular, possibly parietal, proteins result in morphogenetic defects.

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“…It is thought that this ability is related to pathogenicity, which is reduced by the inhibition of hyphal growth, because morphological mutants defective in hyphal growth exhibit low virulence compared to the parental strain [2]. Understanding the dimorphism and screening for hyphal growth inhibitors should lead to the development of new antifungal therapies.…”

Section: Introductionmentioning

confidence: 99%

Relationship between Cell Morphology and Intracellular Potassium Concentration in Candida albicans

et al. 2006

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Previously we reported that valinomycin inhibited hyphal growth and induced growth as a chain of yeast cells under hyphal growth induction conditions in Candida albicans. To elucidate the hyphal growth inhibition by valinomycin, we examined the effect of various chemicals on the morphology and found that miconazole inhibited hyphal growth as well as valinomycin: both compounds promoted the leakage of potassium from cells. Analysis of intracellular potassium suggested that hyphal cells contain potassium at high concentrations in comparison with yeast cells. Hyphal growth inhibition by valinomycin was obstructed by the addition of serum. Potassium measurement showed that the addition of serum causes an increase in intracellular potassium, suggesting that the obstruction by serum might be due to an increase in intracellular potassium. The above-mentioned results strongly suggest that the addition of valinomycin and miconazole decreased interacellular potassium and this decrease inhibited hyphal transition.

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Low virulence of a morphological Candida albicans mutant

Cited by 10 publications

References 19 publications

Two different NO-dependent mechanisms account for the low virulence of a non-mycelial morphological mutant of Candida albicans

Two different NO-dependent mechanisms account for the low virulence of a non-mycelial morphological mutant of Candida albicans

Tagging Morphogenetic Genes by Insertional Mutagenesis in the Yeast Yarrowia lipolytica

Relationship between Cell Morphology and Intracellular Potassium Concentration in Candida albicans

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