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ABSTRACT: Although several virulence factors and associated genes have been identified, the mechanisms that allow Cryptococcus neoformans to adapt during chronic infection and to persist in immunocompromised hosts remain poorly understood. Characterization of senescent cells of C. neoformans demonstrated that these cells exhibit a significantly enlarged cell body and capsule but still cross the blood-brain barrier. C. neoformans cells with advanced generational age are also more resistant to phagocytosis and killing by antifungals, which could promote their selection during chronic disease in humans. Senescent cells of RC-2, a C. neoformans strain that undergoes phenotypic switching, manifest switching rates up to 11-fold higher than those of younger cells. Infection experiments with labeled cells suggest that senescent yeast cells can potentially accumulate in vivo. Mathematical modeling incorporating different switching rates demonstrates how increased switching rates promote the emergence of hypervirulent mucoid variants during chronic infection. Our findings introduce the intriguing concept that senescence in eukaryotic pathogens could be a mechanism of microevolution that may promote pathoadaptation and facilitate evasion of an evolving immune response.
Eukaryotic Cell 06/2009; 8(6):858-66. · 3.60 Impact Factor
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ABSTRACT: Biofilm formation, an important virulence trait of Candida species was measured in 107 Candida isolates from 32 candidemic patients by XTT [2,3-bis (2-methoxy-4nitro-5-sulfo-phenyl)-2H-tetra-zolium-5-carboxanilide] activity and compared to biofilm formation of Candida isolates from oropharyngeal lesions of 19 AIDS patients. Biofilm formation by XTT varied among species and C. albicans; C. lusitaniae and C. krusei produced more biofilm than the other Candida species. C. tropicalis was the most dominant species isolated from blood followed by C. albicans, and other non-albicans species whereas only C. albicans was recovered from oral lesions. Importantly, though Biofilm formation was variable within a species it was stable in sequential isolates during chronic infection. Sequential isolates exhibited identical Karyotype pattern or RAPD patterns unless patients were co-infected with more than one strain. High biofilm formation was associated with slow growth rate but not with adherence. Murine infection studies demonstrated that, degree of in-vitro biofilm formation was associated with virulence in mice, as mice infected both with no and low biofilm formers survived longer than mice infected with high biofilm former C. albicans (p< or =0.001). We conclude that biofilm formation is a stable but strain specific characteristic that can greatly vary among C. albicans and non-albicans strains, and plays an important role in persistence of infection.
Microbes and Infection 05/2009; 11(8-9):753-61. · 3.10 Impact Factor
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ABSTRACT: Over the past three decades new fungal diseases have emerged that now constitute a major threat, especially for patients with chronic diseases and/or underlying immune defi ciencies. Despite the epidemiologic data, the emergence of stable drug-resistant or hyper-virulent fungal strains in human disease has not been demonstrated as seen in emerging viral and bacterial infections. Fungi are eukaryotic microbes that capitalize on a sophisticated built-in ability to generate phenotypic variability. This successful strategy allows them to undergo rapid adaptation in response to environmental challenges, such as individual body locations that may exhibit drastic differences in temperature and pH. Rapid microevolution can also confer drug resistance and protect them from the host's immune response. This review explores phenotypic switching in pathogenic fungi, including Candida spp and Cryptococcus spp, and how phenotypic switching contributes to the pathogenesis of fungal diseases.
Current Fungal Infection Reports 09/2008; 2(3):180-188.
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ABSTRACT: Vulvovaginal candidiasis is an important cause of morbidity in women of reproductive age. This study was carried out to determine the species prevalence and susceptibility pattern to fluconazole of yeasts isolated from the vagina of symptomatic women.
This prospective study was conducted in a rural primary health care center of north India from May 2003 to April 2004 and included 601 married, sexually active women (18-49 yr) with the self reported symptoms of vaginal discharge and/or genital itching and/or genital burning. Specific aetiology of the genitourinary symptoms including candidal infection were determined. Specimens from the lateral wall of vagina were subjected to direct wet mount microscopy and fungal culture on Sabouraud's dextrose agar. Susceptibility testing to fluconazole was carried out using broth microdilution method.
Yeasts were isolated in 111 (18.5%) women and these consisted of Candida glabrata (56, 50.4%), C. albicans (39, 35.1%), C. tropicalis (12, 10.8%), C. krusei (3, 2.7%) and C. parapsilosis (1, 0.9%). Susceptibility testing carried out on 30 representative isolates (15 C. glabrata, 10 C. albicans, 4 C. tropicalis and 1 C. parapsilosis) revealed that 21 isolates (70%) were susceptible (MIC, < or = 8 microg/ml) to fluconazole while 9 (30%) were susceptible-dose dependent (S-DD, MIC 16-32 microg/ml).
Our findings suggest a low prevalence of fluconazole resistance in vaginal candida isolates in our population. However, a high prevalence of non-albicans candida species and increased dose-dependent resistance in these isolates necessitates vigilance since this may warrant a change in the optimal therapy of non-albicans candida vaginitis.
The Indian journal of medical research 09/2007; 126(3):216-9. · 1.84 Impact Factor
