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ABSTRACT: Candida parapsilosis species complex includes three closely related species, namely C. parapsilosis (sensu stricto), C. orthopsilosis, and C. metapsilosis. Unlike most other yeast lineages, members of this species complex possess a linear mitochondrial genome. Yet, its circularized mutant form was identified in strains of C. orthopsilosis and C. metapsilosis. To investigate the underlying variability, we performed comparative analyses of the complete mitochondrial DNA sequences in a collection of strains. Our results demonstrate that in contrast to C. parapsilosis and C. metapsilosis, C. orthopsilosis exhibits remarkably high nucleotide diversity whose pattern is consistent with intraspecific genetic exchange.
Mitochondrion 07/2012; 12(5):514-9. · 3.62 Impact Factor
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ABSTRACT: The host factors that contribute to the increased susceptibility of preterm neonates to invasive candidiasis have not been fully identified. In addition, there has been a lack of suitable models to study this problem. We show that rat pups, similar to premature neonates, display increased susceptibility to experimental Candida albicans infection. Further, we find that both C. albicans and Candida parapsilosis lipase disruptant mutants exhibit decreased virulence in rat pups, demonstrating the utility of the model to evaluate the impact of specific genes in disease pathogenesis. Our findings highlight the contribution of lipases to the virulence of C. albicans and C. parapsilosis and provide a new system to study the increased susceptibility of neonates to Candida infections.
Mycopathologia 06/2011; 172(3):169-78. · 1.65 Impact Factor
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ABSTRACT: Neutral lipid storage in lipid droplets (LDs) is a conserved process across diverse species. Although significant attention has focused on LDs in the biology of obesity, diabetes, and atherosclerosis, there is limited information on the role of LDs in pathogenic fungi. We have disrupted the Fat storage-Inducing Transmembrane (FIT) protein 2 genes of the emerging pathogenic fungus Candida parapsilosis and demonstrated that LD formation is significantly reduced in the mutant cells. Disruption of FIT2 genes also reduced accumulation of triacylglycerols. The production of other lipids such as phospholipids and steryl esters were also affected in the mutant strain. Inhibition of de novo fatty acid biosynthesis by triclosan in the FIT2 disruptants reduced fungal growth in rich medium YPD, indicating that TAGs or fatty acids from the LDs could be important for cell proliferation. FIT2 disruption was associated with enhanced sensitivity to oxidative stress. Furthermore, we showed that FIT2 deletion yeast cells were significantly attenuated in murine infection models, suggesting an involvement of LDs in the pathobiology of the fungus.
Microbes and Infection 03/2011; 13(7):663-72. · 3.10 Impact Factor
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ABSTRACT: Unsaturated fatty acids (UFA) are essential components of cells. In Saccharomyces cerevisiae, stearoyl-coenzyme A (CoA) desaturase 1 (OLE1) affects cell viability through the regulation of oleic (18:1) or palmitoleic (16:1) acid production. In this study, we used a targeted gene deletion approach to determine the impact of OLE1 on the emerging human pathogenic fungus Candida parapsilosis. We found that the deletion of OLE1 resulted in an auxotrophic yeast strain (designated OLE1 KO) that required unsaturated fatty acids for growth but not saturated fatty acids. Additionally, the production of UFA by OLE1 KO yeast cells was markedly reduced, suggesting that Ole1 is essential for UFA production. In contrast to wild-type C. parapsilosis, which produced pseudohyphal growth on UFA-supplemented medium agar, pseudohyphal formation in the OLE1 KO cells was severely impaired, suggesting that Ole1 regulates morphology. Furthermore, the OLE1 KO cells were hypersensitive to various stress-inducing factors, such as salts, SDS, and H(2)O(2), especially at the physiological temperature. The results indicate that OLE1 is essential for the stress response, perhaps through the production of UFA for cell membrane biosynthesis. The OLE1 KO cells also were hypersensitive to human and fetal bovine serum, suggesting that targeting Ole1 could suppress the dissemination of yeast cells in the bloodstream. Murine-like macrophage J774.16 more efficiently killed the OLE1 KO yeasts, and significantly larger amounts of nitric oxide were detected in cocultures of macrophages and OLE1 KO cells than with wild-type or heterozygous strains. Moreover, the disruption of OLE1 significantly reduced fungal virulence in systemic murine infection. Taken together, these results demonstrate that Ole1 regulates the pathobiology of C. parapsilosis via UFA and that the OLE1 pathway is a promising antifungal target.
Infection and immunity 10/2010; 79(1):136-45. · 4.21 Impact Factor
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ABSTRACT: The yeast Candida parapsilosis is an opportunistic human pathogen frequently associated with nosocomial infections in neonates and patients with diminished immunity. A growing number of studies powered by recent advances in molecular genetics and genomics provide a background for uncovering the molecular basis of its virulence that suggests promising avenues for therapeutic intervention against this pathogen. Importantly, these studies also revealed several unique genetic and physiological features absent in model organisms, such as baker's and fission yeasts. Hence, besides the clinical impact, C. parapsilosis represents an interesting non-conventional model suitable for investigations of several fundamental biological phenomena in cellular physiology, morphogenesis, and genome maintenance. In this study, we provide a concise review on C. parapsilosis biology and highlight its interesting biological features. In addition, we summarize approaches for genetic manipulation, which have enhanced research on this species by overcoming limitations of conventional genetic analysis caused primarily by an apparent absence of a sexual cycle and the diploid state of its genome.
Current Genetics 09/2009; 55(5):497-509. · 2.56 Impact Factor
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ABSTRACT: Histoplasma capsulatum is the most common cause of invasive fungal pulmonary disease worldwide. The interaction of H. capsulatum with a host is a complex, dynamic process. Severe disease most commonly occurs in individuals with compromised immunity, and the increasing utilization of immunomodulators in medicine has revealed significant risks for reactivation disease in patients with latent histoplasmosis. Fortunately, there are well developed molecular tools and excellent animal models for studying H. capsulatum virulence and numerous recent advances have been made regarding the pathogenesis of this fungus that will improve our capacity to combat disease.
Microbes and Infection 08/2008; 10(9):973-7. · 3.10 Impact Factor
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ABSTRACT: The yeast Candida parapsilosis has emerged as a major human pathogen. The fungus is found in diverse environments as well as in different mammalian hosts, indicative of a successful adaptation to various niches. Fatty acids are the building blocks of cell membranes. Thus, the yeast must have evolved efficient ways to assimilate fatty acids from different sources, such as glucose via de novo fatty acid synthesis or lipids via lipolysis. We have recently shown that blocking the fatty acid synthesis pathway or interfering with the production of secreted lipases impeded yeast growth in glucose and lipid-containing media, respectively. However, in a more complex media (e.g. presence of glucose and lipids), blockage of either pathway individually resulted in growth similar to wild-type yeast. Here, we demonstrate that dual inhibition of these pathways significantly decreased yeast growth in complex media. Therefore, we propose that simultaneously targeting secreted lipases and fatty acid pathways might be ideal to combat C. parapsilosis disease and perhaps other pathogenic fungi.
Virulence 2(6):538-41. · 2.26 Impact Factor
