Candida albicans mutant construction and characterization of selected virulence determinants

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Candida albicans mutant construction and characterization of selected virulence determinants

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Candida albicans is a diploid, polymorphic yeast that grows as budding cells which can extend to the mycelial state (i.e. hyphae and/or pseudohyphae) under favorable conditions (Kurtzman, 2011). C. albicans is readily isolated from human clinical samples due to its commensal lifestyle (Cooper, 2011), and, unlike non-pathogenic yeasts, is less frequently isolated from the environment outside its host. As a pathogen, it accounts for a large number of fungal infections occurring in the digestive tract, mucocuteneous tissues and skin as well as in the bloodstream. Furthermore, C. albicans is responsible for 40% of device-associated infections in the United States of America due to biofilm development on medical devices and their inherent resistance to antimicrobial therapy (Wenzel, 1995, Rueping et al., 2009). Infected individuals are, in most cases, immune deficient and/or immune suppressed due to conditions such as AIDS or critical illness. The ability of C. albicans to cause infections is largely attributed to a number of virulence factors including acquired resistance towards antimicrobial drugs such as the azoles and polyenes, and to a broad extent, its polyphenic nature which allows it to navigate the dynamic host environmental conditions such as varying temperatures, pH, stress (e.g. oxidative, nitrosative, osmotic, heavy metal and cell wall stress), carbon dioxide levels and available nutrient sources (e.g. carbon, nitrogen, phosphorus or sulfur sources). In addition, other virulence factors such as attachment to the human mucosa and secretion of lipolytic or proteolytic enzymes further contribute to the ability of C. albicans to invade host tissues and cause infections (Calderone and Fonzi, 2001, Nobile et al., 2012).

Gene deletion studies contribute largely to constructed mutant libraries utilized by researchers to study the genetic components underlying virulence of C. albicans (Homann et al., 2009, Pérez et al., 2013). Since construction of these mutants, it is now possible to conduct an assessment of specific genetic determinants and their effect on cellular activities employed by C. albicans to thrive in the mammalian host. In this review the emphasis will be placed on the common gene deletion methods routinely used to create C. albicans mutant strains. Furthermore, in vitro characterization of some of the important genetic determinants in Candida biology will also be highlighted.



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