Candida parapsilosis secreted lipase is a major virulence factor
Candida parapsilosis is the second most common cause of invasive candidiasis worldwide. This fungus is particularly associated with disease in premature infants and immunocompromised adults and is a major cause of infections in intensive care units. Despite increasing clinical importance, little is known about the genetic basis of fungal virulence traits that enable C. parapsilosis to cause disease. Virulence factors of C. parapsilosis need to be identified in order to develop more effective therapy against this pathogen. The authors developed a gene deletion system for C. parapsilosis and used it to delete the lipase locus in the C. parapsilosis genome. They also reconstructed the missing genes, which restored lipase activity. Biofilm formation was inhibited with lipase-negative mutants and their growth was significantly reduced in lipid-rich media. The knockout mutants were more efficiently ingested and killed by macrophage-like cells. Additionally, the lipase-negative mutants were significantly less virulent in infection models that involve inoculation of reconstituted human oral epithelium or murine intraperitoneal challenge. These studies represent the first targeted disruption of a gene in C. parapsilosis and show that C. parapsilosis-secreted lipase is involved in disease pathogenesis. This system for targeted gene deletion holds great promise for rapidly enhancing our knowledge of the biology and virulence of this increasingly common invasive fungal pathogen.