The phosphatome of opportunistic pathogen Candida species
Krisztina Szabó, Márton Miskei, Ilona Farkas, Viktor Dombrádi
Abstract
Several Candida species, the best known example of which is Candida albicans, are opportunistic human pathogens that are responsible for frequent nosocomial infections. A worrisome aspect of the currently available treatments of candidemia is the steady development of resistance to antifungals among these potentially life threatening fungi. Under these circumstances the search for novel drug targets is a well justified research direction. We propose that the principles of signal transduction therapy by targeting protein phosphatases can be adopted as these enzymes carry out important physiological functions in Candida. We demonstrate that C. tropicalis, C. albicans, C. dubliniensis, and S. cerevisiae exhibit the largest repertoire of protein phosphatases among the investigated fungi. Together with other opportunistic pathogen Candida species and the members of the Saccharomycetales order, they expanded their phosphatome by repeated gene duplications. We noted that evolution generated a set of fungus specific phosphatases which can be targeted without the danger of causing undesirable side effects in the human body. Based on the conflicting criteria of effectiveness and selectivity, we identified and characterized 7 phosphatases that are potent virulence determinants and may be utilized as potential antifungal drug targets.