title: Drug resistance mechanisms and their regulation in non-albicans Candida species.
abstract: Fungal pathogens use various mechanisms to survive exposure to drugs. Prolonged treatment very often leads to the stepwise acquisition of resistance. The limited number of antifungal therapeutics and their mostly fungistatic rather than fungicidal character facilitates selection of resistant strains. These are able to cope with cytotoxic molecules by acquisition of appropriate mutations, re-wiring gene expression and metabolic adjustments. Recent evidence points to the paramount importance of the permeability barrier and cell wall integrity in the process of adaptation to high drug concentrations. Molecular details of basal and acquired drug resistance are best characterized in the most frequent human fungal pathogen, Candida albicans Effector genes directly related to the acquisition of elevated tolerance of this species to azole and echinocandin drugs are well described. The emergence of high-level drug resistance against intrinsically lower susceptibility to azoles in yeast species other than C. albicans is, however, of particular concern. This is due to their steadily increasing contribution to high mortality rates associated with disseminated infections. Recent findings concerning underlying mechanisms associated with elevated drug resistance suggest a link to cell wall and plasma membrane metabolism in non-albicans Candida species.
authors.affiliation: Department of Biochemistry, Pharmacology and Toxicology, Wroclaw University of Environmental and Life Sciences, Norwida 31, PL 50-375, Wroclaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kołaczkowska
authors.affiliation: Department of Biophysics, Wroclaw Medical University, Chalubinskiego 10, PL50-368, Wroclaw, Poland mkolacz2@poczta.onet.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kołaczkowski
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects*; D025141:Drug Resistance, Fungal; D015966:Gene Expression Regulation, Fungal; D006801:Humans
chemical_list: D000935:Antifungal Agents