Mechanisms of Antifungal Drug Resistance.
Antifungal therapy is a central component of patient management for acute and chronic mycoses. Yet, treatment choices are restricted because of the sparse number of antifungal drug classes. Clinical management of fungal diseases is further compromised by the emergence of antifungal drug resistance, which eliminates available drug classes as treatment options. Once considered a rare occurrence, antifungal drug resistance is on the rise in many high-risk medical centers. Most concerning is the evolution of multidrug- resistant organisms refractory to several different classes of antifungal agents, especially among common Candida species. The mechanisms responsible are mostly shared by both resistant strains displaying inherently reduced susceptibility and those acquiring resistance during therapy. The molecular mechanisms include altered drug affinity and target abundance, reduced intracellular drug levels caused by efflux pumps, and formation of biofilms. New insights into genetic factors regulating these mechanisms, as well as cellular factors important for stress adaptation, provide a foundation to better understand the emergence of antifungal drug resistance.
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Leah E
LE
Cowen
University of Lausanne and University Hospital Center, Institute of Microbiology, 1011 Lausanne, Switzerland.
Dominique
D
Sanglard
University of Liverpool, Sherrington Building, Ashton Street, Liverpool L69 3GE, United Kingdom.
Susan J
SJ
Howard
College of Pharmacy, The University of Tennessee Health Science Center, Memphis, Tennessee 38163.
P David
PD
Rogers
Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103.
David S
DS
Perlin
D000935:Antifungal Agents / Q000145:classification / Q000627:therapeutic use*; D018441:Biofilms / Q000187:drug effects*; D025141:Drug Resistance, Fungal / Q000235:genetics*; D006801:Humans; D009181:Mycoses / Q000382:microbiology*; D020871:RNA Stability
D000935:Antifungal Agents