Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris

Abstract

Invasive fungal infections represent an expanding threat to public health. During the past decade, a paradigm shift of candidiasis from Candida albicans to non-albicans Candida species has fundamentally increased with the advent of Candida auris. C. auris was identified in 2009 and is now recognized as an emerging species of concern and underscores the urgent need for novel drug development strategies. In this review, we discuss the genomic epidemiology and the main virulence factors of C. auris. We also focus on the different new strategies and results obtained during the past decade in the field of antifungal design against this emerging C. auris pathogen yeast, based on a medicinal chemist point of view. Critical analyses of chemical features and physicochemical descriptors will be carried out along with the description of reported strategies.

Unpredictable In Vitro Killing Activity of Amphotericin B against Four Candida auris Clades

“…These data suggest that the efficacy of AMB for the treatment of invasive C. auris infections, including meningitis, endophthalmitis, and urinary tract infections, cannot be reliably predicted using MIC results, which may explain the high mortality with AMB treatment [ 3 , 4 ]. Although a combination of echinocandins with AMB may improve survival [ 13 ], the discovery of new antifungal agents with traditional or new targets is essential to improve the survival rate of infections by multiresistant fungi, including C. auris [ 24 , 25 , 26 ].…”

Disruption of Iron Homeostasis and Mitochondrial Metabolism Are Promising Targets to Inhibit Candida auris

“…This yeast emerged as a human pathogen nearly simultaneously in different geographical locations subdivided into four genetically distinct clades, with a potential fifth one discovered recently ( 4 , 5 ). C. auris is a nosocomial pathogen with a mortality rate of 30% to 70% ( 6 – 8 ). In contrast to other Candida species, this fungus is a strong colonizer of the human skin, which facilitates transmissions between patients ( 9 , 10 ).…”

Two New Compounds Containing Pyridinone or Triazine Heterocycles Have Antifungal Properties against Candida albicans

“…C. albicans is the most commonly identified Candida species in clinical settings and is one of the leading causes of hospital-acquired infections. Antifungal resistance is an emerging problem worldwide and this complicates the selection of appropriate antifungal therapy [ 3 , 4 ]. A subset of Candida strains are now resistant to first-line antifungal agents such as fluconazole and echinocandins [ 4 ].…”