Human Mycoses: Drugs and Targets for Emerging Pathogens

Population genomics of drug resistance in Candida albicans

“…The evolution of antifungal drug resistance now poses a growing public health problem because of the sharp increase in the incidence of opportunistic fungal infections in recent years (2,3). Currently available antifungal drugs have a limited number of targets, primarily ergosterol and its biosynthesis, nucleic acid synthesis, and cell wall synthesis (4,5).…”

Sterols in erg mutants of Phycomyces: metabolic pathways and physiological effects

“…The remaining mutant, H25, seems to be a regulatory mutant: it accumulates ergosterol amounts like the wild type strain, but the levels of metabolites 6 and 14 increase whilst the levels of triterpenoids 1-3 diminish. The polyene antibiotics nystatin and amphotericin B are fungicidal because they interact with ergosterol in fungal membranes leading to increased membrane permeability, leakage of cytoplasmic contents and cell death [1]. Thereby, the polyene antibiotic resistance shown by the H23 mutant can be attributed to the lack of ergosterol.…”

“…In this way, the presumable involvement of the sterol C-24 methyltransferase (step a, Scheme 1) in a repression mechanism of the fungal sterol biosynthesis is noteworthy, because this enzyme is unique to fungi and, thus, it has been recognized as a particularly attractive drug target [1]. The precise knowledge of this mechanism could facilitate the development of novel and more selective antifungal drugs.…”

“…The main groups of antifungal compounds in clinical use all interact with or inhibit ergosterol, the major sterol in the fungal plasma membrane [1]. An exact understanding of fungal ergosterol biosynthesis and metabolism is therefore crucial for the design of novel, more specific and more effective antifungal drugs.…”

Isolation and identification of antimicrobial agent-producing bacterium from Taxus baccata rhizosphere antagonistic against clinically significant microbes

“…Only pyrrolnitrin antibiotics produced by some fl uorescent pseudomonads have been primarily used as a clinical antifungal agent for treatment of skin mycoses against dermatophytic fungi like Trichophyton 13 . The abundance of P. fl uorescence in the plant rhizosphere is correlated with the importance of their rhizospheric 15 . Many compounds such as phenazines, pyoluteorin, pyrrolnitrin, tropolone, pycocayanin and bulbiformin are produced by Pseudomonas fl uorescence having activity against many bacteria and fungi.…”