TY - JOUR
T1 - Novel approaches for efficient antifungal drug action
AU - Lee, Heejeong
AU - Lee, Dong Gun
N1 - Publisher Copyright:
© 2018 by The Korean Society for Microbiology and Biotechnology.
PY - 2018/11/28
Y1 - 2018/11/28
N2 - The emergence of multidrug-resistant microorganisms, as well as fungal infectious diseases that further threaten health, especially in immunodeficient populations, is a major global problem. The development of new antifungal agents in clinical trials is inferior to the incidence of drug resistance, and the available antifungal agents are restricted. Their mechanisms aim at certain characteristics of the fungus in order to avoid biological similarities with the host. Synthesis of the cell wall and ergosterol are mainly targeted in clinical use. The need for new approaches to antifungal therapeutic agents or development alternatives has increased. This review explores new perspectives on mechanisms to effectively combat fungal infections and effective antifungal activity. The clinical drug have a common feature that ultimately causes caspase-dependent cell death. The drugs-induced cell death pathway is associated with mitochondrial dysfunction, including mitochondrial membrane depolarization and cytochrome c release. This mechanism of action also reveals antimicrobial peptides, the primary effector molecules of innate systems, to highlight new alternatives. Furthermore, drug combination therapy is suggested as another strategy to combat fungal infection. The proposal for a new approach to antifungal agents is not only important from a basic scientific point of view, but will also assist in the selection of molecules for combination therapy.
AB - The emergence of multidrug-resistant microorganisms, as well as fungal infectious diseases that further threaten health, especially in immunodeficient populations, is a major global problem. The development of new antifungal agents in clinical trials is inferior to the incidence of drug resistance, and the available antifungal agents are restricted. Their mechanisms aim at certain characteristics of the fungus in order to avoid biological similarities with the host. Synthesis of the cell wall and ergosterol are mainly targeted in clinical use. The need for new approaches to antifungal therapeutic agents or development alternatives has increased. This review explores new perspectives on mechanisms to effectively combat fungal infections and effective antifungal activity. The clinical drug have a common feature that ultimately causes caspase-dependent cell death. The drugs-induced cell death pathway is associated with mitochondrial dysfunction, including mitochondrial membrane depolarization and cytochrome c release. This mechanism of action also reveals antimicrobial peptides, the primary effector molecules of innate systems, to highlight new alternatives. Furthermore, drug combination therapy is suggested as another strategy to combat fungal infection. The proposal for a new approach to antifungal agents is not only important from a basic scientific point of view, but will also assist in the selection of molecules for combination therapy.
KW - Antifungal drugs
KW - Antimicrobial peptide
KW - Azoles
KW - Drug combination
KW - Polyenes
KW - Programmed cell death
UR - http://www.scopus.com/inward/record.url?scp=85058871611&partnerID=8YFLogxK
U2 - 10.4014/jmb.1807.07002
DO - 10.4014/jmb.1807.07002
M3 - Review article
C2 - 30178649
AN - SCOPUS:85058871611
SN - 1017-7825
VL - 28
SP - 1771
EP - 1781
JO - Journal of Microbiology and Biotechnology
JF - Journal of Microbiology and Biotechnology
IS - 11
ER -