Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal Agents: An Overview about Endemic Dimorphic Fungi

Abstract

Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses. Alternative novel drug targets have been investigated; these include metabolic routes used by fungi during infection, such as trehalose and amino acid metabolism and mitochondrial proteins. An overview of new antifungal agents, including nanostructured antifungals, as well as of repositioning approaches is discussed. Studies focusing on the development of vaccines against antifungal diseases have increased in recent years, as these strategies can be applied in combination with antifungal therapy to prevent posttreatment sequelae. Studies focused on the development of a pan-fungal vaccine and antifungal drugs can improve the treatment of immunocompromised patients and reduce treatment costs.

AHistoplasma capsulatumlipid metabolic map identifies antifungal targets

“…1b and Supplementary Tab. [1][2][3][4][5][6][7][8]. The most diverse subclasses of lipids in terms of number of identified lipids were triacylglycerols (TG), phosphatidylcholines (PC) and phosphatidylethanolamine (PE) with 130, 57 and 51 individual species, respectively (Fig.…”

Cross kingdom analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets to ameliorate fungal pathogenicity?

“…This in turn has a significant effect on the triggering of important virulence traits, like the production of hyphae, biofilm growth, capsule formation in C. neoformans, and melanisation [56]. Moreover, metabolic pathways influence fungal vulnerability to innate immune defences and can regulate susceptibility to antifungal drugs [57]. Not only primary metabolism, secondary metabolism results in the release of various secondary metabolites and toxins, such as gliotoxin, aflatoxin, and candidalysin [58,59].…”

Introductory Chapter: Fusarium: Pathogenicity, Infections, Diseases, Mycotoxins and Management

“…Conversely, the echinocandins are lipopeptide molecules which effectively work by inhibiting 1,3-β-D-glucan synthase of the fungal membrane. If a change occurs in the amino acid residues of β-1,3-glucan synthase enzyme subunits (FKS subunits) in the treatment process, it may lead to increased drug resistance [41,42]. Introductory Chapter: Fusarium -Pathogenicity, Infections, Diseases, Mycotoxins and Management http://dx.doi.org/10.5772/intechopen.76507 species level is not easy.…”