The Mechanistic Targets of Antifungal Agents: An Overview

Abstract

Pathogenic fungi are a major causative group for opportunistic infections (OIs). AIDS patients and other immunocompromised individuals are at risk for OIs, which if not treated appropriately, contribute to the mortality associated with their conditions. Several studies have indicated that the majority of HIV-positive patients contract fungal infections throughout the course of their disease. Similar observations have been made regarding the increased frequency of bone marrow and organ transplants, the use of antineoplastic agents, the excessive use of antibiotics, and the prolonged use of corticosteroids among others. In addition, several pathogenic fungi have developed resistance to current drugs. Together these have conspired to spur a need for developing new treatment options for OIs. To aid this effort, this article reviews the biological targets of current and emerging drugs and agents that act through these targets for the treatment of opportunistic fungal infections.

Antifungal Agents in Agriculture: Friends and Foes of Public Health

“…The immune system of a healthy individual has several effective mechanisms to identify, control, and eliminate fungal infections. However, in pathological conditions, including acquired immunodeficiency syndrome (AIDS), tuberculosis, diabetes mellitus, and cancer, or under increased physiological stress, such as during organ transplantation, corticosteroid administration, and chemotherapy [6,7], the risk of developing fungal infections-related ailments is highly increased [8]. Among the infectious fungal species, Aspergillus spp., Candida spp., Cryptococcus spp., and Pneumocystis jirovecii are the causative agents of major mycoses in humans [9,10].…”

“…It is difficult to develop novel fungicides with ideal characteristics, including broad-spectrum effectiveness, enhanced bioavailability, and minimal toxicity and side effects, due to similarities between fungal and mammalian cells, such as in the biosynthetic pathways and chromatin organization of DNA [6,14]. Consequently, drug development against invasive fungal pathogens has been slow.…”

Negative regulation of Candida glabrata Pdr1 by the deubiquitinase subunit Bre5 occurs in a ubiquitin independent manner

“…Especially critical classes of chemotherapeutics are those effective against pathogenic fungi. There are only four antifungal drug classes currently available for use in the clinic consisting of the polyenes, pyrimidine analogues, azoles and echinocandins (reviewed in (Sanglard and Odds, 2002;Mazu et al, 2016)). Azole drugs represent the most commonly used antifungal compound and act by inhibiting biosynthesis of the fungalspecific sterol ergosterol (recently discussed in (Perlin et al, 2017)).…”

Antifungal Properties of Secondary Metabolites of Azadirachta Indica and Lawsonia Inermis – An in Silico Study

“…A few years ago, about 100 methionine auxotrophs have been classified in to different complementation group [6]. The sulfate assimilation pathway is the mechanism involved the interference of amino acid transport and cellular regulation of amino acid metabolism in the fungal organism [7]. Inhibition of induction of sulfite reductase enzyme of sulfate assimilation pathway was found to be the major cause of SA inhibition [8].…”