Reactive Oxygen Species-Inducing Antifungal Agents and Their Activity Against Fungal Biofilms

Abstract

Invasive fungal infections are associated with very high mortality rates ranging from 20-90% for opportunistic fungal pathogens such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. Fungal resistance to antimycotic treatment can be genotypic (due to resistant strains) as well as phenotypic (due to more resistant fungal lifestyles, such as biofilms). With regard to the latter, biofilms are considered to be critical in the development of invasive fungal infections. However, there are only very few antimycotics, such as miconazole (azoles), echinocandins and liposomal formulations of amphotericin B (polyenes), which are also effective against fungal biofilms. Interestingly, these antimycotics all induce reactive oxygen species (ROS) in fungal (biofilm) cells. This review provides an overview of the different classes of antimycotics and novel antifungal compounds that induce ROS in fungal planktonic and biofilm cells. Moreover, different strategies to further enhance the antibiofilm activity of such ROS-inducing antimycotics will be discussed.

Artemisinins, New Miconazole Potentiators Resulting in Increased Activity against Candida albicans Biofilms

“…However, it has been reported that biofilm formation typically induces several stress response pathways that impair the activity of azole drugs, such as the induction of drug efflux pumps (17). Consequently, cells in a biofilm are up to 1,000-fold more azole resistant than their planktonic counterparts (1,18), supporting the need for new treatments.…”

Identification of survival-promoting OSIP108 peptide variants and their internalization in human cells

“…C. albicans is the predominant human fungal pathogen and accounts for 35% of invasive fungal infections (Lewis et al, 2013). C. albicans cells can also grow as a surface-attached biofilm, e.g., on catheters and heart valves, thereby causing recurrent systemic infections (Cuéllar-Cruz et al, 2012;Mayer et al, 2013), which are in general resistant to most antimycotics (De Cremer et al, 2015;Delattin et al, 2014a). In the search for novel antibiofilm molecules, we previously identified OSIP108 as a new antibiofilm peptide (Delattin et al, 2014c).…”

Oxy-nitroso shielding burst model of cold atmospheric plasma therapeutics

“…[3,62] Anti-cancer agents (other than CAP) that act by raising tumor oxidative stress include radiotherapy [63]; photodynamic therapy [64]; many chemotherapeutic drugs [65,66]; and hyperthermia [67,68]. Antiinfective drugs, including many antibiotics [69]; antifungals [70]; and anti-parasitics [71] are known to act, at least in part, by raising oxidative stress in infected cells. From the perspective of this article, these drugs may act by triggering or initiating endogenous RONS and achieve their therapeutic effects via oxynitroso shielding, thus matching part of the cell's own stress response mechanism that can lead to either cellular apoptosis or adaptation.…”