Combinatorial drug approaches to tackleCandida albicansbiofilms

Abstract

The human fungal opportunistic pathogen Candida albicans resides in the human gut, genitourinary tract and on the skin. The majority of infections caused by C. albicans are biofilm-related. In the first part of this review, we discuss new insights into C. albicans biofilm characteristics, concentrating on the extracellular matrix, phenotypic switching, efflux pumps and persister cells. It is widely accepted that this multicellular lifestyle is more resistant to traditional antifungal treatment compared to free-living cells. Therefore, much effort is put in the search for combinations of drugs leading to synergistic interactions against microbial biofilms to achieve lower effective doses of the drugs. In the second part of this manuscript, we review all recently identified compounds that act synergistically with azoles, echinocandins and/or polyenes against C. albicans biofilms.

Quercetin Assists Fluconazole to Inhibit Biofilm Formations of Fluconazole-Resistant Candida Albicans in In Vitro and In Vivo Antifungal Managements of Vulvovaginal Candidiasis

“…Combinatorial therapy has become a universal approach in the prevention and management of C. albicans biofilms [37]. C. albicans biofilms represent a new type of mode of fungal survival and confer to fungal pathogen greater resistance that was even up to hundreds of folds greater than their planktonic counterparts, resulting in single use of currently available antifungal agents futile.…”

A Linear 19-Mer Plant Defensin-Derived Peptide Acts Synergistically with Caspofungin against Candida albicans Biofilms

“…Only few conventional antimycotics, such as echinocandins (e.g., caspo-, mica-, and anidulafungin) and liposomal formulations of amphotericin B, can be used to treat such fungal biofilm-related infections (Fiori et al, 2011 ; Uppuluri et al, 2011 ). However, there are drawbacks associated with these antimycotics, including their costs, toxicity and/or resistance occurrence (De Cremer et al, 2015 ; Tsui et al, 2016 ). Therefore, there is a need for the identification and characterization of novel antifungal agents, which are also effective against fungal biofilms.…”

“…Therefore, there is a need for the identification and characterization of novel antifungal agents, which are also effective against fungal biofilms. An alternative strategy to combat fungal biofilms is combination therapy in which two compounds with different mode of actions are combined (De Cremer et al, 2015 ). Many advantages are associated with these combination therapies over mono therapies, such as (i) broadening spectrum of drug activity, (ii) synergy, (iii) lowered effective doses, (iv) reduced risk of resistance occurrence, and (v) more rapid antifungal effects (Mukherjee et al, 2005 ; Fohrer et al, 2006 ; Bink et al, 2011 ).…”

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).…”