Abrogation of pathogenic attributes in drug resistant Candida auris strains by farnesol

Abstract

Candida auris, a decade old Candida species, has been identified globally as a significant nosocomial multidrug resistant (MDR) pathogen responsible for causing invasive outbreaks. Biofilms and overexpression of efflux pumps such as Major Facilitator Superfamily and ATP Binding Cassette are known to cause multidrug resistance in Candida species, including C. auris. Therefore, targeting these factors may prove an effective approach to combat MDR in C. auris. In this study, 25 clinical isolates of C. auris from different hospitals of South Africa were used. All the isolates were found capable enough to form biofilms on 96-well flat bottom microtiter plate that was further confirmed by MTT reduction assay. In addition, these strains have active drug efflux mechanism which was supported by rhodamine-6-G extracellular efflux and intracellular accumulation assays. Antifungal susceptibility profile of all the isolates against commonly used drugs was determined following CLSI recommended guidelines. We further studied the role of farnesol, an endogenous quorum sensing molecule, in modulating development of biofilms and drug efflux in C. auris. The MIC for planktonic cells ranged from 62.5-125 mM, and for sessile cells was 125 mM (4h biofilm) and 500 mM (12h and 24h biofilm). Furthermore, farnesol (125 mM) also suppresses adherence and biofilm formation by C. auris. Farnesol inhibited biofilm formation, blocked efflux pumps and downregulated biofilm-and efflux pump-associated genes. Modulation of C. auris biofilm formation and efflux pump activity by farnesol represent a promising approach for controlling life threatening infections caused by this pathogen.

Antifungal Resistance in Candida auris: Molecular Determinants

“…Besides, the combination of carvacrol reduced the MIC values of antifungals [17]. Farnesol has shown significant inhibition of planktonic cell growth in C. auris at concentrations ranging from 0.3 to 62.5 mM within 24 h [15,100]. With regards to the in vivo experiments, daily treatment with 75 mM of farnesol decreased the fungal load in an immunosuppressed murine model with disseminated candidiasis, especially in the case of pre-exposed inoculums to farnesol [15].…”

“…Both carvacrol and farnesol inhibit cell adherence and biofilm formation, mitigating Candida spp. virulence [15,17,100]. Based on this evidence, phenolic compounds can be said to have an alternative or adjuvant therapeutic potential in conventional treatments to control life-threatening infections caused by C. auris.…”

Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris

“…Farnesol, an endogenous quorum sensing molecule, was reported in 2020 by Vartika and Aijaz [130] for its ability to modulate development of biofilms and drug efflux in C. auris. Farnesol also blocked efflux pumps and downregulated biofilm and efflux pump Taken together, these results demonstrated that naturally derivated polymers such as chitosan could be interesting alternatives to conventional antifungals.…”

Candida auris: A Quick Review on Identification, Current Treatments, and Challenges

“…One of the promising approaches seems to be synergistic interactions of compounds with antifungals ( Table 2 ). Published data have also focused on the combination therapy as alternative approaches with antifungal drugs open new insights in the management of a global threat of this multidrug-resistant C. auris, as described by Srivastava et al [ 98 ]. In this study, farnesol, a quorum-sensing molecule, suppressed biofilm formation, blocked efflux pumps, and downregulated biofilm and efflux pump-associated genes.…”

“…In this study, farnesol, a quorum-sensing molecule, suppressed biofilm formation, blocked efflux pumps, and downregulated biofilm and efflux pump-associated genes. Farnesol has been indicated as a promising agent to fight a significant nosocomial multidrug-resistant (MDR) pathogen responsible for causing invasive outbreaks [ 98 ]. Similarly, carvacrol, the most active phenolic compound, displayed both antifungal activity with low MIC for clinical isolates of C. auris and a synergistic effect in combination with Flu, AmB, caspofungin, and micafungin, reducing the MIC value of these drugs as well.…”