Abrogation of pathogenic attributes in drug resistantCandida aurisstrains by farnesol

Abstract

<jats:title>Abstract</jats:title><jats:p><jats:italic>Candida auris</jats:italic>, a decade old <jats:italic>Candida</jats:italic> 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 <jats:italic>Candida</jats:italic> species, including <jats:italic>C. auris</jats:italic>. Therefore, targeting these factors may prove an effective approach to combat MDR in <jats:italic>C. auris</jats:italic>. In this study, 25 clinical isolates of <jats:italic>C. auris</jats:italic> from different hospitals of South Africa were used. All the isolates were found capable enough to form biofilms on 96-well 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 <jats:italic>C. auris</jats:italic>. The MIC for planktonic cells ranged from 62.5-125 mM and for sessile cells was 125 mM (0 h and 4 h biofilm) and 500 mM (12 h and 24 h biofilm). Farnesol inhibited biofilm formation, blocked efflux pumps and downregulated biofilm- and efflux pump-associated genes. Modulation of <jats:italic>C. auris</jats:italic> biofilm formation and efflux pump activity by farnesol represent a promising approach for controlling life threatening infections caused by this pathogen.</jats:p>

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 associated genes at a concentration of 125 mM ( Figure 23 ).…”