Identification of ABC transporter Cdr1 inhibitors of Candida glabrata

Candida glabrata is one of the most common causes of invasive candidiasis. Rising treatment failures from resistance to current antifungal drugs highlight the need for new antifungals. Overexpression of efflux pump transporter genes is significantly associated with the development of multidrug resistance. In this study, we have identified novel and potential inhibitors of ABC transporter Cdr1 of Candida glabrata (CgCdr1) by employing high throughput virtual screening of large chemical datasets from five different chemical libraries (ZINC, DrugBank, ChemDiv antifungal, ChemDiv Kinases, and ChEMBL bioassay). As a result many molecules were predicted to have higher binding affinity toward the CgCdr1, in which a naturally occurring compound, pentagalloyl glucose, was identified to significantly reduce the growth of Candida glabrata with an IC50 value of 16.97 +/- 2.1 mu M. Molecular dynamics studies showed stable binding of pentagalloyl glucose with CgCdr1 protein. In summary, our research identifies pentagalloyl glucose as a novel antifungal compound that has the potential to be used for inhibiting the growth of Candida glabrata.