ABC Transporter Genes Show Upregulated Expression in Drug Resistant Clinical Isolates of Candida auris : a Genome-Wide Characterization of ATP-Binding Cassette (ABC) Transporter Genes

Funding This work was supported by the ICMR (AMR/149/2018-ECD-II) and DBT (BT/PR14117/BRB/10/1420/2015) to RP. AKM appreciates the support by research grant EMR/2016/001927 and DST PURSE II from the Department of Science and Technology (IN). MW was grateful for a Senior Research Fellowship from the University Grant Commission. NG acknowledges the Wellcome Trust support of a Senior Investigator (101873/Z/13/Z), Collaborative (200208/A/15/Z), and Strategic Awards (097377/Z11/Z), and the MRC Centre for Medical Mycology (MR/N006364/1). AJM was supported by the University of Aberdeen studentship. Work in AL’s laboratory was supported by the Wellcome Trust (212524/Z/18/Z) and the Medical Research Council (MRC) Centre for Medical Mycology at the University of Aberdeen (MR/P501955/1 and MR/N006364/1). Acknowledgments We thank the Centre for Genome Enabled Biology and Medicine at the University of Aberdeen (E. Collie-Duguid and S. Shaw) for sequencing and support with genome analysis.Peer reviewedPublisher PD

Identification of genome-wide binding sites of heat shock factor 1, Hsf1, under basal conditions in the human pathogenic yeast, Candida albicans

Abstract The master regulator of thermal stress response, Hsf1, is also an essential determinant for viability and virulence in Candida albicans. Our recent studies highlighted that apart from ubiquitous roles of Hsf1 at higher temperatures, it also has myriad non-heat shock responsive roles essential under iron deprivation and drug defense. Here, we further explored its implications in the normal cellular functioning, by profiling its genome-wide occupancy using chromatin immuno-precipitation coupled to high-density tiling arrays under basal and iron deprived conditions. Hsf1 recruitment profiles revealed that it binds to promoters of 660 genes of varied functions, under both the conditions, however, elicited variability in intensity of binding. For instance, Hsf1 binding was observed on several genes of oxidative and osmotic stress response, cell wall integrity, iron homeostasis, mitochondrial, hyphal and multidrug transporters. Additionally, the present study divulged a novel motif under basal conditions comprising, -GTGn3GTGn3GTG- where, Hsf1 displays strong occupancy at significant number of sites on several promoters distinct from the heat induced motif. Hence, by binding to and regulating major chaperones, stress responsive genes and drug resistance regulators, Hsf1 is imperative in regulating various cellular machineries. The current study provides a framework for understanding novel aspects of how Hsf1 coordinates diverse cellular functions

Essential oils and their active compounds potentially useful in the fight against Candida auris

The anti-fungal activity of 15 EOs (Pranarom International, Belgique) was tested against 10 clinical fluconazole-resistant strains of C. auris. Micro-broth dilution (MBD) test, according to EUCAST guidelines, was performed to select the most active EOs by identifying the Minimal Inhibitory Concentration 90 (MIC90) and Minimal Fungicidal Concentration 90 (MFC90). Both Cinnamomum zeylanicum (CZ) from bark and Coriandrum sativum (CS) EOs were first chemically characterized by using gas-chromatography/mass-spectrometry (GC/MS) and then fractionated with petroleum ether/ethyl acetate and petroleum ether/methanol with different ratios, respectively, to obtain 3 fractions/EO. The chemical quality and the antimicrobial activity of each fraction were evaluated using the aforementioned GC-MS and MBD tests. Once identified the active fraction of each EO, MBD tests were repeated by using the chemical compounds (linalool, cinnamaldheyde, eugenol and camphor isolated from vegetables) of each active fraction. Finally, the synergy between fluconazole and the CZ-OE was evaluated using the checkerboard test. The EOs of CZ and CS showed the lowest values of MIC90 (0.25 % v/v and 0.015% v/v respectively) and MFC90 (0.5% v/v and 0.06% v/v respectively) (fig.1). CZ-EO was mainly composed of cinnamaldheyde (66.0%), while CS-EO of linalool (31.2%) and 2-decenal (18.8%). For both EOs, the second fraction was the most active, and that of CZ-EO was composed of 4 compounds (linalool, cinnamaldheyde, eugenol and cynnamil acetate), while that of CS-EO of only two compounds (linalool and camphor). Cinnamaldehyde and linalool were the active compounds of CZ-EO and CS-EO respectively; they show the same MIC90 and MFC90 values as their corresponding EOs. Fluconazole at a concentration of 8 ug/ml showed synergy with CZOE (concentration of 0.03% v/v)