Sphingolipidomics of drug resistant Candida auris clinical isolates reveal distinct sphingolipid species signatures

Mohit Kumar,Ashutosh Singh,Sonam Kumari,Praveen Kumar,Mohd Wasi,Alok K Mondal,Shivaprakash M Rudramurthy,Arunaloke Chakrabarti,Naseem A Gaur,Neil A.R Gow,Rajendra Prasad

doi:10.1016/j.bbalip.2020.158815

Abstract

Independent studies from our group and others have provided evidence that sphingolipids (SLs) influence the antimycotic susceptibility of Candida species. We analyzed the molecular SL signatures of drug-resistant clinical isolates of Candida auris, which have emerged as a global threat over the last decade. This included Indian hospital isolates of C. auris, which were either resistant to fluconazole (FLCR) or amphotericin B (AmBR) or both drugs. Relative to Candida glabrata and Candida albicans strains, these C. auris isolates were susceptible to SL pathway inhibitors such as myriocin and aureobasidin A, suggesting that SL content may influence azole and AmB susceptibilities. Our analysis of SLs confirmed the presence of 140 SL species within nine major SL classes, namely the sphingoid bases, Cer, αOH-Cer, dhCer, PCer, αOH-PCer, αOH-GlcCer, GlcCer, and IPC. Other than for αOH-GlcCer, most of the SLs were found at higher concentrations in FLCR isolates as compared to the AmBR isolates. SLs were at intermediate levels in FLCR + AmBR isolates. The observed diversity of molecular species of SL classes based on fatty acyl composition was further reflected in their distinct specific imprint, suggesting their influence in drug resistance. Together, the presented data improves our understanding of the dynamics of SL structures, their synthesis, and link to the drug resistance in C. auris.

Highlights

Increasing antimicrobial resistance in pathogenic fungi is becoming a global health threat and eroding our ability to control fungal infections with a limited armamentarium of antifungals [1]
Most of the fungal infections associated with significant mortality and antimicrobial resistance are triggered by opportunistic human fungal pathogens [1,2]
The Minimum inhibitory concentrations (MIC) of all the isolates used in this study were measured against two antifungals, namely amphotericin B (AmB) and FLC

Summary

Introduction

Increasing antimicrobial resistance in pathogenic fungi is becoming a global health threat and eroding our ability to control fungal infections with a limited armamentarium of antifungals [1]. Most of the fungal infections associated with significant mortality and antimicrobial resistance are triggered by opportunistic human fungal pathogens [1,2]. The major pathogens, Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans, may survive in anatomically distinct locations within the host and are capable of fostering deepseated infections in patients with compromised immune systems [3]. In contrast to the common C. albicans, non-albicans Candida (NAC) species are evolving as problematic drug resistance pathogens [1]. The recent emergence of multiple drug-resistant Candida auris clades within a short. Amity Institute of Integrative Science and Health, Amity University Gurgaon, Haryana, India

Methods

Results

Conclusion