ABC transportome inventory of human pathogenic yeast Candida glabrata: Phylogenetic and expression analysis

Sonam Kumari; Mohit Kumar; Nitesh Kumar Khandelwal; Priya Kumari; Mahendra Varma; Poonam Vishwakarma; Garima Shahi; Suman Sharma; Andrew M Lynn; Rajendra Prasad; Naseem A Gaur

doi:10.1371/journal.pone.0202993

ABC transportome inventory of human pathogenic yeast Candida glabrata: Phylogenetic and expression analysis

PLoS One. 2018 Aug 28;13(8):e0202993. doi: 10.1371/journal.pone.0202993. eCollection 2018.

Authors

Affiliations

¹ Yeast Biofuel Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
² Amity Institute of Integrative Science and Health, Amity University Gurgaon, Haryana, India.
³ School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, India.

Abstract

ATP-binding cassette (ABC) is one of the two major superfamilies of transporters present across the evolutionary scale. ABC superfamily members came to prominence due to their ability to extrude broad spectrum of substrates and to confer multi drug resistance (MDR). Overexpression of some ABC transporters in clinical isolates of Candida species was attributed to the development of MDR phenotypes. Among Candida species, Candida glabrata is an emerging drug resistant species in human fungal infections. A comprehensive analysis of such proteins in C. glabrata is required to untangle their role not only in MDR but also in other biological processes. Bioinformatic analysis of proteins encoded by genome of human pathogenic yeast C. glabrata identified 25 putative ABC protein coding genes. On the basis of phylogenetic analysis, domain organization and nomenclature adopted by the Human Genome Organization (HUGO) scheme, these proteins were categorized into six subfamilies such as Pleiotropic Drug Resistance (PDR)/ABCG, Multi Drug Resistance (MDR)/ABCB, Multi Drug Resistance associated Protein (MRP)/ABCC, Adrenoleukodystrophy protein (ALDp)/ABCD, RNase L Inhibitor (RLI)/ABCE and Elongation Factor 3 (EF3)/ABCF. Among these, only 18 ABC proteins contained transmembrane domains (TMDs) and were grouped as membrane proteins, predominantly belonging to PDR, MDR, MRP, and ALDp subfamilies. A comparative phylogenetic analysis of these ABC proteins with other yeast species revealed their orthologous relationship and pointed towards their conserved functions. Quantitative real time PCR (qRT-PCR) analysis of putative membrane localized ABC protein encoding genes of C. glabrata confirmed their basal expression and showed variable transcriptional response towards antimycotic drugs. This study presents first comprehensive overview of ABC superfamily proteins of a human fungal pathogen C. glabrata, which is expected to provide an important platform for in depth analysis of their physiological relevance in cellular processes and drug resistance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP-Binding Cassette Transporters / chemistry
ATP-Binding Cassette Transporters / genetics*
ATP-Binding Cassette Transporters / metabolism
Candida glabrata / genetics*
Chromosomes, Fungal / genetics
Gene Expression Profiling*
Humans
Phylogeny*
Protein Domains

Substances

ATP-Binding Cassette Transporters

Grants and funding

The work has been supported in parts by grants to R.P. from the Department of Biotechnology DBT [No. BT/01/CEIB/10/III/02], DBT [No. BT/PR7392/MED/29/652/2012] and DBT [No. BT/PR14117/BRB/10/1420/2015] and in parts by grants to N.A.G. by DST Ramanujan Fellowship grant [SR/S2/RJN-07/2012], DBT grants [No. BT/PR10684/PBD/26/403/2013] and DBT [No. BT/PB/Centre/03/2011]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.