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.
Highlights
ATP-binding cassette (ABC) superfamily known as ‘Traffic ATPases’ is very diverse and well-studied family of proteins known to exist from prokaryotes to higher eukaryotes [1]
A full ABC transporter consists of four distinct domains: two transmembrane domains (TMDs) consisting of six transmembrane helices (TMHs) and two nucleotide binding domains (NBD), located on the cytosolic side of the membrane [3]
To investigate putative ABC proteins, the HMM profile of the ABC transporter domain was utilized as the queries to search against 5213 protein coding ORFs in C. glabrata genome
Summary
ABC superfamily known as ‘Traffic ATPases’ is very diverse and well-studied family of proteins known to exist from prokaryotes to higher eukaryotes [1]. ABC proteins are promiscuous translocator of wide range of substrates such as sugars, amino acids, ions, peptides, cholesterol, metabolites, and toxins across the biological membranes, which are powered by ATP hydrolysis [2]. These proteins are known to perform diverse functions and their ability to confer MDR brought them to eminence. ABCA is known to exist in animal, plant and various protists but is absent in yeast genome [14]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
