Comparison of carbohydrate ABC importers from Mycobacterium tuberculosis

Author(s)

De la Torre, I, Lilia ; Vergara Meza, Jose G. ^{[1, 2]} ; Cabarca, Sindy ^{[3, 4, 2]} ; Costa-Martins, Andre G. ^[5] ; Balan, Andrea ^{[3, 4, 6]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo - Brazil

^[2] De la Torre, Lilia, I, Univ Sucre, Biomed Res Grp, Sucre - Colombia

^[3] De la Torre, Lilia, I, Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil

^[4] De la Torre, Lilia, I, Univ Estadual Campinas, Inst Biol, Genect & Mol Biol Postgrad Program, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Lab Appl Struct Biol, Av Prof Lineu Prestes 1374, Sao Paulo - Brazil

• Document type: Journal article
• Source: BMC Genomics; v. 22, n. 1 NOV 19 2021.
• Web of Science Citations: 0

Abstract

Background Mycobacterium tuberculosis, the etiological agent of tuberculosis, has at least four ATP-Binding Cassette (ABC) transporters dedicated to carbohydrate uptake: LpqY/SugABC, UspABC, Rv2038c-41c, and UgpAEBC. LpqY/SugABC transporter is essential for M. tuberculosis survival in vivo and potentially involved in the recycling of cell wall components. The three-dimensional structures of substrate-binding proteins (SBPs) LpqY, UspC, and UgpB were described, however, questions about how these proteins interact with the cognate transporter are still being explored. Components of these transporters, such as SBPs, show high immunogenicity and could be used for the development of diagnostic and therapeutic tools. In this work, we used a phylogenetic and structural bioinformatics approach to compare the four systems, in an attempt to predict functionally important regions. Results Through the analysis of the putative orthologs of the carbohydrate ABC importers in species of Mycobacterium genus it was shown that Rv2038c-41c and UgpAEBC systems are restricted to pathogenic species. We showed that the components of the four ABC importers are phylogenetically separated into four groups defined by structural differences in regions that modulate the functional activity or the interaction with domain partners. The regulatory region in nucleotide-binding domains, the periplasmic interface in transmembrane domains and the ligand-binding pocket of the substrate-binding proteins define their substrates and segregation in different branches. The interface between transmembrane domains and nucleotide-binding domains show conservation of residues and charge. Conclusions The presence of four ABC transporters in M. tuberculosis dedicated to uptake and transport of different carbohydrate sources, and the exclusivity of at least two of them being present only in pathogenic species of Mycobacterium genus, highlights their relevance in virulence and pathogenesis. The significant differences in the SBPs, not present in eukaryotes, and in the regulatory region of NBDs can be explored for the development of inhibitory drugs targeting the bacillus. The possible promiscuity of NBDs also contributes to a less specific and more comprehensive control approach. (AU)

• FAPESP's process: 18/20162-9 - Investigating the Pathogenesis and Drug Resistance in Microorganisms - Characterization and Control of ATP-Binding Cassette Transporters
• Grantee: Andrea Balan Fernandes
• Support Opportunities: Regular Research Grants