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Identification and characterization of metal uptake ABC transporters in Mycobacterium tuberculosis unveil their ligand specificity.

Suraj Mandal,S. Nayak,S. Kanaujia

Published 2021 in International Journal of Biological Macromolecules

ABSTRACT

Mycobacterium tuberculosis, one of the major threats to mankind, requires micronutrients like metal ions for their survival and pathogenicity inside the host system. Intracellular pathogens such as M. tuberculosis have co-evolved to combat the nutritional immunity developed by the host. It has developed eminent mechanisms to sequester essential metal ions from the host system. One such prominent mechanism to scavenge metal ions to thrive in the host cell involves ATP-binding cassette (ABC) transporters, which transport metal ions (in free and/or complex forms) across the cell membrane. This study employs a high-throughput data mining analysis to identify open reading frames (ORFs) encoding metal uptake ABC transporters in M. tuberculosis H37Rv. In total, 19 ORFs resulting in seven ABC transport systems and two P-type ATPases were identified, which are potentially involved in the uptake of different metal ions. The results also suggest the existence of a subunit sharing mechanism in M. tuberculosis where the transmembrane and nucleotide binding domains are shared among different ABC transport systems indicating the import of multiple substrates via a single ABC transporter. Thus, this study reflects an overview of the repertoire of metal-specific ABC transport systems in M. tuberculosis H37Rv, providing potential therapeutic targets for the future.

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