An ABC transporter Wzm-Wzt catalyzes translocation of lipid-linked galactan across the plasma membrane in mycobacteria

0554945 - BC 2022 RIV US eng J - Journal Article
Savková, K. - Huszár, S. - Baráth, P. - Pakanová, Z. - Kozmon, S. - Vancová, Marie - Tesařová, Martina - Blasko, J. - Kalinak, M. - Singh, V. - Korduláková, J. - Mikušová, K.
An ABC transporter Wzm-Wzt catalyzes translocation of lipid-linked galactan across the plasma membrane in mycobacteria.
Proceedings of the National Academy of Sciences of the United States of America. Roč. 118, č. 17 (2021), č. článku e2023663118. ISSN 0027-8424. E-ISSN 1091-6490
R&D Projects: GA MŠMT(CZ) LM2018129
Institutional support: RVO:60077344
Keywords : lipopolysaccharide o-antigens * cell-wall * klebsiella-pneumoniae * escherichia-coli * linkage region * chain-length * biosynthesis * arabinogalactan * tuberculosis * lipoarabinomannan * mycobacterium * cell wall * transport * galactan
OECD category: Cell biology
Impact factor: 12.779, year: 2021
Method of publishing: Open access
https://www.pnas.org/doi/full/10.1073/pnas.2023663118

Mycobacterium tuberculosis, one of the deadliest pathogens in human history, is distinguished by a unique, multilayered cell wall, which offers the bacterium a high level of protection from the attacks of the host immune system. The primary structure of the cell wall core, composed of covalently linked peptidoglycan, branched heteropolysaccharide arabinogalactan, and mycolic acids, is well known, and numerous enzymes involved in the biosynthesis of its components are characterized. The cell wall biogenesis takes place at both cytoplasmic and periplasmic faces of the plasma membrane, and only recently some of the specific transport systems translocating the metabolic intermediates between these two compartments have been characterized [M. Jackson, C. M. Stevens, L. Zhang, H. I. Zgurskaya, M. Niederweis, Chem. Rev., 10.1021/acs.chemrev.0c00869 (2020)]. In this work, we use CRISPR interference methodology in Mycobacterium smegmatis to functionally characterize an ATP binding cassette (ABC) transporter involved in the translocation of galactan precursors across the plasma membrane. We show that genetic knockdown of the transmembrane subunit of the transporter results in severe morphological changes and the accumulation of an aberrantly long galactan precursor. Based on similarities with structures and functions of specific O-antigen ABC transporters of gram-negative bacteria [C. Whitfield, D. M. Williams, S. D. Kelly, J. Biol. Chem. 295, 10593-10609 (2020)], we propose a model for coupled synthesis and export of the galactan polymer precursor in mycobacteria.
Permanent Link: http://hdl.handle.net/11104/0329558