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.
... Anthrax 79 -- In Eukaryotic Cells, Genetic Information Is Contained in Multiple Chromosomes 80 -- Synthesis ... ... Aspects of Bacterial Growth 98 Cell Multiplication Requires a Source of Energy and Raw Material for Synthesis ... ... Critical Thinking Questions 109 Further Reading 109 -- 5 Metabolism: The Generation of Energy and Synthesis ... ... Critical Thinking Questions 131 Further Reading 131 -- 6 Informational Macromolecules: -- Function, Synthesis ... ... by a Substance Resembling the Enzyme’s Normal Substrate 653 -- Some Antibiotics Impair Cell Wall Synthesis ...
XXVIII, 812 s. : il. ; 32 cm
