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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F21%3A00554945" target="_blank" >RIV/60077344:_____/21:00554945 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.pnas.org/doi/full/10.1073/pnas.2023663118" target="_blank" >https://www.pnas.org/doi/full/10.1073/pnas.2023663118</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1073/pnas.2023663118" target="_blank" >10.1073/pnas.2023663118</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

<a href="/cs/project/LM2018129" target="_blank" >LM2018129: Národní infrastruktura pro biologické a medicínské zobrazování Czech-BioImaging</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Proceedings of the National Academy of Sciences of the United States of America

ISSN

0027-8424

e-ISSN

—

Svazek periodika

118

Číslo periodika v rámci svazku

17

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

e2023663118

Kód UT WoS článku

000648438500019

EID výsledku v databázi Scopus

2-s2.0-85105348097