Model for the Controlled Synthesis of O-Antigen Repeat Units Involving the WaaL Ligase

ABSTRACT The Wzx/Wzy O-antigen pathway involves synthesis of a repeat unit (O unit) consisting of 3 to 8 sugars on an inner-membrane-embedded lipid carrier. These O units are translocated across the membrane to its periplasmic face by Wzx, while retaining linkage to the carrier, and then polymerized...

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Main Authors: Yaoqin Hong, Peter R. Reeves
Format: Article
Language:English
Published: American Society for Microbiology 2016-02-01
Series:mSphere
Online Access:https://journals.asm.org/doi/10.1128/mSphere.00074-15
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author Yaoqin Hong
Peter R. Reeves
author_facet Yaoqin Hong
Peter R. Reeves
author_sort Yaoqin Hong
collection DOAJ
description ABSTRACT The Wzx/Wzy O-antigen pathway involves synthesis of a repeat unit (O unit) consisting of 3 to 8 sugars on an inner-membrane-embedded lipid carrier. These O units are translocated across the membrane to its periplasmic face by Wzx, while retaining linkage to the carrier, and then polymerized by Wzy to O-antigen polymer, which WaaL ligase transfers to a lipopolysaccharide precursor to complete lipopolysaccharide synthesis, concomitantly releasing the lipid carrier. This lipid carrier is also used for peptidoglycan assembly, and sequestration is known to be toxic. Thus, O-unit synthesis must involve precise regulation to meet demand but avoid overproduction. Here we show that loss of WaaL reverses a known growth defect in a Salmonella mutant that otherwise accumulates O-unit intermediates and propose that WaaL is also involved in a novel feedback mechanism to regulate O-unit synthesis, based on the availability of O units on the periplasmic face of the membrane.
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spelling doaj.art-2eb7142a319c4ec0834f4fff513cbe822022-12-21T19:51:53ZengAmerican Society for MicrobiologymSphere2379-50422016-02-011110.1128/mSphere.00074-15Model for the Controlled Synthesis of O-Antigen Repeat Units Involving the WaaL LigaseYaoqin Hong0Peter R. Reeves1School of Molecular Bioscience (D17), The University of Sydney, New South Wales, AustraliaSchool of Molecular Bioscience (D17), The University of Sydney, New South Wales, AustraliaABSTRACT The Wzx/Wzy O-antigen pathway involves synthesis of a repeat unit (O unit) consisting of 3 to 8 sugars on an inner-membrane-embedded lipid carrier. These O units are translocated across the membrane to its periplasmic face by Wzx, while retaining linkage to the carrier, and then polymerized by Wzy to O-antigen polymer, which WaaL ligase transfers to a lipopolysaccharide precursor to complete lipopolysaccharide synthesis, concomitantly releasing the lipid carrier. This lipid carrier is also used for peptidoglycan assembly, and sequestration is known to be toxic. Thus, O-unit synthesis must involve precise regulation to meet demand but avoid overproduction. Here we show that loss of WaaL reverses a known growth defect in a Salmonella mutant that otherwise accumulates O-unit intermediates and propose that WaaL is also involved in a novel feedback mechanism to regulate O-unit synthesis, based on the availability of O units on the periplasmic face of the membrane.https://journals.asm.org/doi/10.1128/mSphere.00074-15
spellingShingle Yaoqin Hong
Peter R. Reeves
Model for the Controlled Synthesis of O-Antigen Repeat Units Involving the WaaL Ligase
mSphere
title Model for the Controlled Synthesis of O-Antigen Repeat Units Involving the WaaL Ligase
title_full Model for the Controlled Synthesis of O-Antigen Repeat Units Involving the WaaL Ligase
title_fullStr Model for the Controlled Synthesis of O-Antigen Repeat Units Involving the WaaL Ligase
title_full_unstemmed Model for the Controlled Synthesis of O-Antigen Repeat Units Involving the WaaL Ligase
title_short Model for the Controlled Synthesis of O-Antigen Repeat Units Involving the WaaL Ligase
title_sort model for the controlled synthesis of o antigen repeat units involving the waal ligase
url https://journals.asm.org/doi/10.1128/mSphere.00074-15
work_keys_str_mv AT yaoqinhong modelforthecontrolledsynthesisofoantigenrepeatunitsinvolvingthewaalligase
AT peterrreeves modelforthecontrolledsynthesisofoantigenrepeatunitsinvolvingthewaalligase