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Substrate recognition and catalysis by LytB, a pneumococcal peptidoglycan hydrolase involved in virulence

Lookup NU author(s): Palma Rico Lastres, Christine Aldridge, Professor Waldemar Vollmer

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

Streptococcus pneumoniae is a major cause of life-threatening diseases worldwide. Here we provide an in-depth functional characterization of LytB, the peptidoglycan hydrolase responsible for physical separation of daughter cells. Identified herein as an N-acetylglucosaminidase, LytB is involved also in colonization and invasion of the nasopharynx, biofilm formation and evasion of host immunity as previously demonstrated. We have shown that LytB cleaves the GlcNAc-beta-(1,4)-MurNAc glycosidic bond of peptidoglycan building units. The hydrolysis occurs at sites with fully acetylated GlcNAc moieties, with preference for uncross-linked muropeptides. The necessity of GlcN acetylation and the presence of a single acidic moiety (Glu585) essential for catalysis strongly suggest a substrate-assisted mechanism with anchimeric assistance of the acetamido group of GlcNAc moieties. Additionally, modelling of the catalytic region bound to a hexasaccharide tripentapeptide provided insights into substrate-binding subsites and peptidoglycan recognition. Besides, cell-wall digestion products and solubilisation rates might indicate a tight control of LytB activity to prevent unrestrained breakdown of the cell wall. Choline-independent localization at the poles of the cell, mediated by the choline-binding domain, peptidoglycan modification, and choline-mediated (lipo) teichoic-acid attachment contribute to the high selectivity of LytB. Moreover, so far unknown chitin hydrolase and glycosyltransferase activities were detected using GlcNAc oligomers as substrate.

Publication metadata

Author(s): Rico-Lastres P, Diez-Martinez R, Iglesias-Bexiga M, Bustamante N, Aldridge C, Hesek D, Lee M, Mobashery S, Gray J, Vollmer W, Garcia P, Menendez M

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2015

Volume: 5

Online publication date: 05/11/2015

Acceptance date: 12/10/2015

Date deposited: 03/03/2016

ISSN (electronic): 2045-2322

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/srep16198

DOI: 10.1038/srep16198

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