Dataset Information

Structure and mechanism of Staphylococcus aureus TarM, the wall teichoic acid ?-glycosyltransferase.

ABSTRACT: Unique to Gram-positive bacteria, wall teichoic acids are anionic glycopolymers cross-stitched to a thick layer of peptidoglycan. The polyol phosphate subunits of these glycopolymers are decorated with GlcNAc sugars that are involved in phage binding, genetic exchange, host antibody response, resistance, and virulence. The search for the enzymes responsible for GlcNAcylation in Staphylococcus aureus has recently identified TarM and TarS with respective ?- and ?-(1-4) glycosyltransferase activities. The stereochemistry of the GlcNAc attachment is important in balancing biological processes, such that the interplay of TarM and TarS is likely important for bacterial pathogenicity and survival. Here we present the crystal structure of TarM in an unusual ternary-like complex consisting of a polymeric acceptor substrate analog, UDP from a hydrolyzed donor, and an ?-glyceryl-GlcNAc product formed in situ. These structures support an internal nucleophilic substitution-like mechanism, lend new mechanistic insight into the glycosylation of glycopolymers, and reveal a trimerization domain with a likely role in acceptor substrate scaffolding.

SUBMITTER: Sobhanifar S

PROVIDER: S-EPMC4330757 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Structure and mechanism of Staphylococcus aureus TarM, the wall teichoic acid α-glycosyltransferase.

Sobhanifar Solmaz S Worrall Liam James LJ Gruninger Robert J RJ Wasney Gregory A GA Blaukopf Markus M Baumann Lars L Lameignere Emilie E Solomonson Matthew M Brown Eric D ED Withers Stephen G SG Strynadka Natalie C J NC

Proceedings of the National Academy of Sciences of the United States of America 20150126 6

Unique to Gram-positive bacteria, wall teichoic acids are anionic glycopolymers cross-stitched to a thick layer of peptidoglycan. The polyol phosphate subunits of these glycopolymers are decorated with GlcNAc sugars that are involved in phage binding, genetic exchange, host antibody response, resistance, and virulence. The search for the enzymes responsible for GlcNAcylation in Staphylococcus aureus has recently identified TarM and TarS with respective α- and β-(1-4) glycosyltransferase activiti ...[more]

PMID: 25624472

Similar Datasets

Project description:Staphylococcus aureus (S. aureus) constantly evolves under host and environment pressures. The monitoring network is essential in assessing the epidemiology of S. aureus infections. A total of 555 S. aureus isolates were collected from five hospitals in three different geographical regions of China for the investigation of molecular characteristics, antibiotic resistance, virulence gene, and wall teichoic acid (WTA) glycosyltransferase gene profiles. 233 (42.0%) isolates were identified as MRSA, and 323 (58.2%) were defined as multidrug-resistant (MDR) isolates. MRSA prevalence showed no significant difference among the three regions. In contrast, the MDR prevalence was significantly higher in central China than that in northern China (63.5% vs. 50.8%, P < 0.05). Thirty-eight sequence types (STs) belonging to 17 clone complexes (CCs) and 126 distinct spa-types were identified. The most prevalent clone was ST59-t437 (9.7%, 54/555), followed by ST22-t309 (7.6%, 42/555) and ST5-t2460 (7.2%, 40/555). Most ST59-t437 and ST5-t2460 were MRSA isolates, whereas most ST22-t309 was MSSA isolates. The predominant clones varied in different geographical areas. The distribution of the pvl, etb, tsst, clfb, sdrC, sdrD, hlg, fnbA, and hla genes showed significant differences among different regions. We found five WTA glycosyltransferase gene profiles, with tarP-/tarS+/tarM-/tagN- being the most common combination. Remarkably, the tarP gene was identified in more CCs than just CC5 and CC398. All of 16 tarP-positive isolates also contained the tarS. Moreover, tarS was present in almost all S. aureus isolates except 10 ST630 isolates. The tagN gene was only detected in 10 of 12 ST630 S. aureus isolates without tarS. The tarM gene was absent in CC5 and CC398. In brief, there were regional differences among molecular characteristics, antibiotic resistance, and virulence gene profiles. The tarS-negative ST630 lineage carried the tagN, which was never found before, indicating that it may be capable of expressing GroP-α-GalNAc WTA and exchanging mobile genetic elements with coagulase-negative staphylococci (CoNS).

Project description:ABSTRACT The major clonal lineages of the human pathogen Staphylococcus aureus produce cell wall-anchored anionic poly-ribitol-phosphate (RboP) wall teichoic acids (WTA) substituted with d-Alanine and N-acetyl-d-glucosamine. The phylogenetically isolated S. aureus ST395 lineage has recently been found to produce a unique poly-glycerol-phosphate (GroP) WTA glycosylated with N-acetyl-d-galactosamine (GalNAc). ST395 clones bear putative WTA biosynthesis genes on a novel genetic element probably acquired from coagulase-negative staphylococci (CoNS). We elucidated the ST395 WTA biosynthesis pathway and identified three novel WTA biosynthetic genes, including those encoding an ?-O-GalNAc transferase TagN, a nucleotide sugar epimerase TagV probably required for generation of the activated sugar donor substrate for TagN, and an unusually short GroP WTA polymerase TagF. By using a panel of mutants derived from ST395, the GalNAc residues carried by GroP WTA were found to be required for infection by the ST395-specific bacteriophage ?187 and to play a crucial role in horizontal gene transfer of S. aureus pathogenicity islands (SaPIs). Notably, ectopic expression of ST395 WTA biosynthesis genes rendered normal S. aureus susceptible to ?187 and enabled ?187-mediated SaPI transfer from ST395 to regular S. aureus. We provide evidence that exchange of WTA genes and their combination in variable, mosaic-like gene clusters have shaped the evolution of staphylococci and their capacities to undergo horizontal gene transfer events. IMPORTANCE The structural highly diverse wall teichoic acids (WTA) are cell wall-anchored glycopolymers produced by most Gram-positive bacteria. While most of the dominant Staphylococcus aureus lineages produce poly-ribitol-phosphate WTA, the recently described ST395 lineage produces a distinct poly-glycerol-phosphate WTA type resembling the WTA backbone of coagulase-negative staphylococci (CoNS). Here, we analyzed the ST395 WTA biosynthesis pathway and found new types of WTA biosynthesis genes along with an evolutionary link between ST395 and CoNS, from which the ST395 WTA genes probably originate. The elucidation of ST395 WTA biosynthesis will help to understand how Gram-positive bacteria produce highly variable WTA types and elucidate functional consequences of WTA variation.

Dataset Information

Structure and mechanism of Staphylococcus aureus TarM, the wall teichoic acid ?-glycosyltransferase.

Publications

Structure and mechanism of Staphylococcus aureus TarM, the wall teichoic acid α-glycosyltransferase.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets