Biogenesis and functions of bacterial S-layers

Fagan, Robert P.; Fairweather, Neil F.

doi:10.1038/nrmicro3213

Cited by 294 publications

(343 citation statements)

References 121 publications

(120 reference statements)

Supporting

Mentioning

341

Contrasting

Order By: Relevance

“…HMW SLP is responsible for binding to the cell wall and possesses three cell wall‐binding domains (pfam 04122, CWB2). There are 28 SlpA paralogues in the C. difficile genome, each of which possesses three CWB2 domains, and many also possess “functional” regions 5, 10, 11. Understanding the structure and function of the range of proteins within the S‐layer of C. difficile is of major importance if the S‐layer is to be exploited as a drug target.…”

Section: Introductionmentioning

confidence: 99%

The molecular structure of the glycoside hydrolase domain of Cwp19 from Clostridium difficile

et al. 2017

View full text Add to dashboard Cite

Clostridium difficile is a burden to healthcare systems around the world, causing tens of thousands of deaths annually. The S‐layer of the bacterium, a layer of protein found of the surface of cells, has received a significant amount of attention over the past two decades as a potential target to combat the growing threat presented by C. difficile infections. The S‐layer contains a wide range of proteins, each of which possesses three cell wall‐binding domains, while many also possess a “functional” region. Here, we present the high resolution structure of the functional region of one such protein, Cwp19 along with preliminary functional characterisation of the predicted glycoside hydrolase. Cwp19 has a TIM barrel fold and appears to possess a high degree of substrate selectivity. The protein also exhibits peptidoglycan hydrolase activity, an order of magnitude slower than that of lysozyme and is the first member of glycoside hydrolase‐like family 10 to be characterised. This research goes some way to understanding the role of Cwp19 in the S‐layer of C. difficile.DatabaseStructural data are available in the PDB under the accession numbers 5OQ2 and 5OQ3.

show abstract

Section: Introductionmentioning

confidence: 99%

The molecular structure of the glycoside hydrolase domain of Cwp19 from Clostridium difficile

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Two S-layer proteins of B. anthracis, Sap and EA1, are endowed with S-layer homology (SLH) domains, which retain these proteins in the bacterial envelope by binding to the secondary cell wall polysaccharide (SCWP) (13-15). S-layer protein crystallization domains, responsible for the spontaneous assembly of these polypeptides into a paracrystalline array (16), form a twodimensional lattice that can be thought of as bacterial integument (17)(18)(19).The structural genes of S-layer proteins, sap and eag, are flanked by genes encoding determinants for S-layer protein secretion (secA2 and slaP) (12) or pyruvylation (csaB) (14) as well as acetylation of the SCWP (patA1/2 and patB1/2) (20). CsaB-mediated pyruvylation of the terminal N-acetylmannosamine (ManNAc) of the SCWP (21), with the repeat struc- (22), is a prerequisite for the assembly of S-layer proteins and 22 B. anthracis S-layer-associated proteins (BSLs) (14).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

LytR-CpsA-Psr Enzymes as Determinants of Bacillus anthracis Secondary Cell Wall Polysaccharide Assembly

et al. 2014

View full text Add to dashboard Cite

bBacillus anthracis, the causative agent of anthrax, replicates as chains of vegetative cells by regulating the separation of septal peptidoglycan. Surface (S)-layer proteins and associated proteins (BSLs) function as chain length determinants and bind to the secondary cell wall polysaccharide (SCWP). In this study, we identified the B. anthracis lcpD mutant, which displays increased chain length and S-layer assembly defects due to diminished SCWP attachment to peptidoglycan. In contrast, the B. anthracis lcpB3 variant displayed reduced cell size and chain length, which could be attributed to increased deposition of BSLs. In other bacteria, LytR-CpsA-Psr (LCP) proteins attach wall teichoic acid (WTA) and polysaccharide capsule to peptidoglycan. B. anthracis does not synthesize these polymers, yet its genome encodes six LCP homologues, which, when expressed in S. aureus, promote WTA attachment. We propose a model whereby B. anthracis LCPs promote attachment of SCWP precursors to discrete locations in the peptidoglycan, enabling BSL assembly and regulated separation of septal peptidoglycan. Bacillus anthracis, the causative agent of anthrax, is a sporeforming, Gram-positive bacterium that germinates in host infected tissues and replicates as elongated chains of vegetative forms (1, 2). This unique growth pattern appears to be caused by the regulated separation of septal peptidoglycan, which generates bacterial chains whose mere size precludes clearance by host phagocytes (3-5). The genetic determinants for B. anthracis chain formation are conserved among pathogenic species of the Bacillus cereus group and, as demonstrated with B. cereus G9241, likely contribute to disease pathogenesis (6, 7). Hallmarks of pathogenic Bacillus species are virulence plasmids, pXO-1 and pXO-2 in B. anthracis (8, 9), providing for toxin production and capsulation (10, 11) as well as the chromosomally encoded surface (S)-layer locus (12). Two S-layer proteins of B. anthracis, Sap and EA1, are endowed with S-layer homology (SLH) domains, which retain these proteins in the bacterial envelope by binding to the secondary cell wall polysaccharide (SCWP) (13-15). S-layer protein crystallization domains, responsible for the spontaneous assembly of these polypeptides into a paracrystalline array (16), form a twodimensional lattice that can be thought of as bacterial integument (17)(18)(19).The structural genes of S-layer proteins, sap and eag, are flanked by genes encoding determinants for S-layer protein secretion (secA2 and slaP) (12) or pyruvylation (csaB) (14) as well as acetylation of the SCWP (patA1/2 and patB1/2) (20). CsaB-mediated pyruvylation of the terminal N-acetylmannosamine (ManNAc) of the SCWP (21), with the repeat struc- (22), is a prerequisite for the assembly of S-layer proteins and 22 B. anthracis S-layer-associated proteins (BSLs) (14). PatAB1/2-mediated acetylation of SCWP molecules affects the assembly of EA1 and of some but not all BSLs (20). Recent studies have begun to identify genes for SCWP synthesis, which, unlike py...

show abstract

“…Importantly, in Mycobacterium tuberculosis the disruption of the pathway responsible of adhesins mannosylation was found to strongly attenuate its virulence (21). The glycosylation of surface (S-) layer proteins which cover the cell surface of a variety of bacterial species is a common modification of this class of proteins (25,26). The extensive MS analysis performed in mutant backgrounds on the S-layer proteins of Geobacillus stearothermophilus and Paenibacillus alvei have made possible the reconstruction of the biosynthesis pathway for S-layer glycans, and also to propose a model for their export and transfer to S-layer proteins (27,28).…”

mentioning

confidence: 99%

O-Glycosylation of the N-terminal Region of the Serine-rich Adhesin Srr1 of Streptococcus agalactiae Explored by Mass Spectrometry

Chaze

Guillot

Valot³

et al. 2014

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Serine-rich (Srr) proteins exposed at the surface of Gram-positive bacteria are a family of adhesins that contribute to the virulence of pathogenic staphylococci and streptococci. Lectin-binding experiments have previously shown that Srr proteins are heavily glycosylated. We report here the first mass-spectrometry analysis of the glycosylation of Streptococcus agalactiae Srr1. After Srr1 enrichment and trypsin digestion, potential glycopeptides were identified in collision induced dissociation spectra using X! Tandem. The approach was then refined using higher energy collisional dissociation fragmentation which led to the simultaneous loss of sugar residues, production of diagnostic oxonium ions and backbone fragmentation for glycopeptides. This Protein glycosylation takes place in bacteria. A considerable amount of information on the biochemical pathways involved in protein glycosylation has been obtained in the genera Campylobacter and Neisseria (1-3). Hence, functional studies performed on Gram-negative bacteria have revealed important properties of protein glycosylation pathways. Like in eukaryotes, proteins can be glycosylated on asparagines (N-glycosylation) or serine/threonine residues (O-glycosylation). Two modes of glycan transfer onto proteins have been characterized in Gram-negative bacteria. In the first, the activated glycan is synthesized on a lipid carrier on the cytoplasmic side of the membrane. After membrane translocation, the glycan portion of the polyprenyl-phosphate-glycan intermediate is transferred en bloc to the protein by an oligosaccharyltransferase active in the periplasm. Such mechanism has been demonstrated for N-glycosylation in Campylobacter jejuni (4 -6) and O-glycosylation in Neisseria gonorrheae (7-9). These pathways are responsible for the glycosylation of more than 65 proteins in C. jejuni (10) and 12 different proteins in N.

show abstract

Biogenesis and functions of bacterial S-layers

Cited by 294 publications

References 121 publications

The molecular structure of the glycoside hydrolase domain of Cwp19 from Clostridium difficile

The molecular structure of the glycoside hydrolase domain of Cwp19 from Clostridium difficile

LytR-CpsA-Psr Enzymes as Determinants of Bacillus anthracis Secondary Cell Wall Polysaccharide Assembly

O-Glycosylation of the N-terminal Region of the Serine-rich Adhesin Srr1 of Streptococcus agalactiae Explored by Mass Spectrometry

Contact Info

Product

Resources

About