<i>Staphylococcus aureus</i>
            Sortase, an Enzyme that Anchors Surface Proteins to the Cell Wall

Mazmanian, Sarkis K.; Liu, Gwen; Ton‐That, Hung; Schneewind, Olaf

doi:10.1126/science.285.5428.760

Cited by 950 publications

(845 citation statements)

References 18 publications

Supporting

Mentioning

829

Contrasting

Unclassified

Order By: Relevance

“…Strains containing mutations in the genes encoding sortase A, alpha-hemolysin, protein A, and the global virulence regulators SarA and AgrA exhibit attenuated virulence in mouse models of pneumonia (12,18,47). Sortase A catalyzes the anchoring of proteins, including protein A, into the cell wall peptidoglycan (30). Gomez et al showed that protein A binds to TNFR1 to induce airway inflammatory responses during S. aureus infection (12).…”

mentioning

confidence: 99%

Host Airway Proteins Interact withStaphylococcus aureusduring Early Pneumonia

et al. 2008

View full text Add to dashboard Cite

Staphylococcus aureus is a major cause of hospital-acquired pneumonia and is emerging as an important etiological agent of community-acquired pneumonia. Little is known about the specific host-pathogen interactions that occur when S. aureus first enters the airway. A shotgun proteomics approach was utilized to identify the airway proteins associated with S. aureus during the first 6 h of infection. Host proteins eluted from bacteria recovered from the airways of mice 30 min or 6 h following intranasal inoculation under anesthesia were subjected to liquid chromatography and tandem mass spectrometry. A total of 513 host proteins were associated with S. aureus 30 min and/or 6 h postinoculation. A majority of the identified proteins were host cytosolic proteins, suggesting that S. aureus was rapidly internalized by phagocytes in the airway and that significant host cell lysis occurred during early infection. In addition, extracellular matrix and secreted proteins, including fibronectin, antimicrobial peptides, and complement components, were associated with S. aureus at both time points. The interaction of 12 host proteins shown to bind to S. aureus in vitro was demonstrated in vivo for the first time. The association of hemoglobin, which is thought to be the primary staphylococcal iron source during infection, with S. aureus in the airway was validated by immunoblotting. Thus, we used our recently developed S. aureus pneumonia model and shotgun proteomics to validate previous in vitro findings and to identify nearly 500 other proteins that interact with S. aureus in vivo. The data presented here provide novel insights into the host-pathogen interactions that occur when S. aureus enters the airway.

show abstract

mentioning

confidence: 99%

Host Airway Proteins Interact withStaphylococcus aureusduring Early Pneumonia

et al. 2008

View full text Add to dashboard Cite

show abstract

“…5). To date, there are other examples of machinery that combine two proteins/peptides such as ubiquitin ligase found in the ubiquitin-proteasome complex 27 , sortase 28 , which participates in peptidoglycan biosynthesis, and intein, which is active in protein splicing 29 . However, PGM1 uses a completely distinct mechanism from these enzymes, and thus defines a new type of machinery.…”

Section: Discussionmentioning

confidence: 99%

A peptide ligase and the ribosome cooperate to synthesize the peptide pheganomycin

et al. 2014

View full text Add to dashboard Cite

Peptide antibiotics are typically biosynthesized by one of two distinct machineries in a ribosome-dependent or -independent manner. Pheganomycin (PGM) (1) and related analogues consist of the nonproteinogenic amino acid (S)-2-(3,5-dihydroxy-4-hydroxymethyl)phenyl-2-guanidinoacetic acid (2) and a proteinogenic core peptide, making their origin uncertain. We report the identification of the biosynthetic gene cluster from Streptomyces cirratus responsible for PGM production. Surprisingly, the cluster contains a gene encoding multiple precursor peptides along with several genes plausibly encoding enzymes for the synthesis of amino acid 2. We identified pgm1, which has an ATP-grasp domain, as potentially capable of linking the precursor peptides with 2, and validate this hypothesis using deletion mutants and in vitro reconstitution. We document PGM1's substrate permissivity, which could be rationalized by a large binding pocket as confirmed via structural and mutagenesis experiments. This is the first example of cooperative peptide synthesis achieved by ribosomes and peptide ligases using a peptide nucleophile.2

show abstract

“…Interestingly, the predicted amino acid sequence of orf365 shares significant homology with a sortase identified from S. oureus. The sortase is involved in cleaving the conserved anchor consensus, LPXTG, between threonine and glycine as well as in anchoring the cleaved fragment to the peptidoglycan cell wall (Mazmanian et al, 1999). A mutation in or365 leaves monomeric FimA, which possesses the anchor domain, unassembled.…”

Section: Oto 1998) Andmentioning

confidence: 99%

Molecular Strategies for Fimbrial Expression and Assembly

Fives-Taylor

2001

Critical Reviews in Oral Biology & Medicine

View full text Add to dashboard Cite

Fimbriae or pili are long, filamentous, multimeric macromolecules found on the bacterial cell surface. Bacteria express a diverse array of fimbriae or pili that are involved in bacterial adherence and invasion. Fimbriae can be categorized based on their modes of expression and assembly. Type 1 fimbriae and P pili are distributed peritrichously and translocated to the cell surface by a chaperone/usher pathway. Type 4 pili are located at the pole of the cell and assembled via the type 11 secretion system. Curli fimbriae are coiled surface structures assembled by an extracellular nucleation/precipitation pathway. Fimbriae of oral Gram-negative and Gram-positive bacteria have not been well-studied as compared with the fimbriae of enteric pathogens. Oral pathogens, such as Eikenella corrodens, Actinobacillus actinomycetemcomitans, and Porphyromonas gingivalis, possess fimbriae that have been implicated in bacterial adhesion and invasion. These fimbriae are potential virulence factors in oral infectious processes. A. actinomycetemcomitans and E. corrodens have Type 4-like fimbriae, whereas P. gingivalis displays a unique type of fimbriae. To date, fimbriae of the oral primary colonizers, Actinomyces naeslundii and Streptococcus parasanguis, represent the only fimbriae characterized for any Gram-positive bacteria. The putative major fimbrial subunits, FimA and FimP of A. naeslundii and FapI of S. parasanguis, contain a signal sequence and cell-wall-sorting signal. The presence of extensive dipeptide repeats in FapI makes it unique among fimbrial molecules. Based on experimental data, a nucleation/precipitation pathway is proposed for fimbrial biogenesis of both S. parasanguis and A. naeslundii, although we cannot rule out an alternative covalent linkage model. The model systems described in this review served as a framework for hypotheses for how the known molecular factors of fimbriae on oral bacteria may be expressed and assembled.

show abstract

Staphylococcus aureus Sortase, an Enzyme that Anchors Surface Proteins to the Cell Wall

Cited by 950 publications

References 18 publications

Host Airway Proteins Interact withStaphylococcus aureusduring Early Pneumonia

Host Airway Proteins Interact withStaphylococcus aureusduring Early Pneumonia

A peptide ligase and the ribosome cooperate to synthesize the peptide pheganomycin

Molecular Strategies for Fimbrial Expression and Assembly

Contact Info

Product

Resources

About