Role of Streptococcus sanguinis sortase A in bacterial colonization

Yamaguchi, M.; Terao, Yutaka; Ogawa, Taiji; Takahashi, Toyomi; Hamada, Shigeyuki; Kawabata, Shigetada

doi:10.1016/j.micinf.2006.08.010

Cited by 76 publications

(66 citation statements)

References 26 publications

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“…Recent NMR analyses by Naik et al (38) revealed that the backbone dynamics of the ␤6/␤7 loop in SrtA change significantly upon calcium binding. 15 Engineering the Substrate Specificity of S. aureus SrtA used the NPQTN-containing peptide Abz-KVENPQTNAGTDap(DNP)-NH 2 . SrtB is less active than SrtA, and correspondingly greater concentrations of enzyme (94.8 M SrtB versus 1 M SrtA) and longer assay times (3 h versus 30 min) were required to obtain similar levels of product formation.…”

Section: Motifmentioning

confidence: 99%

“…In Streptococcus gordonii, srtA inactivation leads to decreased surface protein display, reduced fibronectin binding in vitro, and a reduced ability to colonize the oral mucosa of mice (10). Likewise, srtA knockouts from Streptococcus family members S. mutans (11), S. pneumonia (12), S. pyogenes (13), S. suis (14), S. sanguinis (15), and S. agalactiae (16) have been shown to have attenuated pathogenicity.…”

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confidence: 99%

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Engineering the Substrate Specificity of Staphylococcus aureus Sortase A

Bentley

Gaweska

Kielec

et al. 2007

Journal of Biological Chemistry

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The Staphylococcus aureus transpeptidase Sortase A (SrtA) anchors virulence and colonization-associated surface proteins to the cell wall. SrtA selectively recognizes a C-terminal LPXTG motif, whereas the related transpeptidase Sortase B (SrtB) recognizes a C-terminal NPQTN motif. In both enzymes, cleavage occurs after the conserved threonine, followed by amide bond formation between threonine and the pentaglycine cross-bridge of cell wall peptidoglycan. Genetic and biochemical studies strongly suggest that SrtA and SrtB exhibit exquisite specificity for their recognition motifs. To better understand the origins of substrate specificity within these two isoforms, we used sequence and structural analysis to predict residues and domains likely to be involved in conferring substrate specificity. Mutational analyses and domain swapping experiments were conducted to test their function in substrate recognition and specificity. Marked changes in the specificity profile of SrtA were obtained by replacing the ␤6/␤7 loop in SrtA with the corresponding domain from SrtB. The chimeric ␤6/␤7 loop swap enzyme (SrtLS) conferred the ability to acylate NPQTNcontaining substrates, with a k cat /K m app of 0.0062 ؎ 0.003 M ؊1 s ؊1 . This enzyme was unable to perform the transpeptidation stage of the reaction, suggesting that additional domains are required for transpeptidation to occur. The overall catalytic specificity profile (k cat /K m app (NPQTN)/k cat /K m app (LPETG)) of SrtLS was altered 700,000-fold from SrtA. These results indicate that the ␤6/␤7 loop is an important site for substrate recognition in sortases.

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Section: Motifmentioning

confidence: 99%

mentioning

confidence: 99%

Engineering the Substrate Specificity of Staphylococcus aureus Sortase A

Bentley

Gaweska

Kielec

et al. 2007

Journal of Biological Chemistry

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“…Bacterial association with and invasion into hBMECs or the human alveolar cell line A549 were quantified as previously described, with minor modifications [12,19,26,52]. hBMECs or A549 cells were seeded at 2 × 10 5 cells into 24-well plates 1 day prior to bacterial infection.…”

Section: Methodsmentioning

confidence: 99%

Competence-induced protein Ccs4 facilitates pneumococcal invasion into brain tissue and virulence in meningitis

et al. 2018

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Streptococcus pneumoniae is a major pathogen that causes pneumonia, sepsis, and meningitis. The candidate combox site 4 (ccs4) gene has been reported to be a pneumococcal competence-induced gene. Such genes are involved in development of S. pneumoniae competence and virulence, though the functions of ccs4 remain unknown. In the present study, the role of Ccs4 in the pathogenesis of pneumococcal meningitis was examined. We initially constructed a ccs4 deletion mutant and complement strains, then examined their association with and invasion into human brain microvascular endothelial cells. Wild-type and Ccs4-complemented strains exhibited significantly higher rates of association and invasion as compared to the ccs4 mutant strain. Deletion of ccs4 did not change bacterial growth activity or expression of NanA and CbpA, known brain endothelial pneumococcal adhesins. Next, mice were infected either intravenously or intranasally with pneumococcal strains. In the intranasal infection model, survival rates were comparable between wild-type strain-infected and ccs4 mutant strain-infected mice, while the ccs4 mutant strain exhibited a lower level of virulence in the intravenous infection model. In addition, at 24 hours after intravenous infection, the bacterial burden in blood was comparable between the wild-type and ccs4 mutant strain-infected mice, whereas the wild-type strain-infected mice showed a significantly higher bacterial burden in the brain. These results suggest that Ccs4 contributes to pneumococcal invasion of host brain tissues and functions as a virulence factor.

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“…SrtA homologs are responsible for anchoring the majority of LPXTG containing streptococcal surface proteins and have been identified in the genomes of S. pyogenes [110], S. gordonii [111], S. mutans [112], S. suis [94], S. pneumoniae [113], S. agalactiae [114], and S. sanguinis [115]. More than one sortase gene has been identified in S. pyogenes [110], S. pneumoniae [116] and S. suis [117].…”

Section: Covalently Bound Cell Wall Proteinsmentioning

confidence: 99%

Human pathogenic streptococcal proteomics and vaccine development

Cole

Henningham

Gillen

et al. 2008

Proteomics Clinical Apps

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Gram-positive streptococci are non-motile, chain-forming bacteria commonly found in the normal oral and bowel flora of warm-blooded animals. Over the past decade, a proteomic approach combining 2-DE and MS has been used to systematically map the cellular, surface-associated and secreted proteins of human pathogenic streptococcal species. The public availability of complete streptococcal genomic sequences and the amalgamation of proteomic, genomic and bioinformatic technologies have recently facilitated the identification of novel streptococcal vaccine candidate antigens and therapeutic agents. The objective of this review is to examine the constituents of the streptococcal cell wall and secreted proteome, the mechanisms of transport of surface and secreted proteins, and describe the current methodologies employed for the identification of novel surface-displayed proteins and potential vaccine antigens.

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Role of Streptococcus sanguinis sortase A in bacterial colonization

Cited by 76 publications

References 26 publications

Engineering the Substrate Specificity of Staphylococcus aureus Sortase A

Engineering the Substrate Specificity of Staphylococcus aureus Sortase A

Competence-induced protein Ccs4 facilitates pneumococcal invasion into brain tissue and virulence in meningitis

Human pathogenic streptococcal proteomics and vaccine development

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