Transcriptional regulation of the Staphylococcus aureus collagen adhesion gene, cna

Gillaspy, Allison F.; Patti, Joseph M.; Smeltzer, Mark S.

doi:10.1128/iai.65.4.1536-1540.1997

Cited by 27 publications

(32 citation statements)

References 28 publications

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“…A second murein hydrolase, probably LytM, is activated in the sar mutant and sar±agr double mutant to a greater extent than in the parental strain or the single agr mutant. A similar pattern of regulation was demonstrated for the expression of the collagen-binding protein, which is inhibited by sar but unaffected by agr (Gillaspy et al, 1997;Blevins et al, 1999). In our study, we could demonstrate that fnbA expression was strongly inhibited by agr but activated by sar and that sar is also required for fnbA expression in an agr-negative background.…”

Section: Discussionsupporting

confidence: 86%

Agr‐independent regulation of fibronectin‐binding protein(s) by the regulatory locus sar in Staphylococcus aureus

Wolz

Pöhlmann-Dietze

Steinhuber

et al. 2000

Molecular Microbiology

117

115

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Fibronectin‐binding proteins (FnBPs) are thought to be important for the attachment of Staphylococcus aureus during infection. The regulation of the genes fnbA and fnbB by the global regulatory loci sar and agr was examined using site‐specific regulatory mutants of S. aureus strain Newman. The results from binding assays using both aqueous and solid‐phase fibronectin as well as ligand blotting with biotinylated fibronectin showed that the expression of FnBPA is enhanced in the agr mutant but inhibited in the sar mutant and the sar–agr double mutant. The same regulatory pattern was observed in Northern blot analysis using fnbA‐specific probes. The introduction of sar on a multicopy plasmid increased the already enhanced fnbA transcription of the agr mutant. FnBPB was not detectable by ligand blotting and the fnbB promoter activity in promoter fusion assays was not affected by either sar or agr. The sequence encompassing ORF3 located upstream of sarA was found to be essential for the activation of fnbA transcription. We hypothesize that this sequence may modulate SarA expression and/or activity on the post‐transcriptional level. Gel shift assays demonstrated that SarA binds to the fnbA promoter fragments, probably as a dimer. DNase I footprinting assays with SarA revealed a protected area of 102 bp upstream of fnbA.

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Section: Discussionsupporting

confidence: 86%

Agr‐independent regulation of fibronectin‐binding protein(s) by the regulatory locus sar in Staphylococcus aureus

Wolz

Pöhlmann-Dietze

Steinhuber

et al. 2000

Molecular Microbiology

117

115

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“…This lack of reactivity is somewhat surprising since we were able to detect the collagen adhesin on the surface of S. aureus strain Phillips, immunohistochemically using antibodies to M55 (results not shown). Moreover, Gillaspy et al (24) for M17 [n ϭ 14]; 0.03Ϯ0.00 for B1 [n ϭ 14]; and 0.01Ϯ0.00 for OVA [n ϭ 14]). 14 d after inoculation with S. aureus Phillips there were no significant differences with respect to serum IL-6 levels between mice immunized with M55 or BSA (1,768Ϯ258 versus 2,225Ϯ641, NS).…”

Section: Resultsmentioning

confidence: 99%

Vaccination with a recombinant fragment of collagen adhesin provides protection against Staphylococcus aureus-mediated septic death.

Im¹,

Patti²,

Bremell³

et al. 1998

J. Clin. Invest.

Self Cite

158

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Staphylococcus aureus is a major cause of nosocomial and community-acquired infections. Morbidity and mortality due to infections such as sepsis, osteomyelitis, septic arthritis, and invasive endocarditis remain high despite the use of antibiotics. The emergence of antibiotic resistant super bugs mandates that alternative strategies for the prevention and treatment of S. aureus infections are developed. We investigated the ability of vaccination with a recombinant fragment of the S. aureus collagen adhesin to protect mice against sepsis-induced death. Actively immunized NMRI mice were intravenously inoculated with the S. aureus clinical isolate strain Phillips. 14 d after inoculation, mortality in the collagen adhesin-vaccinated group was only 13%, compared with 87% in the control antigen immunized group (P < 0.001). To determine if the protective effect was antibody mediated, we passively immunized naive mice with collagen adhesin-specific antibodies. Similar to the active immunization strategy, passive transfer of collagen adhesin-specific antibodies protected mice against sepsis-induced death. In vitro experiments indicated that S. aureus opsonized with sera from collagen adhesin immunized mice promoted phagocytic uptake and enhanced intracellular killing compared with bacteria opsonized with sera from control animals. These results indicate that the collagen adhesin is a viable target in the development of immunotherapeutics against S. aureus.

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“…The regulation of surface proteins in S. aureus is widely believed to be under the control of the agr virulence regulon, which induces the expression of surface proteins during growth at low cell density (384,591,665). However, a recent study of the collagen adhesion protein suggests that it is under the control of another, overlapping regulatory system, sar (262).…”

Section: Staphylococcimentioning

confidence: 99%

Surface Proteins of Gram-Positive Bacteria and Mechanisms of Their Targeting to the Cell Wall Envelope

Navarre

Schneewind

1999

Microbiol Mol Biol Rev

1,185

601

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SUMMARY The cell wall envelope of gram-positive bacteria is a macromolecular, exoskeletal organelle that is assembled and turned over at designated sites. The cell wall also functions as a surface organelle that allows gram-positive pathogens to interact with their environment, in particular the tissues of the infected host. All of these functions require that surface proteins and enzymes be properly targeted to the cell wall envelope. Two basic mechanisms, cell wall sorting and targeting, have been identified. Cell well sorting is the covalent attachment of surface proteins to the peptidoglycan via a C-terminal sorting signal that contains a consensus LPXTG sequence. More than 100 proteins that possess cell wall-sorting signals, including the M proteins of Streptococcus pyogenes, protein A of Staphylococcus aureus, and several internalins of Listeria monocytogenes, have been identified. Cell wall targeting involves the noncovalent attachment of proteins to the cell surface via specialized binding domains. Several of these wall-binding domains appear to interact with secondary wall polymers that are associated with the peptidoglycan, for example teichoic acids and polysaccharides. Proteins that are targeted to the cell surface include muralytic enzymes such as autolysins, lysostaphin, and phage lytic enzymes. Other examples for targeted proteins are the surface S-layer proteins of bacilli and clostridia, as well as virulence factors required for the pathogenesis of L. monocytogenes (internalin B) and Streptococcus pneumoniae (PspA) infections. In this review we describe the mechanisms for both sorting and targeting of proteins to the envelope of gram-positive bacteria and review the functions of known surface proteins.

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Transcriptional regulation of the Staphylococcus aureus collagen adhesion gene, cna

Cited by 27 publications

References 28 publications

Agr‐independent regulation of fibronectin‐binding protein(s) by the regulatory locus sar in Staphylococcus aureus

Agr‐independent regulation of fibronectin‐binding protein(s) by the regulatory locus sar in Staphylococcus aureus

Vaccination with a recombinant fragment of collagen adhesin provides protection against Staphylococcus aureus-mediated septic death.

Surface Proteins of Gram-Positive Bacteria and Mechanisms of Their Targeting to the Cell Wall Envelope

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