Expression of staphylococcal clumping factor A impedes macrophage phagocytosis

Palmqvist, Niklas; Patti, Joseph M.; Tarkowski, Andrzej; Josefsson, Elisabet

doi:10.1016/j.micinf.2003.11.005

Cited by 56 publications

(31 citation statements)

References 23 publications

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“…Earlier work had implicated SD repeat proteins as important determinants of pathogenesis, and they coat S. aureus with fibrinogen and fibrin and provide for bacterial escape from innate host defenses (41,42). The important contributions of ClfA are readily apparent in a mouse model for S. aureus bloodstream infection.…”

Section: Discussionmentioning

confidence: 99%

N-Acetylglucosaminylation of Serine-Aspartate Repeat Proteins Promotes Staphylococcus aureus Bloodstream Infection

Thomer

Becker

Emolo

et al. 2014

Journal of Biological Chemistry

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Background: Staphylococcus aureus agglutinates in plasma in a manner that requires host fibrinogen and clumping factor A, a bacterial surface protein with serine-aspartate (SD) repeats. Results: SdgB modifies serine residues in SD repeats with GlcNAc, and this glycosylation contributes to the pathogenesis of sepsis. Conclusion: Glycosylation of SD repeats aids bacterial escape from host defenses. Significance: Interference with glycosylation may alter staphylococcal infections.

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Section: Discussionmentioning

confidence: 99%

N-Acetylglucosaminylation of Serine-Aspartate Repeat Proteins Promotes Staphylococcus aureus Bloodstream Infection

Thomer

Becker

Emolo

et al. 2014

Journal of Biological Chemistry

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“…It has been shown that ClfA is involved in the pathogenesis of experimental endocarditis (Moreillon et al 1995;Entenza et al 2000). ClfA is also involved in causing arthritis in mice (Josefsson et al 2001), and impedes phagocytosis of S. aureus by macrophages (Palmqvist et al 2004). Both ClfA and ClfB bind and activate platelets, through fibrinogen-dependent and fibrinogen-independent pathways, which may have an impact on the pathogenesis of invasive disease (O'Brien et al 2002a).…”

Section: Factors Involved In Adhesion To Host Cellsmentioning

confidence: 99%

Infection control of Staphylococcus aureus : spa typing to elucidate transmission

Mernelius¹

2015

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Staphylococcus aureus is a commensal of the human flora, primarily colonizing the anterior nares and throat, but it may also cause infections ranging from mild skin and soft tissue infections to severe diseases such as endocarditis and septicemia. S. aureus is also a major nosocomial problem increasing with the worldwide dissemination of methicillin-resistant S. aureus (MRSA).The main vector for bacterial cross-transmission in healthcare settings is the hands of healthcare workers (HCWs). No S. aureus was detected in the air in this thesis demonstrating that transmission through air is not important. Despite the fact that good compliance with hand hygiene is essential to prevent cross-transmission the compliance is generally less than 50 %.Gold standard to track bacterial transmission in healthcare settings has for long been pulsedfield gel electrophoresis (PFGE), a method that is labor-intensive, lacks consensus protocol and relies on semi-subjective analysis. Molecular typing by sequencing of the hypervariable part of the S. aureus protein A gene (spa typing) has overcome these problems and has shown promising results in epidemiological investigations.The aims of this thesis were to study bacterial transmission with S. aureus colonization of newborn infants as a model and to evaluate spa typing as a molecular tool. Additionally, the influence of compliance with hygiene guidelines on S. aureus transmission was assessed.Analysis of 280 MRSA isolates by spa typing revealed excellent typeability and epidemiological concordance and satisfactory discriminatory power. Additionally, spa typing was considered superior to PFGE thanks to its accessibility, ease of use and rapidity. Also, spa typing results are registered in a global database, facilitating inter-laboratory comparison.The prevalence of S. aureus ranged from 41 % to 66 % in the populations studied and males had the highest colonization rate. Throat was the premier colonization site for adults and transmission from individuals colonized in the throat only was documented, suggesting that throat cultures should be included in S. aureus screening programs. The umbilicus was the premier colonization site for newborn infants. Incubating the swabs in enrichment broth prior to plating increased the prevalence of S. aureus positive samples by 46 %, resulting in prevalence viii ranging from 51 % to 70 % in the populations studied. Thus enrichment prior to plating is necessary to determine more truthful S. aureus colonization rates. There were no indications of an institutional flora, as the colonization rates, spa type distribution and antibiotic resistance prevalence were similar among parents and HCWs.Direct observations and self-reporting by HCWs were both validated as tools for monitoring compliance with hygiene guidelines. The compliance with hygiene guidelines was significantly higher following a 10-point hygiene intervention as compared to baseline. The compliance was also higher three years after the intervention in three of four participating departm...

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“…Based on their ability to bind fibrinogen on the S. aureus cell wall, they inhibit deposition of or access to opsonins to the pathogen (20). ClfA has been shown to impede macrophage phagocytosis (31) and to bind and activate the complement regulator factor I, thereby inactivating C3b, the central complement component (15). Other S. aureus surface proteins involved in host immune evasion are protein A (SpA) and IsdH (40).…”

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confidence: 99%

SpA, ClfA, and FnbA Genetic Variations Lead to Staphaurex Test-Negative Phenotypes in Bovine Mastitis Staphylococcus aureus Isolates

2011

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Staphylococcus aureus encodes many proteins that act as virulence factors, leading to a variety of diseases, including mastitis in cows. Among these virulence factors, SpA, ClfA, ClfB, FnbA, and FnbB are important for the ability of S. aureus to adhere to and invade host cells as well as to evade host immune responses. The interaction between these S. aureus surface proteins and human immunoglobulin G and fibrinogen that are coupled to latex particles is utilized to induce latex agglutination reactions, which are used widely in diagnostic kits for confirmation of presumptive S. aureus isolates. In this study, the Staphaurex latex agglutination test was performed on a collection of confirmed bovine mastitis S. aureus isolates. Notably, 54% (43/79 isolates) of these isolates exhibited latex agglutination-negative phenotypes (Staphaurex-negative result). To gain insights into the reasons for the high frequency of Staphaurex-negative bovine mastitis S. aureus isolates, the spa, clfA, clfB, fnbA, and fnbB genes were examined. Specific genetic changes in spa, clfA, and fnbA, as well as a loss of fnbB, which may impair SpA, ClfA, FnbA, and FnbB functions in latex agglutination reactions, were detected in Staphaurex-negative S. aureus isolates. The genetic changes included a premature stop codon in the spa gene, leading to a truncated SpA protein that is unable to participate in S. aureus cell-mediated agglutination of latex particles. In addition, clfA and fnbA genetic polymorphisms were detected that were linked to ClfA and FnbA amino acid changes that may significantly reduce fibrinogen-binding activity. The genetic variations in these S. aureus isolates might also have implications for their bovine mastitis virulence capacity.

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Expression of staphylococcal clumping factor A impedes macrophage phagocytosis

Cited by 56 publications

References 23 publications

N-Acetylglucosaminylation of Serine-Aspartate Repeat Proteins Promotes Staphylococcus aureus Bloodstream Infection

N-Acetylglucosaminylation of Serine-Aspartate Repeat Proteins Promotes Staphylococcus aureus Bloodstream Infection

Infection control of Staphylococcus aureus : spa typing to elucidate transmission

SpA, ClfA, and FnbA Genetic Variations Lead to Staphaurex Test-Negative Phenotypes in Bovine Mastitis Staphylococcus aureus Isolates

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