Protection against Experimental<i>Staphylococcus aureus</i>Arthritis by Vaccination with Clumping Factor A, a Novel Virulence Determinant

Josefsson, Elisabet; Hartford, Orla; O’Brien, Louise; Patti, Joseph M.; Foster, Timothy J.

doi:10.1086/324430

Cited by 255 publications

(210 citation statements)

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“…Some of these proteins were recognized by sera from infected patients and were also found to be associated with clinically invasive disease but their functions remain to be elucidated. One or more of these proteins could be suitable for development as vaccine candidates, alongside the current contenders ClfA (Josefsson et al, 2001) and Cna (Nilsson et al, 1998;Visai et al, 2000). …”

Section: Discussionmentioning

confidence: 99%

Characterization of novel LPXTG-containing proteins of Staphylococcus aureus identified from genome sequences

et al. 2003

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Section: Discussionmentioning

confidence: 99%

Characterization of novel LPXTG-containing proteins of Staphylococcus aureus identified from genome sequences

et al. 2003

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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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“…However, the traditional vaccine available for mastitis (Chang et al, 2008;Middleton, 2008) is rather ineffective due to the fact that animal is lack of immune response to new infections (Reid and Szymanski, 2010). It has been suggested that vaccine produced from the combinations of antigens including CPs and adhensins would be an effective way against bovine mastitis caused by S. aureus (Lorena et al, 2008;Josefsson et al, 2001), but little information is available in this area.…”

Section: Introductionmentioning

confidence: 99%

ASSESSMENT OF IMMUNOGENICITY OF CP8, CLFA-FnBPB AND CP8-CLFA-FnBPB ANTIGENS

Liu

Hao

Wang

et al. 2013

American Journal of Animal and Veterinary Sciences

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To assess the effects of conjugating Capsular Polysaccharide (CP) with Clumping factor A (ClfA) and Fibronectin-Binding Proteins B (FnBPB) on the immunogenicity of the antigen, CP was isolated and purified from serotype 8 (CP8) Staphylococcus aureus from bovine mastitis dairy herds in Inner Mongolia and ClfA-FnBPB was produced with Escherichia coli encoding a fusion protein ClfA-FnBPB gene. The CP8-ClfA-FnBPB complete antigen was constructed by first attaching Alcohol Dehydrogenase (ADH) to CP8 which was then combined with ClfA-FnBPB at the presence of EDC (1-ethyl-3, (3-dimethylaminopropyl carbodiimide). The immunogenicity of CP8, ClfA-FnBPB and CP8-ClfA-FnBPB was determined by intraperitoneal injecting 40 8-wk old of Balb/c mice four groups with 0.2 ml/mouse of 0.9% NaCl (Control) or CP8, ClfA-FnBPB and CP8-ClfA-FnBPB solution. The mice were group-fed with same pellet diet in an environmentally controlled room with a constant temperature of 22°C and 12h/24h light. The concentration of CP8, ClfA-FnBPB or CP-ClfA-FnBPB in respective solutions was 50, 25 or 75 µg mL −1 . Two injections were given, on d7 and d21 of the experiment. Blood samples were taken on d0, d14, d21 and d28 and measured for the antibodies titer. On d28, all mice were injected with CP8 type of S. aureus and the mortality of the mice determined for the following 14 days (challenge test). The results showed that ClfA-FnBPB was successfully expressed by E coli and the isolated and purified ClfA-FnBPB was successfully conjugated with CP8 to yield a CP8-ClfA-FnBPB complete antigen. Mice immunized with CP8-ClfA-FnBPB had higher antibody titer than that of CP8 (p<0.01) and ClfA-FnBPB (p<0.05) groups. Antibody titer in mice immunized with ClfA-FnBPB antigen was also higher (p<0.05) than that of CP8 and 0.9% NaCl groups. Survival rate of the mice at the end of 2-wk challenge test for Control, CP8, ClfA-FnBPB and CP8-ClfAFnBPB groups were 20 30, 60 and 80% respectively. These results demonstrated that conjugating CP8 with ClfA-FnBPB to form CP8-ClfA-FnBPB complete antigen significantly increased immunogenicity of the antigen and markedly enhanced the survival rate of the mice infected with the bacteria. The information suggests that vaccine based on the CP8-ClfA-FnBPB antigen would be more effective in controlling bovine mastitis than those based on CP8 and ClfA-FnBPB alone, but further animal study is needed.

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Protection against ExperimentalStaphylococcus aureusArthritis by Vaccination with Clumping Factor A, a Novel Virulence Determinant

Cited by 255 publications

References 29 publications

Characterization of novel LPXTG-containing proteins of Staphylococcus aureus identified from genome sequences

Characterization of novel LPXTG-containing proteins of Staphylococcus aureus identified from genome sequences

Infection control of Staphylococcus aureus : spa typing to elucidate transmission

ASSESSMENT OF IMMUNOGENICITY OF CP8, CLFA-FnBPB AND CP8-CLFA-FnBPB ANTIGENS

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