scholarly journals Immunization with Staphylococcus aureus Clumping Factor B, a Major Determinant in Nasal Carriage, Reduces Nasal Colonization in a Murine Model

2006 ◽  
Vol 74 (4) ◽  
pp. 2145-2153 ◽  
Author(s):  
Adam C. Schaffer ◽  
Robert M. Solinga ◽  
Jordan Cocchiaro ◽  
Marta Portoles ◽  
Kevin B. Kiser ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Vaccine Development ◽  
Passive Immunization ◽  
Nasal Carriage ◽  
Staphylococcal Infection ◽  
Nasal Colonization ◽  
Accessory Gene ◽  
Factor B ◽  
Wide Range ◽  
Clumping Factor B

ABSTRACT Staphylococcus aureus is responsible for a wide range of infections, including soft tissue infections and potentially fatal bacteremias. The primary niche for S. aureus in humans is the nares, and nasal carriage is a documented risk factor for staphylococcal infection. Previous studies with rodent models of nasal colonization have implicated capsule and teichoic acid as staphylococcal surface factors that promote colonization. In this study, a mouse model of nasal colonization was utilized to demonstrate that S. aureus mutants that lack clumping factor A, collagen binding protein, fibronectin binding proteins A and B, polysaccharide intercellular adhesin, or the accessory gene regulator colonized as well as wild-type strains colonized. In contrast, mutants deficient in sortase A or clumping factor B (ClfB) showed reduced nasal colonization. Mice immunized intranasally with killed S. aureus cells showed reduced nasal colonization compared with control animals. Likewise, mice that were immunized systemically or intranasally with a recombinant vaccine composed of domain A of ClfB exhibited lower levels of colonization than control animals exhibited. A ClfB monoclonal antibody (MAb) inhibited S. aureus binding to mouse cytokeratin 10. Passive immunization of mice with this MAb resulted in reduced nasal colonization compared with the colonization observed after immunization with an isotype-matched control antibody. The mouse immunization studies demonstrate that ClfB is an attractive component for inclusion in a vaccine to reduce S. aureus nasal colonization in humans, which in turn may diminish the risk of staphylococcal infection. As targets for vaccine development and antimicrobial intervention are assessed, rodent nasal colonization models may be invaluable.

scholarly journals Key Role for Clumping Factor B in Staphylococcus aureus Nasal Colonization of Humans

PLoS Medicine ◽  
2008 ◽  
Vol 5 (1) ◽  
pp. e17 ◽  
Author(s):  
Heiman F. L Wertheim ◽  
Evelyn Walsh ◽  
Roos Choudhurry ◽  
Damian C Melles ◽  
Hélène A. M Boelens ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Nasal Colonization ◽  
Factor B ◽  
Clumping Factor B

scholarly journals Amoxicillin-Clavulanate Therapy Increases Childhood Nasal Colonization by Methicillin-Susceptible Staphylococcus aureus Strains Producing High Levels of Penicillinase

2004 ◽  
Vol 48 (12) ◽  
pp. 4618-4623 ◽  
Author(s):  
Didier Guillemot ◽  
Stephane Bonacorsi ◽  
John S. Blanchard ◽  
Philippe Weber ◽  
Sylvie Simon ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Drug Use ◽  
Odds Ratio ◽  
Selection Process ◽  
Nasal Carriage ◽  
Penicillin G ◽  
Nasal Colonization ◽  
Factors Associated ◽  
Amoxicillin Clavulanate ◽  
Resistant Strains

ABSTRACT We examined factors associated with penicillinase production by nasal carriage Staphylococcus aureus strains in 648 children aged 3 to 6 years attending 20 randomly sampled playschools. The children were prospectively monitored for drug use and medical events for 6 months and were then screened for S. aureus carriage. Isolates were tested for their susceptibility to penicillin G and methicillin, and penicillinase production by methicillin-susceptible, penicillin-resistant strains was quantified. S. aureus was isolated from 166 children (25.6%). Exposure to amoxicillin-clavulanate during the previous 3 months was associated with higher penicillinase production by penicillin-resistant, methicillin-susceptible strains (odds ratio, 3.6; P = 0.03). These results suggest that use of the amoxicillin-clavulanate combination could induce a herd selection process of S. aureus strains producing higher levels of penicillinase.

scholarly journals Nasal Colonisation by Staphylococcus aureus Depends upon Clumping Factor B Binding to the Squamous Epithelial Cell Envelope Protein Loricrin

2012 ◽  
Vol 8 (12) ◽  
pp. e1003092 ◽  
Author(s):  
Michelle E. Mulcahy ◽  
Joan A. Geoghegan ◽  
Ian R. Monk ◽  
Kate M. O'Keeffe ◽  
Evelyn J. Walsh ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Epithelial Cell ◽  
Envelope Protein ◽  
Cell Envelope ◽  
Factor B ◽  
Squamous Epithelial Cell ◽  
Clumping Factor B

scholarly journals Staphylococcus aureus clumping factor B mediates biofilm formation in the absence of calcium

Microbiology ◽  
2012 ◽  
Vol 158 (6) ◽  
pp. 1504-1512 ◽  
Author(s):  
Nabil M. Abraham ◽  
Kimberly K. Jefferson
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Factor B ◽  
Clumping Factor B

scholarly journals Force-Induced Strengthening of the Interaction between Staphylococcus aureus Clumping Factor B and Loricrin

mBio ◽  
2017 ◽  
Vol 8 (6) ◽  
Author(s):  
Pauline Vitry ◽  
Claire Valotteau ◽  
Cécile Feuillie ◽  
Simon Bernard ◽  
David Alsteens ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Epithelial Cell ◽  
Envelope Protein ◽  
Cell Envelope ◽  
Surface Protein ◽  
Binding Mechanism ◽  
Factor B ◽  
Squamous Epithelial Cell ◽  
High Affinity ◽  
Clumping Factor B

ABSTRACT Bacterial pathogens that colonize host surfaces are subjected to physical stresses such as fluid flow and cell surface contacts. How bacteria respond to such mechanical cues is an important yet poorly understood issue. Staphylococcus aureus uses a repertoire of surface proteins to resist shear stress during the colonization of host tissues, but whether their adhesive functions can be modulated by physical forces is not known. Here, we show that the interaction of S. aureus clumping factor B (ClfB) with the squamous epithelial cell envelope protein loricrin is enhanced by mechanical force. We find that ClfB mediates S. aureus adhesion to loricrin through weak and strong molecular interactions both in a laboratory strain and in a clinical isolate. Strong forces (~1,500 pN), among the strongest measured for a receptor-ligand bond, are consistent with a high-affinity “dock, lock, and latch” binding mechanism involving dynamic conformational changes in the adhesin. Notably, we demonstrate that the strength of the ClfB-loricrin bond increases as mechanical force is applied. These findings favor a two-state model whereby bacterial adhesion to loricrin is enhanced through force-induced conformational changes in the ClfB molecule, from a weakly binding folded state to a strongly binding extended state. This force-sensitive mechanism may provide S. aureus with a means to finely tune its adhesive properties during the colonization of host surfaces, helping cells to attach firmly under high shear stress and to detach and spread under low shear stress. IMPORTANCE Staphylococcus aureus colonizes the human skin and the nose and can cause various disorders, including superficial skin lesions and invasive infections. During nasal colonization, the S. aureus surface protein clumping factor B (ClfB) binds to the squamous epithelial cell envelope protein loricrin, but the molecular interactions involved are poorly understood. Here, we unravel the molecular mechanism guiding the ClfB-loricrin interaction. We show that the ClfB-loricrin bond is remarkably strong, consistent with a high-affinity “dock, lock, and latch” binding mechanism. We discover that the ClfB-loricrin interaction is enhanced under tensile loading, thus providing evidence that the function of an S. aureus surface protein can be activated by physical stress. IMPORTANCE Staphylococcus aureus colonizes the human skin and the nose and can cause various disorders, including superficial skin lesions and invasive infections. During nasal colonization, the S. aureus surface protein clumping factor B (ClfB) binds to the squamous epithelial cell envelope protein loricrin, but the molecular interactions involved are poorly understood. Here, we unravel the molecular mechanism guiding the ClfB-loricrin interaction. We show that the ClfB-loricrin bond is remarkably strong, consistent with a high-affinity “dock, lock, and latch” binding mechanism. We discover that the ClfB-loricrin interaction is enhanced under tensile loading, thus providing evidence that the function of an S. aureus surface protein can be activated by physical stress.

scholarly journals Development and Characterization of aStaphylococcus aureus Nasal Colonization Model in Mice

1999 ◽  
Vol 67 (10) ◽  
pp. 5001-5006 ◽  
Author(s):  
Kevin B. Kiser ◽  
Jean M. Cantey-Kiser ◽  
Jean C. Lee
Keyword(s):  
Vaccine Development ◽  
Nasal Carriage ◽  
Risk Groups ◽  
Hospital Environment ◽  
Nasal Colonization ◽  
Defective Mutant ◽  
Colonization Model ◽  
Antimicrobial Intervention

ABSTRACT Staphylococcus aureus nasal carriage is a risk factor for infection in humans, particularly in the hospital environment. Attenuation of carriage has proven effective in reducing the prevalence of infection in some high-risk groups. To study staphylococcal factors that influence nasal colonization, a mouse model of S. aureus nasal colonization was developed. Mice were inoculated intranasally with S. aureus Reynolds, and nasal carriage was evaluated by quantitating cultures of the nasal tissues from mice sacrificed at various time points after inoculation. The majority of mice inoculated with 108 CFU of S. aureusmaintained nasal carriage for at least 20 days. Nasal colonization rates were similar for inbred (BALB/c and C57BL/6) and outbred (ICR) mice. Colonization was not affected by mouse passage of strain Reynolds. Lower inoculum doses (<107 CFU) resulted in reduced colonization after 7 days. However, mice given streptomycin in their drinking water developed long-term carriage of S. aureus, and they were colonized with inocula as low as 105 CFU. Nasal colonization was also established with two other S. aureus strains (one strain each of human and murine origins). S. aureus recovered from the nares of experimentally colonized mice expressed high levels of capsule, and the ability of a capsule-defective mutant to persist in the nares was reduced in comparison to that of the parent strain. This nasal colonization model should prove useful for studies of factors that mediate S. aureus colonization and for assessment of targets for antimicrobial intervention or vaccine development.

scholarly journals Methicillin-Resistant Staphylococcus aureus Nasal Carriage among Janitors Working in Hospital and Non-Hospital Areas: A Comparative Cross-Sectional Study

2020 ◽  
Author(s):  
Seid Abie ◽  
Moges Tiruneh ◽  
Wondwossen Abebe
Keyword(s):  
Staphylococcus Aureus ◽  
Associated Factors ◽  
Nasal Carriage ◽  
Cross Sectional Study ◽  
Diffusion Method ◽  
Nasal Colonization ◽  
Sectional Study ◽  
Cross Sectional ◽  
Methicillin Resistant ◽  
Study Participants

Abstract Background: Nasal colonization of Methicillin-resistant Staphylococcus aureus (MRSA) plays a key role in the epidemiology and pathogenesis of both healthcare-associated and community-acquired MRSA infections in various populations. Screening of MRSA nasal colonization is important in the prevention and control of infection and may provide useful information to guide antimicrobial therapy. This study aimed to determine nasal carriage of MRSA, its antimicrobial susceptibility pattern, and associated factors among janitors working in hospital & non-hospital areas at the University of Gondar, Northwest Ethiopia.Methods: A comparative cross-sectional study was carried out in a total of 436 study participants (221 hospital and 215 non-hospital janitors) from January to May 2019. The study participants were sampled using a simple random sampling technique. Data on socio-demographic characteristics and associated factors were collected through face to face interviews using a structured questionnaire. Nasal swabs were collected and inoculated into Mannitol salt agar. MRSA was detected using cefoxitin (30µg) disc and an antibiotic susceptibility test was done using the disc diffusion method. Data were entered and analyzed using SPSS version 20 statistical package. P-value ≤ 0.05 was considered as statistically significant.Results: The overall prevalence of S. aureus was 101/436 (23.2%, [95% CI: 19.3-27.8], of which, 29.4% (65/221) were isolated from hospital and 16.7% (36/215) non-hospital janitors. The prevalence of MRSA was 4.8% (21/436) [95% CI: 3.0-6.9]; of these, 8.1% (18/221) of the isolates were from the hospital and 1.4% (3/215) non-hospital janitors, while MSSA in hospital & non-hospital janitors were 49 (22.2%) and 31 (14.4%), respectively. Among the MRSA isolates, 52.4% (11/21) were multi-drug resistant. Of these, 42.9% (9/18) were isolated from hospital and 66.7% (2/3) non-hospital janitors. Hence, nasal carriage of MRSA was significantly associated with hospitalization within the preceding year (AOR = 3.15, CI = 1.13-8.71).Conclusion: The present study revealed that high MSSA and MRSA were isolated from the hospital as compared to non-hospital janitors and high rates of antibiotics resistance were recorded in the hospital janitors. Consequently, hospitalizations were significantly associated with MRSA. Accordingly, regular screening of carriers in apparently healthy janitors is required for the prevention of nosocomial infections.

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