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

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, Staphylococcus aureus causes a diverse spectrum of severe infections in humans, including bacteremia, endocarditis, and osteomyelitis, as well as skin and soft tissue infections. Notorious for decades as a major source of nosocomial infections, S. aureus has recently taken on a new role in causing an escalating number of community-acquired infections. To offset the problems of antibiotic-resistant S. aureus strains, preventive measures (e.g., immunization) should be explored as a complement to existing therapeutic approaches aimed at controlling this bacterial pathogen.Humans are a reservoir for S. aureus, and the nose is the principal site of staphylococcal colonization. Approximately 20% of people persistently carry S. aureus in the anterior nares, ϳ60% are intermittent carriers, and ϳ20% are noncarriers (19). Nasal carriage is a known risk factor for staphylococcal infection in a number of clinical settings (51). Certain patient populations that show higher rates of S. aureus nasal colonization have an increased risk of staphylococcal infection. These populations include patients with diabetes, eczema, and human immunodeficiency virus infection, individuals receiving continuous ambulatory peritoneal dialysis or hemodialysis, and injection drug users (19). Moreover, patients in hospitals or individuals living in crowded conditions often show higherthan-normal rates of S. aureus nasal colonization. The source of ϳ80% of S. aureus bacteremias is endogenous since infecting bacteria have been shown by genotypic analysis to be identical to organisms recovered from the nasal mucosa (48, 53). These observations support an approach in which systemic S. aureus infections are prevented by eliminating or reducing nasal carriage.One approach commonly used to reduce S. aureus carriage in individuals at risk for staphylococcal infection involves topical treatment with a nasal ointment containing the antibiotic mupirocin. Eradication of nasal carriage with topical mupirocin has been correlated with a reduction in the incidence of S. aureus infection in some patient populations (20, 45), but not in others (40,54). Whereas mupirocin is effective in decolonizing nasal carriers, recolonization often occurs from extranasal carriage sites (52). Of further concern is the emergence of mupirocin resistance in S. aureus (31, 46). The utility of

Resolution of Staphylococcus aureus Biofilm Infection Using Vaccination and Antibiotic Treatment

“…However, while injection of plasmid containing clfA increased clearance in a mastitis model, protection was not generated against infection in an intraperitoneal challenge (6). Immunization with rClfB led to lessened colonization of murine nares by S. aureus (33). Vaccination with IsdB led to increased survival rates of 20 to 40% in a murine sepsis model (18).…”

Protection from the acquisition of Staphylococcus aureus nasal carriage by cross-reactive antibody to a pneumococcal dehydrogenase

“…Passive i.p. immunization with a monoclonal antibody against clumping factor B resulted in reduced nasal carriage of S. aureus in mice (36), indicating that systemic antibody can protect against S. aureus colonization regardless of Spa. Our study provides another example of antibody-dependent inhibition of nasal carriage of a Spa-sufficient strain, suggesting that the immune-evasive effect ascribed to Spa may be of limited importance during colonization.…”

“…A Spa mutant often is used in vitro, especially whenever secondary antibody-detection methods are used. It has been assumed that the effect(s) of antibody in vivo would be negated similarly by Spa, but antibody-mediated protection has been demonstrated against nasal colonization with Spa-sufficient strains (31,36). Passive i.p.…”

Antibodies toStaphylococcus aureuscapsular polysaccharides 5 and 8 perform similarlyin vitrobut are functionally distinctin vivo

“…Female Swiss Webster mice (7 to 8 week old; Charles River Laboratories) were injected intravenously with 100 mg mAbs 4C2 (CP5-specific) or 5A6 (CP8-specific) or an irrelevant IgG1 mAb control. 64 For certain experiments, mice were injected similarly with 0.3 to 1 mg polyclonal CP5-Epa, CP8-Epa, or Shigella 2a-Epa rabbit IgG, purified by a Protein A affinity chromatography, as described. 25 After 24 h the mice were challenged IP with a 500 ml S. aureus inoculum.…”