Staphylococcus aureus collagen adhesin contributes to the pathogenesis of osteomyelitis

Elasri, Mohamed O.; Thomas, J. R.; Skinner, Robert A.; Blevins, Jon S.; Beenken, Karen E.; Nelson, Carl L.; Smelter, M.S

doi:10.1016/s8756-3282(01)00632-9

Cited by 146 publications

(108 citation statements)

References 22 publications

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“…This observation raises the intriguing possibility that collagen type I, which is predominantly found in the synovia and bones, may be targeted. A similar association between Cna expression and collagen type I-binding S. aureus strains with arthritis or osteomyelitis has been proposed (22,24,26). The hypothesis that specific MSCRAMM surface molecules that target type I collagen, like Cpa in S. pyogenes or Cna in S. aureus, may provide only a subset of these pathogens with a niche-specific advantage for infection of the skeletal system merits consideration and further study.…”

Section: Discussionsupporting

confidence: 65%

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Streptococcus pyogenes Collagen Type I-binding Cpa Surface Protein

Kreikemeyer¹,

Nakata

Oehmcke

et al. 2005

Journal of Biological Chemistry

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The Streptococcus pyogenes collagen type I-binding protein Cpa (collagen-binding protein of group A streptococci) expressed by 28 serotypes of group A streptococci has been extensively characterized at the gene and protein levels. Evidence for three distinct families of cpa genes was found, all of which shared a common sequence encoding a 60-amino acid domain that accounted for selective binding to type I collagen. Surface plasmon resonance-based affinity measurements and functional studies indicated that the expression of Cpa was consistent with an attachment role for bacteria to tissue containing collagen type I. A cpa mutant displayed a significantly decreased internalization rate when incubated with HEp-2 cells but had no effect on the host cell viability. By utilizing serum from patients with a positive titer for streptolysin/DNase antibody, an increased anti-Cpa antibody titer was noted for patients with a clinical history of arthritis or osteomyelitis. Taken together, these results suggest Cpa may be a relevant matrix adhesin contributing to the pathogenesis of S. pyogenes infection of bones and joints.

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Section: Discussionsupporting

confidence: 65%

“…cartilage (10). The results from several animal infection models suggest that Cnaexpressing S. aureus strains can induce and promote septic arthritis, endocarditis, keratitis, and osteomyelitis (22)(23)(24)(25)(26). Recently, a Cna homologue was detected in the animal pathogen Streptococcus equi (27).…”

Section: Streptococcus Pyogenes (Group a Streptococci (Gas)mentioning

confidence: 99%

Streptococcus pyogenes Collagen Type I-binding Cpa Surface Protein

Kreikemeyer¹,

Nakata

Oehmcke

et al. 2005

Journal of Biological Chemistry

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“…4 To date, much of our knowledge of the pathogenesis of OM comes from animal models, 5 which have existed in chicken, 6 rat, 7,8 guinea pig, 9 rabbit, 10 dog, 11 sheep, 12 goat, 13 and most recently mouse. 14 While these models have been used to confirm the importance of bacterial adhesions identified from in vitro assays, [15][16][17] none of them contain quantitative endpoints that can determine bacterial load or growth in vivo. Thus, they are of limited value for assessing drug effects, bacterial mutants, and the role of host factors during the establishment of chronic OM.…”

Section: Introductionmentioning

confidence: 99%

Quantitative mouse model of implant‐associated osteomyelitis and the kinetics of microbial growth, osteolysis, and humoral immunity

Gromov

Søballe

et al. 2007

Journal Orthopaedic Research

138

164

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Although osteomyelitis (OM) remains a serious problem in orthopedics, progress has been limited by the absence of an in vivo model that can quantify the bacterial load, metabolic activity of the bacteria over time, immunity, and osteolysis. To overcome these obstacles, we developed a murine model of implant-associated OM in which a stainless steel pin is coated with Staphylococcus aureus and implanted transcortically through the tibial metaphysis. X-ray and micro-CT demonstrated concomitant osteolysis and reactive bone formation, which was evident by day 7. Histology confirmed all the hallmarks of implant-associated OM, namely: osteolysis, sequestrum formation, and involucrum of Gram-positive bacteria inside a biofilm within necrotic bone. Serology revealed that mice mount a protective humoral response that commences with an IgM response after 1 week, and converts to a specific IgG2b response against specific S. aureus proteins by day 11 postinfection. Real-time quantitative PCR (RTQ-PCR) for the S. aureus specific nuc gene determined that the peak bacterial load occurs 11 days postinfection. This coincidence of decreasing bacterial load with the generation of specific antibodies is suggestive of protective humoral immunity. Longitudinal in vivo bioluminescent imaging (BLI) of luxA-E transformed S. aureus (Xen29) combined with nuc RTQ-PCR demonstrated the exponential growth phase of the bacteria immediately following infection that peaks on day 4, and is followed by the biofilm growth phase at a significantly lower metabolic rate (p < 0.05). Collectively, these studies demonstrate the first quantitative model of implant-associated OM that defines the kinetics of microbial growth, osteolysis, and humoral immunity following infection. ß

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“…The importance of the MSCRAMM proteins to the virulence of S. aureus has been demonstrated by studying isogenic mutants in animal models of infection. The collagen-binding protein, Cna, was implicated in the pathogenesis of osteomyelitis and septic arthritis (1,6,7), and the fibrinogen-binding protein, ClfA, promoted experimental endocarditis (8) and septic arthritis (9).…”

mentioning

confidence: 99%

The N-terminal A Domain of Fibronectin-binding Proteins A and B Promotes Adhesion of Staphylococcus aureus to Elastin

Roche

Downer

Keane

et al. 2004

Journal of Biological Chemistry

122

117

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The ability of Staphylococcus aureus to adhere to components of the extracellular matrix is an important mechanism for colonization of host tissues during infection. We have previously shown that S. aureus binds elastin, a major component of the extracellular matrix. The integral membrane protein, elastin-binding protein (EbpS), binds soluble elastin peptides and tropoelastin via its surface-exposed N-terminal domain. In this study, we demonstrate that some strains of S. aureus adhere strongly to immobilized human elastin and that this interaction is independent of EbpS but instead is mediated by the fibronectin-binding proteins, FnBPA and FnBPB. Our results show that EbpS mutant cells adhere to elastin-coated plates, whereas the cells negative for FnBPA and FnBPB do not adhere to the plates. Furthermore, only wild-type cells from the exponential phase of growth adhered when FnBPs were expressed maximally. We show that adherence to elastin promoted by FnBPA was not affected by soluble fibronectin, suggesting that the elastin binding domain is distinct from the fibronectin binding regions. Recombinant FnBPA 37-544 (rFnBPA 37-544 ) protein corresponding to the A region of FnBPA and anti-FnBPA 37-544 antibodies inhibited FnBPA-mediated bacterial adherence to immobilized elastin. Finally, recombinant A domain proteins, rFnBPA 37-544 and rFnBPB 37-540 , bound immobilized elastin dose-dependently and saturably. This interaction was inhibited by soluble elastin peptides, suggesting a specific receptor-ligand interaction.

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Staphylococcus aureus collagen adhesin contributes to the pathogenesis of osteomyelitis

Cited by 146 publications

References 22 publications

Streptococcus pyogenes Collagen Type I-binding Cpa Surface Protein

Streptococcus pyogenes Collagen Type I-binding Cpa Surface Protein

Quantitative mouse model of implant‐associated osteomyelitis and the kinetics of microbial growth, osteolysis, and humoral immunity

The N-terminal A Domain of Fibronectin-binding Proteins A and B Promotes Adhesion of Staphylococcus aureus to Elastin

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