The Collagen-Binding Adhesin Is a Virulence Factor in Staphylococcus aureus Keratitis

Abstract

A collagen-binding strain of Staphylococcus aureus produced suppurative inflammation in a rabbit model of soft contact lens-associated bacterial keratitis more often than its collagen-binding-negative isogenic mutant. Reintroduction of the cna gene on a multicopy plasmid into the mutant helped it regain its corneal adherence and infectivity. The topical application of a collagen-binding peptide before bacterial challenge decreased S. aureus adherence to deepithelialized corneas. These data suggest that the collagen-binding adhesin is involved in the pathogenesis of S. aureus infection of the cornea.Our understanding of the pathogenesis of infectious diseases of the eye is emerging. The intact ocular surface thwarts most microorganisms, but predisposing factors such as contact lens wear can expose tissue components conducive to bacterial adhesion. A breakdown in local defenses and a source of microbial contaminants increase the risk of eye infection.Staphylococcus aureus is responsible for many types of human ocular infections (21) and accounts for 10% of culturepositive microbial keratitis at our institution. S. aureus adheres to the injured cornea (12) and releases proteins that disrupt corneal tissue (11).S. aureus possesses a family of adhesins that are localized at the microbial surface and that interact with extracellular matrix components such as collagen, fibronectin, fibrinogen, laminin, and elastin with high affinity and specificity (4, 13). One staphylococcal adhesin is composed of an N-terminal domain with a collagen-binding site and an antipodal domain that attaches to the bacterial cell wall and projects into the cytoplasm (16). We sought to determine whether a rift in the corneal epithelial surface would increase the risk of corneal adherence and infection by collagen-binding S. aureus.Previous animal models of staphylococcal keratitis used direct intrastromal injection to infect the cornea (1, 2, 5, 7, 9). However, direct inoculation into the corneal stroma does not allow the investigation of bacterial adherence to the corneal surface, a critical initial event in the pathogenesis of microbial keratitis. Because staphylococci attach to contact lenses (3), an animal model using soft contact lenses contaminated with S. aureus was developed to study the role of bacterial adherence in the initiation of keratitis. To enhance the risk of infection, we applied a high-inoculum challenge to surface-injured corneas. This model was then used to study the biological role of the collagen-binding adhesin in S. aureus keratitis by comparing the levels of virulence of a parental strain (Cna ϩ ), its isogenic mutant (Cna Ϫ ), and the isogenic mutant complemented with an intact version of the gene (cna) encoding the collagen-binding adhesin. We also studied the protective effect of applying adhesin analogs before bacterial challenge.Rabbit model of S. aureus keratitis. The animals used in this study were treated according to the criteria of the Association for Research in Vision and Ophthalmology Resolution on the U...

Pathogenesis of microbial keratitis

“…aureus surface adhesins, collectively known as MSCRAMMS (microbial surface components recognizing adhesive matrix molecules), have also been recognized to mediate bacterial adherence to host extracellular matrix components, collagen, fibronectin, fibrinogen, laminin and elastin [80]. [161]; studied the role of MSCRAMM Cna (collagen-binding adhesin) in S. aureus keratitis and concluded that collagen-binding adhesin is a virulence factor for S. aureus keratitis and is involved in the early events of pathogenesis of S. aureus infection of the cornea. Similarly, [80] Likewise, Streptococci colonize different sites on human body by expressing multiple adhesins and hence their attachment to human tissues is mediated by a diverse group of bacterial surface proteins, MSCRAMMS [60].…”

Streptococcus pyogenes Collagen Type I-binding Cpa Surface Protein

“…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).…”

Tenacibaculum sp. associated with winter ulcers in sea-reared Atlantic salmon Salmo salar

“…Like most bacteria in the Cytophaga-Flavobacterium-Bacteroides complex, they have proteolytic properties, and identification of large numbers of cells in collagenous tissue also indicates collagenophilia. A collagenbinding adhesin was shown to be a virulence factor for some strains of Staphylococcus aureus causing keratitis in de-epithelialized corneas in a rabbit model (Rhem et al 2000). Whether a similar mechanism is important for the virulence of our bacterium is not known.…”