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Immunization with homologous Pseudomonas aeruginosa pili protects against ocular disease
X L Rudner1, R S Berk, L D Hazlett
1Department of Anatomy/Cell Biology, Wayne State University, Detroit, MI 48201.
Abstract:
The prophylactic effect of pili in prevention or amelioration of Pseudomonas aeruginosa ocular disease was examined in mice, using both systemic and topical protection approaches. At 30 days postinfection, a significant number of animals actively or passively immunized with pili homologous to pseudomonal strain American Type Culture Collection 19660 were protected from ocular disease when compared with similarly infected phosphate-buffered saline controls. Although exogenously mixing strain 19660 with either homologous or heterologous (PAK/PR1) pili before topical application of the inoculum significantly inhibited bacterial adhesion in vitro, in similarly designed in vivo studies, animals were not protected from corneal disease. Neither was significant ocular protection conferred using pili (PAK/PR1) heterologous to the infecting strain (19660) for active or passive immunization of mice, nor in studies involving exogenous mixing of PAK/PR1 pili or its pili-specific monoclonal antibody with strain 19660 prior to topical application of the latter. These results provide evidence that significant ocular protection is achieved by either active or passive, but not topical, immunization with pili homologous to the infecting bacterial strain and that immunization with pili heterologous to the infecting bacterial strain fails to provide protection against ocular disease, despite the fact that heterologous pili are highly effective at decreasing bacterial binding to cornea in vitro.
Insights
Active or passive immunization with homologous pili protected mice from Pseudomonas aeruginosa ocular disease. Heterologous pili failed to protect against ocular disease, despite reducing bacterial adhesion in vitro.
Area of Science:
- Ophthalmology
- Microbiology
- Immunology
Background:
- Pseudomonas aeruginosa is a common cause of bacterial keratitis.
- Pili are protein appendages on bacteria that mediate adhesion and infection.
- The role of pili in preventing P. aeruginosa ocular disease requires further investigation.
Purpose of the Study:
- To evaluate the prophylactic efficacy of pili against Pseudomonas aeruginosa ocular infections in a mouse model.
- To compare the effectiveness of systemic (active/passive immunization) versus topical pili application.
- To assess the impact of homologous versus heterologous pili on infection outcomes.
Main Methods:
- Mice were subjected to systemic or topical immunization with homologous or heterologous pili prior to P. aeruginosa infection.
- Bacterial adhesion was assessed in vitro by mixing bacteria with pili.
- Ocular disease severity and bacterial load were evaluated post-infection.
Main Results:
- Active or passive immunization with pili homologous to the infecting strain (ATCC 19660) significantly protected mice from ocular disease.
- Topical application of homologous or heterologous pili did not prevent corneal disease in vivo.
- Immunization or topical application with heterologous pili (PAK/PR1) did not confer ocular protection, despite in vitro inhibition of bacterial adhesion.
Conclusions:
- Homologous pili administered systemically (active/passive immunization) provide significant protection against P. aeruginosa ocular disease.
- Topical pili application is ineffective for preventing P. aeruginosa keratitis.
- Heterologous pili are ineffective for ocular disease prevention, even if they inhibit bacterial binding in vitro.