Novel Anti-Microbial/Anti-Inflammatory Combination Improves Clinical Outcome of Bacillus cereus Endophthalmitis.

PURPOSE

The purpose of this study was to explore the therapeutic potential of the novel combination of Bacillus bacteriophage lysin (PlyB) and a synthetic TLR2/4 inhibitor (oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, OxPAPC) in the treatment of experimental Bacillus cereus endophthalmitis.

METHODS

C57BL/6J mice were injected with 100 colony forming units (CFUs) Bacillus cereus to induce endophthalmitis. Two hours postinfection, groups of mice were treated with either PlyB, PlyB with OxPAPC, or the groups were left untreated to serve as a control. A group of uninfected mice was injected with only PlyB to serve as a treatment control. Eight hours post-treatment, infected/treated mice were analyzed for bacterial counts, retinal function, histology, and inflammation.

RESULTS

Groups treated with PlyB alone or PlyB/OxPAPC showed significantly reduced bacterial loads compared with untreated eyes. Compared with untreated eyes, PlyB and PlyB/OxPAPC-treated eyes retained significant A-wave and B-wave function. PlyB/OxPAPC-treated eyes retained greater A- and B-wave function compared with eyes treated with PlyB alone. Histology showed that retinal structures were well preserved, and retinal layers were distinguishable in eyes treated with PlyB and PlyB/OxPAPC. Ninety-five percent of infiltrating CD45+ cells in infected untreated eyes were Ly6G+/Ly6C+ neutrophils. Infected eyes treated with PlyB and PlyB/OxPAPC had significantly reduced numbers of CD45+ immune cells compared with untreated eyes. Eyes treated with PlyB/OxPAPC had a significantly lower number of neutrophils than eyes treated with PlyB alone.

CONCLUSIONS

These results demonstrated that the novel combination of bacteriophage lysin and TLR2/4 inhibitor was a successful treatment option for treating experimental Bacillus cereus endophthalmitis.