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Mihaela G Gadjeva; Targeting ocular P. aeruginosa biofilms. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1547.
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P. aeruginosa is a among the most frequent pathogens associated with bacterial keratitis. It induces disease that progresses quickly and in majority of cases causes loss of visual acuity. With the rise of antibiotic resistance, the need for novel treatments is quickly recognized.
To suggest novel therapeutic approaches, we utilized in vivo confocal imaging of the ocular infection in real time and compared host responses to infection in mice resistant to keratitis with the responses in mice that were susceptible to keratitis. Neutrophil proteomic signatures were characterized by quantitative protoemics.
We observed that during infection P. aeruginosa forms focal clusters in the cornea, which progressed to develop into biofilms. The ocular biofilms had a specific structure with bacteria moving within tracks that clustered together as sheets. Externally, biofilm edges were covered with psl, a P. aeruginosa secreted polysaccharide. PMNs surrounded the biofilms, but were not efficient at phagocytosing or destroying the bacterial clusters. Cumulatively, these data suggest that modalities that dissolve biofilms will facilitate neutrophil functionality. To this end, we propose that targeting psl will facilitate bacterial phagocytosis. We also suggest that utilizing enzymes in conjunction with MoAb therapy has therapeutic potential.
We think that these results will provide the ophthalmic community with a novel therapeutics to strengthen the host response to P. aeruginosa which can be used either independently or as an adjunctive modality along with antibiotics.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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