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Michelle Callegan, Phillip S Coburn, Hang Zhao, Valentin V Rybenkov; Role of Pseudomonas aeruginosa Condensins in Corneal Infection. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2347.
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Bacterial infections of the cornea can cause significant vision loss. The spread of multidrug-resistant bacteria necessitates the development of new antibiotics. Bacterial condensins govern chromosomal organization and thereby influence growth and virulence. In this study, we examined the P. aeruginosa condensins MksB and SMC as plausible therapeutic targets in corneal infections.
Corneas of C57BL/6J mice were scarified and infected with approximately 106 CFU of P. aeruginosa PAO1, an MksB-deficient mutant (Δmks), an SMC-deficient mutant (Δsmc), or a double mutant deficient in both condensins (Δmks/Δsmc). Infections were analyzed by bacterial quantitation, biomicroscopy, and histology on days 1, 2, and 3 post-infection to assess bacterial growth and inflammation. Values represent N ≥ 5 eyes/group.
PAO1 grew in C57BL/6J corneas to approximately 107 CFU/eye by day 3 post-infection and caused significant corneal inflammation over 3 days. Δsmc grew to approximately 107 CFU/eye by day 1 post-infection, but the corneal burden significantly declined on days 2 and 3, and no Δsmc were recovered from 3/5 eyes on day 3 post-infection. The Δmks corneal burden declined over 3 days, and no Δmks were recovered from 3/9 eyes on day 2 post-infection or from 2/5 eyes on day 3 post-infection. The Δmks/Δsmc corneal burden also declined over 3 days, and no Δmks/Δsmc were recovered from 3/9 eyes on day 1 post-infection, from 6/9 eyes on day 2 post-infection, or from 5/5 eyes on day 3 post-infection. Infection with Δsmc caused somewhat reduced corneal inflammation compared to that caused by PAO1. Infection with Δmks and Δmks/Δsmc did not cause corneal inflammation.
The results indicate that a deficiency in P. aeruginosa condensins arrests corneal virulence. These findings suggest that condensins may be a plausible target for therapeutic intervention. The exploration of condensins as a novel drug target is innovative, as broad-spectrum condensin inhibition would target a chromosome organization pathway not yet examined as a drug target.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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