The Generation of an ocular anti-inflammatory biotherapeutic to enhance wound healing

Abstract

Microbes exist at and colonize mucosal surfaces striking a balance with the host immune system, so that these microbes can thrive on host tissues without causing pathology. Because of this, mucosal barrier-colonizing bacteria can be leveraged to act as long-term delivery vehicles for naturally derived therapeutics. Here, we use a mouse model of corneal wound healing to show that the eye-colonizing bacterium, Corynebacterium mastitidis (C. mast) can be engineered to produce and secrete bioactive murine anti-inflammatory interleukin (mIL)-10. Specifically, we used transposon mutagenesis to identify a native C. mast-specific secretion signal that was used to direct C. mast to secrete mIL-10. Mini-transposons were generated to deliver secretion capable mIL-10 to the bacterial genome. After screening, two isolates were identified that can: 1) colonize the eye, 2) produce and secrete mIL-10, and 3) enhance wound healing in an IL-10-dependent manner. This proof of concept illustrates that eye-colonizing bacteria can be engineered to deliver therapeutics to the ocular surface for the alleviation of ocular surface disease(s).