In situ forming hydrogel loaded with predatory bacteria treats drug-resistant corneal infection

Abstract

The development of potent bactericidal antibiotic alternatives is important to address the current antibiotic crisis. A representative example is the topical delivery of predatory Bdellovibrio bacteriovorus bacteria to treat ocular bacterial infection. However, the direct topical use of B. bacteriovorus suspensions has the problem of easy loss and inactivation. Here, a B. bacteriovorus in situ forming hydrogel (BIG) was constructed for the ocular delivery of B. bacteriovorus. BIGs, as a fluid in their primitive state, were temperature- and cation- dually sensitive, which was rapidly transformed into immobile gels in the ocular environment. BIGs not only kept the activity of B. bacteriovorus but also retained on the ocular surface for a long time. The biosafety of BIGs was good without HCEC cell toxicity and hemolysis. More importantly, BIGs highly inhibited the growth of drug-resistant Pseudomonas aeruginosa whether in vitro or in the infected rat eyes. The ocular infection was completely controlled by BIGs with no corneal ulcers and inflammations. This living bacteria gel is a promising medication for the local treatment of drug-resistant bacteria-induced ocular infection.