Phage Endolysins and Their Derived Antimicrobial Peptide: Alternative Antimicrobials to Combat Antibiotic Resistant Ocular Infections

Abstract

Purpose : Emerging antibiotic resistance among ocular pathogens jeopardizes the clinical management of eye infections. Thus, there is a need for new antimicrobials to combat drug resistant infections. Bacteriophage (phage) endolysins are peptidoglycan hydrolases that are released at the end of the phage lytic cycle to digest host bacterial cell wall and facilitate the release of mature phage progeny. The aim of this study is to determine the susceptibility of phage endolysins and their derived antimicrobial peptides towards ocular isolates of S. aureus and A. baumannii.

Methods : The antimicrobial activity of recombinant phage endolysins or their synthetic derived antimicrobial peptides was determined against human endophthalmitis isolates of S. aureus (n=20) and 12 ocular surface colonizing isolates of A. baumannii. Antimicrobial activity was assessed by MIC determination and turbidity reduction. Effect of phage endolysins on biofilm dispersal, was performed on bacterial biofilms made on glass coverslips by incubating with desired endolysin or peptide followed by staining with Live/Dead Baclight kit. Images of dead/live bacteria were captured by fluorescence microscopy. The bacterial killing in planktonic form was assessed by serial dilution and plate count following endolysin/peptide treatment.

Results : All S. aureus endophthalmitis isolates growing planktonically were significantly killed by recombinant endolysin Ply187. Moreover, the killing activity showed a time-dependent decrease in the turbidity. In the case of A. baumannii, derived antimicrobial peptide exerted strong anti-microbial activity against all 12 isolates whereas the lytic activity of phage endolysin varied among isolates. The bacterial biofilms formed by both S. aureus and A. baumannii were significantly dispersed by both phage endolysin and the derived antimicrobial peptide treatment compared to untreated controls.

Conclusions : Our data show that phage lysins or their synthetic derived antimicrobial peptides are quite effective against both Gram-positive and Gram-negative ocular pathogens, indicating that their antimicrobial properties can be harnessed to treat resistant eye infections.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.