In Vitro and In Vivo Evaluation of Three Newly Isolated Bacteriophage Candidates, phiEF7H, phiEF14H1, phiEF19G, for Treatment of Enterococcus faecalis Endophthalmitis

Abstract

Post-operative endophthalmitis caused by Enterococcus spp. progresses rapidly and often results in substantial and irreversible vision loss. Therefore, novel alternative treatments that are effective against enterococcal endophthalmitis are required. Bacteriophage therapy has the potential to be an optional therapy for infectious diseases. Therefore, we investigated the therapeutic potential of three newly isolated enterococcal phages, phiEF7H, phiEF14H1, and phiEF19G, in E. faecalis-induced endophthalmitis. These phages could lyse the broad-range E. faecalis, including strains derived from endophthalmitis and vancomycin-resistant E. faecalis in vitro, as determined by the streak test. Morphological and genomic analyses revealed that these phages were classified into the Herelleviridae genus Kochikohdavirus. The whole genomes of these phages contained 143,399, 143,280, and 143,400 bp, respectively. Endophthalmitis was induced in mice by injection of three strains of E. faecalis derived from post-operative endophthalmitis or vancomycin-resistant strains into the vitreous body. The number of viable bacteria and infiltration of neutrophils in the eye were both decreased by intravitreous injection of phiEF7H, phiEF14H1, and phiEF19G 6 h after injection of all E. faecalis strains. Thus, these results suggest that these newly isolated phages may serve as promising candidates for phage therapy against endophthalmitis.

Bacteriolytic Potential of Enterococcus Phage iF6 Isolated from “Sextaphag®” Therapeutic Phage Cocktail and Properties of Its Endolysins, Gp82 and Gp84

“…The chromosome of iF6 is a dsDNA molecule with a length of 156,592 bp and two direct terminal repeats of 2108 bp each ( Figure 5 and Figure 8 c). Similar organization of both virions and genomes has been described in phages infecting enterococci [ 38 , 39 , 40 , 41 , 42 , 43 ].…”

“…A mixture of EFKL1 and EFDG1 killed E. faecalis in an in vivo model of rat root canal infection [ 50 ]. A cocktail of three phages, phiEF7H, phiEF14H1 and phiEF19G, closely related members of the genus Kochikohdavirus , was highly effective against endophthalmitis caused by vancomycin-resistant E. faecalis in both in vivo and in vitro models [ 40 ]. The EF1TV phage was able to eradicate biofilms formed by clinical isolates of E. faecalis [ 47 ].…”

Enterococcal Phages: Food and Health Applications

“…Several studies have evaluated the efficacy of phage therapy in an E. faecalis sepsis mice model using intraperitoneal injections. The intraperitoneal administration of phage IME-EF1 or its endolysin, at a 10 MOI, 30 min after E. faecalis 002 inoculation resulted in survival rates of 60% and 80%, respectively [143]. A single injection of 3 × 10 8 PFU of the phage ENB6, administered 45 min after a vancomycin-resistant E. faecium (CRMEN 44) challenge, was able to rescue 100% of the mice [144].…”

Intracameral Bacteriophage Injection as Postoperative Prophylaxis for Enterococcus faecalis–Induced Endophthalmitis After Cataract Surgery in Rabbits

“…We have previously reported the therapeutic effects of phage therapy in a mouse model of ocular bacterial infections, including phage eye drops for Pseudomonas aeruginosa keratitis and phage vitreous injection for enterococcal endophthalmitis. 13 – 15 However, there have been no reports investigating phage therapy as a prophylactic to prevent endophthalmitis.…”