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Applied and Environmental Microbiology, July 2008, p. 4149-4163, Vol. 74, No. 13
0099-2240/08/$08.00+0     doi:10.1128/AEM.02371-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

In Silico and In Vivo Evaluation of Bacteriophage EF24C, a Candidate for Treatment of Enterococcus faecalis Infections ^,

Departments of Pediatrics,¹ Microbiology and Infection, Kochi Medical School, Oko-cho, Nankoku City, Kochi 783-8505, Japan²

Received 22 October 2007/ Accepted 1 April 2008

Along with the increasing threat of nosocomial infections by vancomycin-resistant Enterococcus faecalis, bacteriophage (phage) therapy has been expected as an alternative therapy against infectious disease. Although genome information and proof of applicability are prerequisites for a modern therapeutic phage, E. faecalis phage has not been analyzed in terms of these aspects. Previously, we reported a novel virulent phage, EF24C, and its biology indicated its therapeutic potential against E. faecalis infection. In this study, the EF24C genome was analyzed and the in vivo therapeutic applicability of EF24C was also briefly assessed. Its complete genome (142,072 bp) was predicted to have 221 open reading frames (ORFs) and five tRNA genes. In our functional analysis of the ORFs by use of a public database, no proteins undesirable in phage therapy, such as pathogenic and integration-related proteins, were predicted. The noncompetitive directions of replication and transcription and the host-adapted translation of the phage were deduced bioinformatically. Its genomic features indicated that EF24C is a member of the SPO1-like phage genus and especially that it has a close relationship to the Listeria phage P100, which is authorized for prophylactic use. Thus, these bioinformatics analyses rationalized the therapeutic eligibility of EF24C. Moreover, the in vivo therapeutic potential of EF24C, which was effective at a low concentration and was not affected by host sensitivity to the phage, was proven by use of sepsis BALB/c mouse models. Furthermore, no change in mouse lethality was observed under either single or repeated phage exposures. Although further study is required, EF24C can be a promising therapeutic phage against E. faecalis infections.

Published ahead of print on 2 May 2008.

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