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In Silico and In Vivo Evaluation of Bacteriophage φEF24C, a Candidate for Treatment of Enterococcus faecalis Infections

Author:
Uchiyama, Jumpei, Rashel, Mohammad, Takemura, Iyo, Wakiguchi, Hiroshi, Matsuzaki, Shigenobu
Source:
Applied and environmental microbiology 2008 v.74 no.13 pp. 4149-4163
ISSN:
0099-2240
Subject:
Enterococcus faecalis, Listeria, alternative medicine, bacteriophages, bioinformatics, cross infection, databases, genes, hosts, infectious diseases, mice, models, open reading frames, prediction, proteins, transfer RNA
Abstract:
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, φEF24C, and its biology indicated its therapeutic potential against E. faecalis infection. In this study, the φEF24C genome was analyzed and the in vivo therapeutic applicability of φEF24C 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 φEF24C 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 φEF24C. Moreover, the in vivo therapeutic potential of φEF24C, 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, φEF24C can be a promising therapeutic phage against E. faecalis infections.
Agid:
551803