PMID:18456848

Citation	Uchiyama, J, Rashel, M, Takemura, I, Wakiguchi, H and Matsuzaki, S (2008) In silico and in vivo evaluation of bacteriophage phiEF24C, a candidate for treatment of Enterococcus faecalis infections. Appl. Environ. Microbiol. 74:4149-63
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, phiEF24C, and its biology indicated its therapeutic potential against E. faecalis infection. In this study, the phiEF24C genome was analyzed and the in vivo therapeutic applicability of phiEF24C 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 phiEF24C 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 phiEF24C. Moreover, the in vivo therapeutic potential of phiEF24C, 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, phiEF24C can be a promising therapeutic phage against E. faecalis infections.
Links	PubMed PMC2446516 Online version:10.1128/AEM.02371-07
Keywords	Animals; Bacteriophages/genetics; Bacteriophages/physiology; Disease Models, Animal; Enterococcus faecalis/pathogenicity; Enterococcus faecalis/virology; Female; Genome, Viral; Gram-Positive Bacterial Infections/microbiology; Gram-Positive Bacterial Infections/mortality; Gram-Positive Bacterial Infections/therapy; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Sepsis/microbiology; Sepsis/mortality; Sepsis/therapy; Sequence Analysis, DNA; Treatment Outcome
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
BPPHE:VPN2		GO:0019012: virion	ECO:0000247:	PMID:18456848	C		Matched 99.3% with BBP17, major capsid protein (A new topology of the HK97-like fold revealed in Bordetella bacteriophage: non-covalent chainmail secured by jellyrolls) with an E-value of 7.5E-13. Figure 2 of the PubMed article shows the phylogenetic analyses of bacteriophage φEF24C. It shows a phylogenetic tree accompanied by comparisons of the genes between φEF24C and Listeria phage P100. In the figure the two bacteriophages are connected by a black line with a blast E-value that is less than 0.1.	complete CACAO 11881

References

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