This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Uchiyama, J. Articles by Matsuzaki, S. Search for Related Content PubMed PubMed Citation Articles by Uchiyama, J. Articles by Matsuzaki, S. Agricola Articles by Uchiyama, J. Articles by Matsuzaki, S.

 Previous Article  |  Next Article 

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 ^,

Jumpei Uchiyama,^1,2 Mohammad Rashel,² Iyo Takemura,² Hiroshi Wakiguchi,¹ and Shigenobu Matsuzaki^2*

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.

---

* Corresponding author. Mailing address: Department of Microbiology and Infection, Kochi Medical School, Kohasu Oko-cho, Nankoku City, Kochi 783-8505, Japan. Phone: 81-88-880-2323. Fax: 81-88-880-2324. E-mail: matuzaki{at}kochi-u.ac.jp

Published ahead of print on 2 May 2008.

Supplemental material for this article may be found at http://aem.asm.org/.

---

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.

This article has been cited by other articles:

• Seed, K. D., Dennis, J. J. (2009). Experimental Bacteriophage Therapy Increases Survival of Galleria mellonella Larvae Infected with Clinically Relevant Strains of the Burkholderia cepacia Complex. Antimicrob. Agents Chemother. 53: 2205-2208 [Abstract] [Full Text]  
• Klumpp, J., Dorscht, J., Lurz, R., Bielmann, R., Wieland, M., Zimmer, M., Calendar, R., Loessner, M. J. (2008). The Terminally Redundant, Nonpermuted Genome of Listeria Bacteriophage A511: a Model for the SPO1-Like Myoviruses of Gram-Positive Bacteria. J. Bacteriol. 190: 5753-5765 [Abstract] [Full Text]