T-even-related bacteriophages as candidates for treatment of Escherichia coli urinary tract infections
- 278 Downloads
Multidrug-resistant uropathogenic Escherichia coli (UPEC) is increasing gradually on a worldwide scale. We therefore examined the possibility of bacteriophage (phage) therapy for urinary tract infections (UTIs) caused by the UPEC strains as an alternative to chemotherapy. In addition to the well-known T4 phage, KEP10, which was newly isolated, was used as a therapeutic phage candidate. KEP10 showed a broader bacteriolytic spectrum (67%) for UPEC strains than T4 (14%). Morphological and genetic analyses showed that KEP10 resembles phage T4. Phages T4 and KEP10 injected into the peritoneal cavity of mice were distributed immediately to all organs examined and maintained a high titer for at least 24 h. They were stable in the urine of both mice and humans for 24 h at 37°C. Administration of these phages into the peritoneal cavity caused a marked decrease in the mortality of mice inoculated transurethrally with a UPEC strain, whereas most of the control mice died within a few days of bacterial infection. Inoculation with phage alone produced no adverse effects attributable to the phage per se. The present study experimentally demonstrated the therapeutic potential of phage for E. coli-induced UTIs, and T-even-related phages may be suitable candidates with which to treat them.
KeywordsMajor Capsid Protein Phage Therapy Mouse Urine UPEC Strain Bacterial Infectious Disease
This work was partly supported by grants from the Ministry of Education, Science, Sports, and Culture, Japan .
- 4.Carlton RM (1999) Phage therapy: past history and future prospects. Arch Immunol Ther Exp 47:267–274Google Scholar
- 8.Glantz SA (2002) Primer of biostatistics, 5th edn. McGrau Hill Medical Publishing Division. New YorkGoogle Scholar
- 14.Matsuzaki S, Yasuda M, Nishikawa H, Kuroda M, Ujihara T, Shuin T, Shen Y, Jin Z, Fujimoto S, Nasimuzzaman MD, Wakiguchi H, Sugihara S, Sugiura T, Koda S, Muraoka A, Imai S (2003) Experimental protection of mice against lethal Staphylococcus aureus infection by novel bacteriophage ϕMR11. J Infect Dis 187:613–624PubMedCrossRefGoogle Scholar
- 20.Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring HarborGoogle Scholar
- 26.Summers WC (1999) Félix d’Herelle and the origins of molecular biology. Yale University Press, New HavenGoogle Scholar
- 31.Weber-Dabrowska B, Mulczyk M, Górski A (2000) Bacteriophage therapy of bacterial infections: an update of our institute’s experience. Arch Immunol Ther Exp 48:547–551Google Scholar