T-even-related bacteriophages as candidates for treatment of Escherichia coli urinary tract infections

Abstract

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 degrees 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.

Phage therapy of Cronobacter-induced urinary tract infection in mice

“…The observed 70% reduction of Cronobacter colonies in the kidneys 24 hours after a single phage dose is consistent with other similar results observing phage efficacy in the treatment of wound infections [32]. The ability of phages to survive in the urinary tract 24 hours after administration has already been shown [33]. There was no difference in Cronobacter colonization of the bladder between treated and infected groups.…”

Efficacy of Bacteriophage Therapy in Experimental Sepsis and Meningitis Caused by a Clone O25b:H4-ST131 Escherichia coli Strain Producing CTX-M-15

“…Whether different phages have various abilities to resist human serum inactivation remains to be evaluated; we suggest that future assessments of experimental phage therapy should include this evaluation. Pharmacokinetic properties of phage in experimental models using adult mice have been described previously (19,31,36,40,44) but, to our knowledge, they have never been studied in a neonatal murine model. Our data indicated that EC200 PP was partially retained by spleen and kidney, where phage concentrations were at any time as high or higher than in blood, especially after intraperitoneal injection, as in mouse models (19,31,36).…”

“…Though used for decades in Eastern Europe, successful phage therapy has been demonstrated only recently in experimental models (8,11,15,27,36,40,43,44). Because bacteriophage replicate at infection sites, efficacy may require just a single dose (23,40).…”

Bacteriophages and Their Derivatives as Biotherapeutic Agents in Disease Prevention and Treatment

“…After seven days, 100 and 90% of mice treated with T4 and KEP10, respectively, had survived. In the control group, where no phages were administered, all the mice died within three days [78]. In addition, lower multiplicities of infection (0.03 and 0.003) resulted in a reduced rescue of animals (60 and 40%) [79].…”