A Novel Phage Cocktail Therapy of the Urinary Tract Infection in a Mouse Model

Abstract

Escherichia coli (E. coli) is a major bacterial pathogen associated with many cases of serious infections, such as urinary tract infections (UTI) and meningitis intestinal. The rapid emergence of antimicrobial multidrug-resistant bacteria occurring worldwide has been attributed to the overuse of antibiotics. Alternative strategies must be developed to overcome antibiotic resistance. A promising alternative for the treatment of infections is the use of phages as antibacterial agents. A total of 90 female albino mice were randomly divided into three groups (n=30) and used for the induction of UTI. The animals were acclimatized in their cages for 24 h before inoculation and allowed to access chow and water freely. For UTI induction, the peri-urethral area was sterilized with 70% ethanol, and bacterial inoculation was then injected into the bladder through the urethra using a 24-gauge sterile Teflon catheter with an outer diameter of 0.7 mm and length of 19 mm. A single phage and a phage cocktail preparation have been evaluated for their therapeutic activity in the mouse model of chronic UTI induced by transurethral injection of two isolates of the uropathogenic E. coli 8 and E. coli 302. The results of the transurethral and intra-peritoneal injection of phage(s) that prepared on day 10 after the establishment of the mouse chronic model showed no effect of a single phage PEC80 in the treatment of UTI, whereas both administration routes of the phage cocktail preparation resulted in the clearance of bacteria from mice urine and homogenates of the urinary bladders and kidneys of the sacrificed mice after 24 h following the administration of phage cocktail dose. The high activity of the phage cocktail in the treatment of mouse chronic model of UTI is attributed to the broader host range of the phage cocktail, compared to the very narrow host range of the phage PEC80. It is concluded that the phage therapy by using phage preparations as the 25 phages cocktail evaluated in this study is a highly promising and potential alternative therapy for human UTIs.

Keywords: Alternative Therapy; Drug Resistance; Phage Cocktail; Phage Therapy; UTI.

Figure 1

Culture results of the bladder homogenates of mice sacrificed on days 1, 3, 5, 10, 15, 20, 25, and 30 of infection establishment for both mice with traumatized bladder mucosa (♦) and non-traumatized bladder mucosa (■)

Figure 2

Culture results of kidney homogenates of mice sacrificed on days 1, 3, 5, 10, 15, 20, 25, and 30 of infection establishment for both mice with traumatized bladder mucosa (♦) and non-traumatized bladder mucosa (■)

Figure 3

Culture results of bladder and kidney homogenates of mice sacrificed on days 10, 11, 12, 13, 14, and 15of the infection establishment after transurethral administration of single phage preparation of phage PEC80 on day 10

Figure 4

Culture results of bladder and kidney homogenates of mice sacrificed on days 10, 11, 12, 13, 14, and 15 of the infection establishment after intraperitoneal administration of phage cocktail preparation on day 10

Figure 5

Culture results of bladder homogenates of mice sacrificed on days10, 11, 12, 13, 14, and 15 of the infection establishment after transurethral administration of phage preparation on day 10. Mice injected with phage cocktail preparation (♦), and mice injected with single phage preparation (■)

Figure 6

Culture results of kidney homogenates of mice sacrificed on days 10, 11, 12, 13, 14, and 15 of the infection establishment after intraperitoneal administration of phage preparation on day 10. Mice injected with phage cocktail preparation (♦), and mice injected with single phage preparation (■)

Figure 7

Culture results of bladder homogenates of mice sacrificed on days 10, 11, 12, 13, 14, and 15 of the infection establishment after intraperitoneal administration of phage preparation on day 10. Mice injected with phage cocktail preparation (♦), and mice injected with single phage preparation (■)

Figure 8

Culture results of kidney homogenates of mice sacrificed on days 10, 11, 12, 13, 14, and 15 of the infection establishment after intraperitoneal administration of phage preparation on day 10. Mice injected with phage cocktail preparation (♦), and mice injected with single phage preparation (■)