**2.1 Phage cocktails against UPEC**

Monophage therapy or using a single phage has an important limitation, which is a narrow host range. Phage cocktails use two or more phages for therapy making the host range broad and overcoming host bacterial resistance to phages. The phage cocktail or combination of phages to UPEC can recognize more than one host receptor and hence infect many uropathogenic strains. A phage cocktail of T4 phage and KEP10 phage was introduced in the peritoneal cavity of the mouse as the first therapeutic candidate for the treatment of UTI caused by UPEC [14]. The efficacy of T1, T4, and phiX174-like phages was also evaluated against UPEC. T1 phage was found to be the most effective in killing UPEC as it had a broad lytic spectrum; however, a combination of T1, T4, and phiX174 was capable of infecting a variety of antibiotic-tolerant UPEC strains [15]. A cocktail of nine phages without horizontal gene transfer and undesired genes from 99 T4-like coliphages to UPEC was used to produce a cocktail and given to 15 healthy adults. No side effects were seen, indicating that phage therapy was safe to use in UTIs [16]. In a study, it was seen that phage SP21 uses OmpC of *E. coli* 0157:H7 as a receptor, when this receptor was deleted, the phage-resistant bacteria emerged after 8 hrs of incubation. On modifying the lipopolysaccharide of the bacteria, the resistant bacteria emerged after 6 hrs of incubation with phage SP22. When a combination of two phages SP21 and SP22 binding to different host receptors of EHEC (*E. coli* 0157:H7) was used, it resulted in significant delay at the time of emergence of phage-resistant *E. coli* (upto 30 hrs) as compared to phages used alone [29]. Dual receptor phages to UPEC, which identify more than one receptor, have also been identified. Dual receptor phages to UPEC reported are T4 phages, T2 phages, and phage K1-5 of the family Podaviridae that infects both K1 and K5 strains of *E. coli* [17, 30, 31]. UPEC causes UTI by adhering to the urothelium producing biofilms successfully evading them from the host immune system and antibiotics. Phage cocktails have been found to be suitable for killing bacteria in biofilms. Biofilms of *E. coli* on the surface of polyvinyl chloride were susceptible to phage T4D+ [32]. Phage cocktails can be used for treating UTIs caused by *E. coli* biofilms present on urinary catheters. However, any mutational or conformational change in the host bacterial receptors can make the phages resistant to the bacteria, which is a limitation of using this strategy.


**Table 2.**

*Types of phage therapy for UPEC.*
