Phage Endolysins as Promising and Effective Candidates for Use Against Uropathogenic Escherichia coli

The presented in silico and phylogenetic analysis of putative endolysins potentially produced by phages infecting uropathogenic Escherichia coli (UPEC) demonstrates their remarkable diversity. These proteins exhibit significant variations in sequence length, molecular weight, isoelectric point, and stability, as well as diverse functional domains determining their enzymatic activity, including lysin, lysozyme, hydrolase, amidase, and peptidase functions. Due to their predicted lytic properties, endolysins hold great promise in combating UPEC bacteria, including those within biofilms, which are often highly resistant to conventional treatments. Despite their potential, several challenges hinder the full utilization of endolysins. These include the relatively small number of identified proteins, challenges in the annotation process, and the scarcity of studies evaluating their efficacy in vitro and in vivo against Gram-negative bacteria. In this work, we emphasize these challenges while also underlining the potential of endolysins as an effective tool against UPEC infections. Their effectiveness could be significantly enhanced when combined with agents that disrupt the outer membrane of these bacteria, making them a promising alternative or complement to existing antimicrobial strategies. Further research is necessary to fully explore their therapeutic potential.