Search

Antimicrobial resistance is an escalating threat with few new therapeutic options in the pipeline. Urinary tract infections (UTIs) are one of the most prevalent bacterial infections globally and are prone to becoming recurrent and antibiotic resistant. We discovered and characterized six novel Autographiviridae and Guernseyvirinae bacterial viruses (phage) against uropathogenic Escherichia coli (UPEC), a leading cause of UTIs. The phage genomes were between 39,471 bp - 45,233 bp, with 45.0%–51.0% GC%, and 57–84 predicted coding sequences per genome. We show that tail fiber domain structure, predicted host capsule type, and host antiphage repertoire correlate with phage host range. In vitro characterisation of phage cocktails showed synergistic improvement against a mixed UPEC strain population and when sequentially dosed. Together, these phage are a new set extending available treatments for UTI from UPEC, and phage vM_EcoM_SHAK9454 represents a promising candidate for further improvement through engineering. • UTIs from antibiotic resistant uropathogenic E. coli (UPEC) are recurrent and difficult to eliminate. • Six novel Autographiviridae and Guernseyvirinae phages were isolated from UPEC hosts. • Phage cocktails showed synergistic improvement against a mixed UPEC strain population. • Sequential phage treatment was improvement over single phage treatment. • Host range differences were explained by predicted tail fiber/spike structure, LPS/capsules, and host antiphage repertoire. [ABSTRACT FROM AUTHOR]

Abstract: Lytic coliphage vB_EcoP_G7C and several other highly related isolates were obtained repeatedly from the samples of horse feces held in the same stable thus representing a component of the normal indigenous intestinal communities in this population of animals. The genome of G7C consists of 71,759bp with terminal repeats of about 1160bp, yielding approximately 73 kbp packed DNA size. Seventy-eight potential open reading frames, most of them unique to N4-like viruses, were identified and annotated. The overall layout of functional gene groups was close to that of the original N4 phage, with some important changes in late gene area including new tail fiber proteins containing hydrolytic domains. Structural proteome analysis confirmed all the predicted subunits of the viral particle. Unlike N4 itself, phage G7C did not exhibit a lysis-inhibited phenotype. [Copyright &y& Elsevier]

Abstract: Our analysis of the plague diagnostic phage L-413C genome sequence and structure reveals that L-413C is highly similar and collinear with enterobacteriophage P2, though important differences were found. Of special interest was the mosaic nature of the tail fiber protein H in L-413C, given the differentiating specificity of this phage for Yersinia pestis vs. Yersinia pseudotuberculosis. While the N-terminal 207 and C-terminal 137 amino acids of L-413C display significant homology with the P2 H protein, a large (465 amino acid) middle section appears to be derived from a T4-related H protein, with highest similarity to the T6 and RB32 distal tail fibers. This finding along with appropriate preadsorption experiments suggest that the unique H protein of L-413C may be responsible for the specificity of this phage for Y. pestis, and that the Y. pestis receptors that are recognized and bound by L-413C either do not exist in Y. pseudotuberculosis or have a different structure. [Copyright &y& Elsevier]