New Bacteriophages with Podoviridal Morphotypes Active against Yersinia pestis: Characterization and Application Potential

Abstract

Phages of highly pathogenic bacteria represent an area of growing interest for bacterial detection and identification and subspecies typing, as well as for phage therapy and environmental decontamination. Eight new phages—YpEc56, YpEc56D, YpEc57, YpEe58, YpEc1, YpEc2, YpEc11, and YpYeO9—expressing lytic activity towards Yersinia pestis revealed a virion morphology consistent with the Podoviridae morphotype. These phages lyse all 68 strains from 2 different sets of Y. pestis isolates, thus limiting their potential application for subtyping of Y. pestis strains but making them rather promising in terms of infection control. Two phages—YpYeO9 and YpEc11—were selected for detailed studies based on their source of isolation and lytic cross activity towards other Enterobacteriaceae. The full genome sequencing demonstrated the virulent nature of new phages. Phage YpYeO9 was identified as a member of the Teseptimavirus genus and YpEc11 was identified as a member of the Helsettvirus genus, thereby representing new species. A bacterial challenge assay in liquid microcosm with a YpYeO9/YpEc11 phage mixture showed elimination of Y. pestis EV76 during 4 h at a P/B ratio of 1000:1. These results, in combination with high lysis stability results of phages in liquid culture, the low frequency of formation of phage resistant mutants, and their viability under different physical–chemical factors indicate their potential for their practical use as an antibacterial mean.

Phylogenetic Relationships and Evolution of the Genus Eganvirus (186-Type) Yersinia pestis Bacteriophages

“…Many phages can lyse Y. pestis, including lytic phages previously called Podoviridae phages (such as Pokrovskaya [40], A1122 [41], and Yep-phi [42]), as well as eight recently reported new phages with Podoviridae characteristics (YpEc56, YpEc56D, YpEc57, YpEe58, YpEc1, YpEc2, YpEc11, and YpYeO9) [43]. Because several such phages have specific lytic effects on Y. pestis, some are routinely used for the diagnosis of this disease.…”

“…This consistency was not only observed in terms of genomic arrangement (99-100%), but also in high homology to conserved structural genes. One interesting phenomenon is that when the apl and cI genes were compared, the phage GCS667 clustered apart from other Eganvirus phages, and instead GCS667 clustered with the phages Many phages can lyse Y. pestis, including lytic phages previously called Podoviridae phages (such as Pokrovskaya [40], A1122 [41], and Yep-phi [42]), as well as eight recently reported new phages with Podoviridae characteristics (YpEc56, YpEc56D, YpEc57, YpEe58, YpEc1, YpEc2, YpEc11, and YpYeO9) [43]. Because several such phages have specific lytic effects on Y. pestis, some are routinely used for the diagnosis of this disease.…”

A Bacteriophage Cocktail TargetingYersinia pestisProvides Strong Post-Exposure Protection in a Rat Pneumonic Plague Model

“…Several previous studies have shown in vitro phage efficacy against Y. pestis (22–24); however, a few studies have demonstrated in vivo efficacy (25, 26). In one study, phage treatment was shown to delay progression of pneumonic plague; however, all mice still succumbed unless antibiotic therapy was co-administered (26).…”