A Lytic Providencia rettgeri Virus of Potential Therapeutic Value Is a Deep-Branching Member of the <i>T5virus</i> Genus

Abstract

<i>Providencia rettgeri</i> is emerging as a new opportunistic pathogen with high antibiotic resistance. The need to find alternative methods to control antibiotic-resistant bacteria and the recent advances in phage therapy motivate the search for new phages able to infect <i>Providencia</i> spp. This study describes the isolation and characterization of an obligatory lytic phage, vB_PreS_PR1 (PR1), with therapeutic potential against drug-resistant <i>P. rettgeri</i> PR1 is a siphovirus. Its virion DNA size (118,537 bp), transcriptional organization, terminal repeats (10,461 bp), and nicks in the 3'-to-5' strand are similar to those of phage T5. However, sequence similarities of PR1 to phages of the <i>T5virus</i> genus at the DNA and protein levels are limited, suggesting that it belongs to a new species within the <i>Siphoviridae</i> family. PR1 exhibits the ability to kill <i>P. rettgeri</i> antibiotic-resistant strains, is highly specific to the species, and did not present known genomic markers indicating a temperate lifestyle. The lack of homologies between its proteins and proteins of the only other sequenced <i>Providencia</i> prophage, Redjac, suggests that these two phages evolved separately and may target different host proteins.<b>IMPORTANCE</b> The alarming increase in the number of bacteria resistant to antibiotics has been observed worldwide. This is particularly true for Gram-negative bacteria. For certain of their strains, no effective antibiotics are available. <i>Providencia</i> sp. has been a neglected pathogen but is emerging as a multidrug-resistant bacterium. This has revived interest in bacteriophages as alternative therapeutic agents against this bacterium. We describe the morphological, physiological, and genomic characterization of a novel lytic virus, PR1, which is able to kill drug-resistant <i>P. rettgeri</i> clinical isolates. Genomic and phylogenetic analyses indicate that PR1 is a distant relative of <i>T5virus</i> genus representatives. The lack of known virulence- or temperate lifestyle-associated genes in the genome of PR1 makes this phage a potential candidate for therapeutic use. Analysis of its genome also improves our knowledge of the ecology and diversity of T5-like siphoviruses, providing a new link for evolutionary studies of this phage group.