A single dose of a virulent bacteriophage vB PaeP-SaPL, rescues bacteremic mice infected with multi drug resistant Pseudomonas aeruginosa

Abstract

Multidrug resistant bacterial infections are difficult to treat and contribute to high morbidity and mortality. The phage vB PaeP-SaPL was isolated from a sewage drain (Lahore, Pakistan) against Pseudomonas aeruginosa PA-1 (NCBI Accession number MG763232). SaPL produced circular, transparent plaques, 4-5 mm in diameter and showed broad host range infecting 57 % of tested MDR P. aeruginosa clinical isolates (N = 38), while no infectivity was observed against any tested strains of other genera. SaPL inhibited PA-1 growth until 24 h post infection at MOI of 1. The SaPL showed stability at varying temperature and pH, with optimum stability at pH 7 and 45 °C. The latent period of SaPL was 20 min with burst size of 155 virions. The genome of SaPL was double stranded DNA of 45,796 bps having 63 CDS (13 for known proteins and 50 for hypothetical proteins) with a GC content of 52 %. The termini analysis revealed that SaPL genome ends are redundant and permuted. The packaging strategy used by SaPL was a headful (pac) strategy like P1 phage. Survivability of PA-1 challenged mice, treated with SaPL (100 %) was statistically significant (P < 0.05) than in untreated challenged mice (0%). Based on its efficacy in reducing bacterial growth, selective infectivity against majority of P. aeruginosa strains and its ability to increase survivability in PA-1 challenged mice, SaPL is proposed to be a potential candidate for bacteriophage therapy against difficult to treat MDR P. aeruginosa infections.

Keywords: Multi drug resistance; Phage therapy; Plaque forming unit (pfu); Sewage.