Pyocin efficacy in a murine model of Pseudomonas aeruginosa sepsis

SynopsisO_ST_ABSBackgroundC_ST_ABSBloodstream infections with antibiotic resistant Pseudomonas aeruginosa are common and increasingly difficult to treat. Pyocins are naturally occurring protein antibiotics produced by P. aeruginosa that have potential for human use. ObjectivesTo determine if pyocin treatment is effective in a murine model of sepsis with P. aeruginosa. MethodsRecombinant pyocins S5 and AP41 were purified tested for efficacy in a Galleria mellonella infection model and a murine model of P. aeruginosa sepsis. ResultsBoth pyocins produced no adverse effects when injected alone into mice and showed good in vitro antipseudomonal activity. In an invertebrate model of sepsis using Galleria mellonella, both pyocins significantly prolonged survival. Following injection into mice, both showed extensive distribution into different organs. When administered 5 hours after infection, both pyocins reduced mortality, with pyocin S5 being more effective than AP41. ConclusionsPyocins S5 and AP41 show in vivo biological activity and can improve survival in a murine model of P. aeruginosa infection. They hold promise as novel antimicrobial agents for treatment of multi-drug resistant infections with this microbe.