Therapeutic potential of bacteriophage in treating Klebsiella pneumoniae B5055-mediated lobar pneumonia in mice

Abstract

Klebsiella pneumoniae causes infections in humans especially in immunocompromised patients. About 80 % of nosocomial infections caused by K. pneumoniae are due to multidrug-resistant strains. The emergence of antibiotic-resistant bacterial strains necessitates the exploration of alternative antibacterial therapies, which led our group to study the ability of bacterial viruses (known as bacteriophages or simply phages) to treat mice challenged with K. pneumoniae. Phage SS specific for K. pneumoniae B5055 was isolated and characterized, and its potential as a therapeutic agent was evaluated in an experimental model of K. pneumoniae-mediated lobar pneumonia in mice. Mice were challenged by intranasal (i.n.) inoculation with bacteria (108 c.f.u. ml−1). A single intraperitoneal injection of 1010 p.f.u. ml−1 phage administered immediately after i.n. challenge was sufficient to rescue 100 % of animals from K. pneumoniae-mediated respiratory infections. Administration of the phage preparation 3 h prior to i.n. bacterial challenge provided significant protection in infected mice, while even 6 h delay of phage administration after the induction of infection rendered the phage treatment ineffective. The results of this study therefore suggest that the timing of starting the phage therapy after initiation of infection significantly contributes towards the success of the treatment.

Bacteriophages and Their Derivatives as Biotherapeutic Agents in Disease Prevention and Treatment

“…A single intraperitoneal injection of 10 10 CFU/mL phage SS administered immediately after intranasal inoculation challenge was sufficient to rescue 100% of animals from the K. pneumoniae-mediated respiratory infections [80]. In addition, in a rabbit model of wound infection, abscess formation in rabbits was prevented when 2 × 10 9 PFU of phage LS2a was injected simultaneously with 8 × 10…”

wksl3, a New Biocontrol Agent for Salmonella enterica Serovars Enteritidis and Typhimurium in Foods: Characterization, Application, Sequence Analysis, and Oral Acute Toxicity Study

“…Generally, phages are found near the host bacteria (53) and recognize specific bacterial hosts (54). While the emergence of pathogenic bacteria with increasing resistance to currently used antimicrobial agents is growing, phages have now resurfaced as potential biocontrol and therapeutic agents (55)(56)(57)(58)(59)(60). The majority of human-infecting Salmonella strains originate from poultry and poultry-derived food products (61).…”

Bacteriophage PPST1 Isolated from Hospital Wastewater, A Potential Therapeutic Agent Against Drug Resistant Salmonella enterica subsp. enterica serovar Typhi

“…They have been used for therapeutic purposes since the 1920s. Several studies have shown that bacteriophages could be used successfully for therapeutic purposes both in humans and animals (Bruttin & Brussow, 2005;Chhibber et al, 2008;Deresinski, 2009;Nakai & Park, 2002). In addition, there have been several reports showing the ability of lytic bacteriophages to kill drug resistant bacteria (Capparelli et al, 2007;Thamniamton et al, 2010;Vinodkumar et al, 2005).…”