Phage Therapy of Pseudomonas aeruginosa Infection in a Mouse Burn Wound Model

Abstract

Mice compromised by a burn wound injury and subjected to a fatal infection with Pseudomonas aeruginosa were administered a single dose of a Pseudomonas aeruginosa phage cocktail consisting of three different P. aeruginosa phages by three different routes: the intramuscular (i.m.), subcutaneous (s.c.), or intraperitoneal (i.p.) route. The results of these studies indicated that a single dose of the P. aeruginosa phage cocktail could significantly decrease the mortality of thermally injured, P. aeruginosa-infected mice (from 6% survival without treatment to 22 to 87% survival with treatment) and that the route of administration was particularly important to the efficacy of the treatment, with the i.p. route providing the most significant (87%) protection. The pharmacokinetics of phage delivery to the blood, spleen, and liver suggested that the phages administered by the i.p. route were delivered at a higher dose, were delivered earlier, and were delivered for a more sustained period of time than the phages administered by the i.m. or s.c. route, which may explain the differences in the efficacies of these three different routes of administration.Pseudomonas aeruginosa plays a prominent role as an etiological agent of serious infections in patients with burn wounds. Acute burn wounds cause a breach in the protective skin barrier and suppress the immune system, rendering the patients highly susceptible to bacterial infection. P. aeruginosa colonization of severe burn wounds and its rapid proliferation within the damaged tissues often lead to disseminated infections, resulting in bacteremia and septic shock (8,20) and high rates of mortality and morbidity. Treatment of such infections is confounded by the innate and acquired resistance of P. aeruginosa to many antimicrobials (8,15). It has been estimated that at least 50% of all deaths caused by burns are the result of infection (8), and untreatable infections have become a tragically frequent occurrence in patients infected with P. aeruginosa (9). Hence, the development of new therapeutic and prophylactic strategies for the control of bacterial infection in patients with burn wounds is needed.An alternative or supplement to antibiotic therapy, which is currently being reexamined, is the use of bacterial viruses (phage/bacteriophage) to target bacterial infections, i.e., phage therapy (13, 16-18, 22, 29, 30-32). Soothill examined the ability of bacteriophage to prevent the rejection of skin grafts of experimentally infected guinea pigs (27). His findings demonstrated that the phage-treated grafts were protected in six of seven cases, while untreated grafts failed uniformly, suggesting that phage might be useful for the prevention of P. aeruginosa infections in patients with burn wounds. However, while multiple studies have demonstrated the benefits of phage therapy for a variety of bacterial infections in animal model systems (3-7, 10, 14, 19, 23-26, 33-35), little documentation exists with regard to the treatment of burn wound infections (2). In the study described ...

CpG Motif in Phage Genome DNA Enhanced the Efficacy of Phage Therapy by Immunostimulation

“…This means the protection level and also adaptive immunity might be enhanced by CpG contained Ф DNA administration. Our findings are consistent with similar studies [17] has proved activation of innate immunity by exposing mice to the single dose of CpG DNA provide long-term protection (for two weeks) against multiple pathogens, including Listeria monocytogenes, Francisells tubarsis, Anthrax, ebola, malaria, Leshmania, and Schisoma [18,[22][23]. In the current study, we were unable to determine the prolonged (more than six weeks) protective effect of immunized animals due to scarification of them for antisera.…”

Characterization and Detection of Endolysin Gene from Three Acinetobacter baumannii Bacteriophages Isolated from Sewage Water

“…Phage therapy is one potential candidate for the treatment of multidrug resistant bacteria [5]. Clinical trials of bacteriophages and their derivatives as potential alternative agents for controlling multi drug resistance infection have been described in various bacterial pathogens [6][7][8][9]. Bacteriophages are able to replicate in the host cell and produce endolysin to lyse the host cell.…”

Innovative methods of biofilm treatment in chronic wounds

“…oraz Krylov i wsp. wykazały skuteczność bakteriofagów w leczeniu ran zakażonych przez P. aeruginosa [50][51][52].…”