Aerosol Phage Therapy Efficacy in Burkholderia cepacia Complex Respiratory Infections

Abstract

Phage therapy has been suggested as a potential treatment for highly antibiotic-resistant bacteria, such as the species of the Burkholderia cepacia complex (BCC). To address this hypothesis, experimental B. cenocepacia respiratory infections were established in mice using a nebulizer and a nose-only inhalation device. Following infection, the mice were treated with one of five B. cenocepacia-specific phages delivered as either an aerosol or intraperitoneal injection. The bacterial and phage titers within the lungs were assayed 2 days after treatment, and mice that received the aerosolized phage therapy demonstrated significant decreases in bacterial loads. Differences in phage activity were observed in vivo. Mice that received phage treatment by intraperitoneal injection did not demonstrate significantly reduced bacterial loads, although phage particles were isolated from their lung tissue. Based on these data, aerosol phage therapy appears to be an effective method for treating highly antibiotic-resistant bacterial respiratory infections, including those caused by BCC bacteria.

Burkholderia cepacia Complex Phage-Antibiotic Synergy (PAS): Antibiotics Stimulate Lytic Phage Activity

“…Optical density values were measured by using a Victor X3 spectrophotometric plate reader (PerkinElmer, Woodbridge, ON, Canada). Phages KS12 and KS14 were previously isolated and characterized by members of the Dennis laboratory, and those results were previously reported (22,26,42). Both phages KS12 and KS14 contain double-stranded DNA nucleic acids and are of the phage family Myoviridae (A1 morphotype).…”

“…Subinhibitory concentrations of antibiotics have been shown to produce an increase in phage activity (26)(27)(28)(29)(30)(31)(32)(33)(34)(35), and recently, this was termed "phage-antibiotic synergy," or PAS (33). In this study, we have tested ciprofloxacin (a fluoroquinolone antibiotic), meropenem (a carbapenem, which is a modified ␤-lactam antibiotic), and tetracycline (a protein translation inhibitor).…”

“…Phage therapy against Bcc infections has produced promising results both in G. mellonella larvae (22) and when delivered by aerosol into lungs in a mouse infection model (26). In this study, we have combined phage therapy with doses of antibiotics to observe PAS in the treatment of a Bcc infection in G. mellonella.…”

“…In a type of coevolutionary arms race, phages can rapidly adapt to counter improvements in bacterial resistance, which is in direct contrast to the long development time required for new static chemical antibiotics (21). Recent studies exploring the treatment of Bcc infections via phage therapy have demonstrated promise (22)(23)(24)(25)(26), including our recent study showing Bcc phage efficacy in a mouse infection model (26).…”

Identification of Diverse Mycoviruses through Metatranscriptomics Characterization of the Viromes of Five Major Fungal Plant Pathogens

“…Mycoviruses also have potential application in human health for the control of fungicide-resistant human pathogens, which can produce mycoses in immunocompromised patients (29,30). Analogous strategies are being investigated to control bacterial infections in humans using bacteriophages (31,32). To overcome resistance to bacteriophage that frequently develops in bacteria, the use of antimicrobial proteins expressed by bacteriophages (e.g., endolysins) has been examined for control of human bacterial diseases (33)(34)(35).…”