Bacteriophages as potential antibacterial agents in the treatment of the Burkholderia cepacia complex.

摘要

Bacteriophage therapy has received renewed attention due to the emergence of highly antibiotic resistant bacterial pathogens. The members of the Burkholderia cepacia complex (BCC) constitute one such group of bacterial pathogens that are particularly associated with debilitating respiratory infections in patients with cystic fibrosis and chronic granulomatous disease. The development of a phage therapy strategy for BCC infections was initiated by isolating and characterizing phages with activity against BCC bacteria and determining the efficacy of these phages as antibacterial agents in experimental infection models. Over ten phages were isolated and characterized by host range analysis, electron microscopy, genome restriction analysis, and partial DNA sequencing. In order to demonstrate that phages can be used effectively to kill BCC bacteria in experimental models, we first developed the Galleria mellonella infection model for the BCC. The G. mellonella model overcomes many of the detriments of pre-existing BCC alternative infection models, and provides a cost-effective, user-friendly, practical alternative for studying BCC bacteria. We observed differences in pathogenicity between both species and strains of the BCC, and these results compared favorably with results acquired using other published alternative infection models, as well as mammalian infection models. The potential of phage therapy for experimental BCC infections was evaluated using the G. mellonella model. We observed that several phages were quite effective in vivo for example a single injection of phage KS12 to larvae infected with a lethal dose of a clinically isolated BCC strain resulted in over 90% larval survival. In order to corroborate the results obtained using the G. mellonella infection model, the applicability of phage therapy for experimental pulmonary infections in mice was assessed. Our findings indicate that phage therapy has the potential to be effective against the BCC in vivo, and therefore, at least for highly antibiotic resistant bacterial pathogens, strengthens the argument for the development and use of phage therapy as an alternative clinical treatment.