Novel Lytic Phages Protect Cells and Mice against Pseudomonas aeruginosa Infection

With the fast emergence of serious antibiotic resistance and the lagging discovery of novel antibacterial drugs, phage therapy for pathogenic bacterial infections has acquired great attention in clinics. However, the development of therapeutic phages also faces tough challenges such as the laborious screening and time to generate effective phage drugs since each phage may lyse only a narrow scope of bacterial strains. Identifying highly effective phages with broad host ranges is crucial for improving phage therapy. Here, we isolated and characterized several lytic phages from various environments specific for Pseudomonas aeruginosa by testing their growth, invasion, host ranges, and potential for killing targeted bacteria. Importantly, we identified several therapeutic phages (HX1, MYY9, and TH15) with broad host ranges to lyse laboratory strains and clinical isolates of P. aeruginosa with multidrug resistance (MDR) both in vitro and in mouse models. In addition, we analyzed critical genetic traits related to high-level broad-host-range coverages by genome sequencing and subsequent computational analysis against known phages. Collectively, our findings establish that these novel phages may have potential for further development as therapeutic options for patients who fail to respond to conventional treatments. IMPORTANCE Novel lytic phages isolated from various environmental settings were systematically characterized for their critical genetic traits, morphology structures, host ranges against laboratory strains and clinical multidrug-resistant (MDR) Pseudomonas aeruginosa isolates, and antibacterial capacity both in vitro and in mouse models. First, we characterized the genetic traits and compared them with those of other existing phages. Furthermore, we utilized acute pneumonia induced by laboratory strain PAO1 and strain W-19, an MDR clinical isolate, and chronic pneumonia by agar beads laden with FRD1, a mucoid-phenotype strain isolated from the sputum of a cystic fibrosis (CF) patient. Consequently, we found that these phages not only suppress bacteria in vitro but also significantly reduce infection symptoms and disease progression in vivo, including lowered bug burdens, inflammatory responses, and lung injury in mice, suggesting that they may be further developed as therapeutic agents against MDR P. aeruginosa.