Novel Lytic Phages Protect Cells and Mice against Pseudomonas aeruginosa Infection
- 25 March 2021
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 95 (8)
- https://doi.org/10.1128/jvi.01832-20
Abstract
With the fast emergence of serious antibiotic resistance and the lagged discovery of novel antibacterial drugs, phage therapy for pathogenic bacterial infections has acquired great attention in the clinics. However, development of therapeutic phages also faces tough challenges, such as laborious screening and time to generate effective phage drugs since each phage may only lyse 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, PPY9, and TH15) with broad host ranges to lyse laboratory strains and clinical isolates of P. aeruginosa with multi-drug resistance (MDR) both in vitro and in mouse models. In addition, we analyzed critical genetic traits related to the high-level broad host 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 multi-drug resistant (MDR) Pseudomonas aeruginosa, and antibacterial capacity both in vitro and in mouse models. First, we characterized the genetic traits and compared with other existing phages. Furthermore, we utilized acute pneumonia induced by laboratorial strain PAO1, and W19, an MDR clinical isolate and chronic pneumonia by agar beads laden with FDR1, 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 the infection symptom 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.Keywords
This publication has 58 references indexed in Scilit:
- Phage Therapy as a Novel Strategy in the Treatment of Urinary Tract Infections Caused by E. ColiAntibiotics, 2020
- Current challenges and future opportunities of phage therapyFEMS Microbiology Reviews, 2020
- A megaplasmid family driving dissemination of multidrug resistance in PseudomonasNature Communications, 2020
- Loci Encoding Compounds Potentially Active against Drug-Resistant Pathogens amidst a Decreasing Pool of Novel AntibioticsApplied and Environmental Microbiology, 2019
- Risk Factors for Carbapenem-ResistantPseudomonas aeruginosa, Zhejiang Province, ChinaEmerging Infectious Diseases, 2019
- Carbapenem-Resistant Pseudomonas aeruginosa at US Emerging Infections Program Sites, 2015Emerging Infectious Diseases, 2019
- The complete genome sequence of Escherichia phage SRT7, a novel T7-like phageArchiv für die gesamte Virusforschung, 2019
- Predictive factors for multidrug-resistant gram-negative bacteria among hospitalised patients with complicated urinary tract infectionsAntimicrobial Resistance & Infection Control, 2018
- Bacteriophages ϕMR299-2 and ϕNH-4 Can Eliminate Pseudomonas aeruginosa in the Murine Lung and on Cystic Fibrosis Lung Airway CellsmBio, 2012
- Antibacterial Efficacy of Phages against Pseudomonas aeruginosa Infections in Mice and Drosophila melanogasterAntimicrobial Agents and Chemotherapy, 2009