Design of a Bacteriophage Cocktail Active against <i>Shigella</i> Species and Testing of Its Therapeutic Potential in <i>Galleria mellonella</i>
Andrey A. Filippov,
Wanwen Su,
Kirill V. Sergueev,
Richard T. Kevorkian,
Erik C. Snesrud,
Apichai Srijan,
Yunxiu He,
Derrick E. Fouts,
Woradee Lurchachaiwong,
Patrick T. McGann,
Damon W. Ellison,
Brett E. Swierczewski,
Mikeljon P. Nikolich
Affiliations
Andrey A. Filippov
Wound Infections Department, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Wanwen Su
Wound Infections Department, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Kirill V. Sergueev
Wound Infections Department, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Richard T. Kevorkian
Wound Infections Department, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Erik C. Snesrud
Multidrug-Resistant Organism Repository and Surveillance Network, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Apichai Srijan
Department of Enteric Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand
Yunxiu He
Wound Infections Department, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Derrick E. Fouts
J. Craig Venter Institute, Rockville, MD 20850, USA
Woradee Lurchachaiwong
Department of Enteric Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand
Patrick T. McGann
Multidrug-Resistant Organism Repository and Surveillance Network, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Damon W. Ellison
Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Brett E. Swierczewski
Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Mikeljon P. Nikolich
Wound Infections Department, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Shigellosis is a leading global cause of diarrheal disease and travelers’ diarrhea now being complicated by the dissemination of antibiotic resistance, necessitating the development of alternative antibacterials such as therapeutic bacteriophages (phages). Phages with lytic activity against Shigella strains were isolated from sewage. The genomes of 32 phages were sequenced, and based on genomic comparisons belong to seven taxonomic genera: Teetrevirus, Teseptimavirus, Kayfunavirus, Tequatrovirus, Mooglevirus, Mosigvirus and Hanrivervirus. Phage host ranges were determined with a diverse panel of 95 clinical isolates of Shigella from Southeast Asia and other geographic regions, representing different species and serotypes. Three-phage mixtures were designed, with one possessing lytic activity against 89% of the strain panel. This cocktail exhibited lytic activity against 100% of S. sonnei isolates, 97.2% of S. flexneri (multiple serotypes) and 100% of S. dysenteriae serotypes 1 and 2. Another 3-phage cocktail composed of two myophages and one podophage showed both a broad host range and the ability to completely sterilize liquid culture of a model virulent strain S. flexneri 2457T. In a Galleria mellonella model of lethal infection with S. flexneri 2457T, this 3-phage cocktail provided a significant increase in survival.
