Design of a Bacteriophage Cocktail Active against Shigella Species and Testing of Its Therapeutic Potential in Galleria mellonella

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

doi:10.3390/antibiotics11111659

Antibiotics (Nov 2022)

Design of a Bacteriophage Cocktail Active against Shigella Species and Testing of Its Therapeutic Potential in Galleria mellonella

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

DOI: https://doi.org/10.3390/antibiotics11111659
Journal volume & issue: Vol. 11, no. 11
p. 1659

Abstract

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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.

Published in Antibiotics

ISSN: 2079-6382 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.mdpi.com/journal/antibiotics

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