Identification of a broad-spectrum lytic Bordetella phage and assessments of its potential for combating Bordetella infections

Abstract

Bordetella bronchiseptica (Bb) is a zoonotic respiratory pathogen that frequently causes infections in farming and companion animals, posing threats to agricultural economics and public health. However, Bb strains are intrinsically resistant to several antibiotics commonly used to treat respiratory infections. Phage therapy has been recognized as a promising strategy to combat bacterial infections. In this study, a novel Bordetella phage, designated PY223, was isolated using Bb strains as indicators. Genome network analysis with different phages showed PY223 was related to 15 viral clusters but was not included in any of these clusters. PY223 did not carry any known genes involved in lysogeny and/or horizontal gene transfer. Host range analysis showed that PY223 exhibited the capacity to lyse 70 Bb strains isolated from pigs and/or cats. Measurement of the one-step growth curve showed that PY223 had an incubation period of 10 min and a rapid growth period of 80 min. The burst size was estimated to be approximately 10⁹ PFU/cell. In addition, PY223 displayed the capacity to inhibit the growth of Bb for up to 17 h. PY223 was stable under environmental temperatures ranging from 4 °C to 60 °C and/or pH values between 5.0 and 9.0. It remained stable even when exposed to UV light for 30 min. Notably, PY223 effectively eliminated Bb biofilms, inhibited the growth of prophage-harboring Bb strains, and cleared Bb from the environment. In vivo testing in mouse models highlighted its excellent potential for treating respiratory Bordetella infections.