Abstract

Shigellosis, caused by Shigella, is a major global health concern, with nearly 164.7 million cases and over a million deaths occurring annually worldwide. Shigella flexneri is one of the most common subgroups of Shigella with a high incidence of multidrug-resistance. The phage therapy approach is an effective method for controlling multidrug-resistant bacteria. However, only a few Shigella phages have been described to date. In this study, a novel lytic bacteriophage SFPH2 was isolated from a sewage sample obtained from a hospital in Beijing, China, using a multidrug-resistant S. flexneri 2a strain (SF2) isolated from the fecal sample of a dysentery patient. SFPH2 is a member of the Podoviridae virus family with an icosahedral capsid and a short, non-contractile tail. It was found to be stable over a wide range of temperatures (4–50°C) and pH values (pH 3–11). Moreover, SFPH2 could infect two other S. flexneri serotypes (serotypes 2 variant and Y). High-throughput sequencing revealed that SFPH2 has a linear double-stranded DNA genome of 40,387 bp with 50 open reading frames. No tRNA genes were identified in the genome. Comparative analysis of the genome revealed that the SFPH2 belongs to the subfamily Autographivirinae and genus T7virus. The genome shows high similarity with other enterobacterial T7virus bacteriophages such as Citrobacter phage SH4 (95% identity and 89% coverage) and Cronobacter phage Dev2 (94% identity and 92% coverage). A comparison of the fiber proteins showed that minor differences in the amino acid residues might specify different protein binding regions and determine host species. In conclusion, this is the first report of a T7virus that can infect Shigella; SFPH2 has a functional stability under a wide range of temperatures and pH values, showing the potential to be widely applied to control Shigella–associated clinical infections and reduce the transmission rates of S. flexneri serotype 2a and its variants in the environment.

Highlights

  • Shigellosis, an infectious diarrheal disease, is caused by the enteric pathogen Shigella

  • We report a novel Shigella lytic bacteriophage, SFPH2, which was isolated from a sewage sample using a multidrug-resistant S. flexneri 2a strain

  • A host range test was performed with SFPH2 on 131 S. flexneri, 20 Escherichia coli, 12 Salmonella typhimurium, one Salmonella enteritidis, and three Citrobacter freundii strains isolated from the fecal samples of patients with diarrhea or dysentery

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Summary

Introduction

Shigellosis, an infectious diarrheal disease, is caused by the enteric pathogen Shigella. It is a major worldwide health burden and causes nearly 164.7 million cases and over a million deaths every year, most of them occurring in developing countries (Kotloff et al, 1999). Serotypes 2 variant, Xv, and Yv are newly reported serotypes and are associated with epidemic-level disease (Ye et al, 2010; Sun et al, 2013; Qiu et al, 2015). The development of novel treatments or strategies has become an absolute necessity to control Shigella infections

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