Characterization and Genomic Analysis of SFPH2, a Novel T7virus Infecting Shigella

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.

Physicochemical characterization of ten newly isolated phages against the foodborne pathogen Shigella flexneri

“…In the present work, no viable particles were found when phage viability was assayed at pH 2 and 12 (data not shown). Other authors found similar results with other Shigella flexneri phages (Yang et al, 2018), some of them showing a high stability in alkaline conditions (Ahamed et al, 2019).…”

Isolation, phenotypic characterization and comparative genomic analysis of 2019SD1, a polyvalent enterobacteria phage

“…Compared to these findings, previously reported phages of Shigella such as pSf-1 52 , SH6 55 and Sfin-1 29 were infective under pH values ranging from 5 to 9, 5 to 11 and 5 to 12 respectively, but were less stable than 2019SD1. Contrastingly, compared to SfMu 25 and SFPH2 59 , 2019SD1 was less stable.

Figure 3 Stability of Shigella virus 2019SD1 under ( A ) Varying acidity and alkalinity levels, ( B ) Varying salinity (NaCl) concentrations and ( C ) Varying temperature regimes.

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“…Apparently, the mechanisms of host species determination and phage-receptor binding are far too complex and will attract attention of researchers for some time to come. Further research on these points may be useful for the development of artificial broad host range phages against multiple bacteria 59 . In the present study, the predicted protein of ORF 20 was identified as the putative tail assembly protein owing to 99.49% identity with that of Escherichia phage egaa.…”

Genomic and Proteomic Characterizations of Sfin-1, a Novel Lytic Phage Infecting Multidrug-Resistant Shigella spp. and Escherichia coli C

“…Although genomes of phages Sfin-1 , Shfl1 and pSf-2 were found to be highly similar as discussed above, they infect different species (Supplementary Table S2). As tail fiber proteins are involved in host range determination (Yang et al, 2018), the sequence and predicted features of three phages’ tail fiber proteins were compared. Four tail fiber proteins of Sfin-1 are (A) CDS61, (B) CDS67, (C) CDS71, and (D) CDS76.…”