Isolation of phages infecting the zoonotic pathogen Streptococcus suis reveals novel structural and genomic
Emmanuel Kuffour Osei1,2,3, Reuben O'Hea1, Christian Cambillau1,2,4
1School of Microbiology, University College Cork, Co. Cork, T12 K8AF, Ireland.
Abstract:
Bacteriophage research has experienced a renaissance in recent years, owing to their therapeutic potential and versatility in biotechnology, particularly in combating antibiotic resistant-bacteria along the farm-to-fork continuum. However, certain pathogens remain underexplored as targets for phage therapy, including the zoonotic pathogen Streptococcus suis which causes infections in pigs and humans. Despite global efforts, the genome of only one infective S. suis phage has been described. Here, we report the isolation of two phages that infect S. suis: Bonnie and Clyde. The phages infect 58% of 100 S. suis strains tested, including representatives of seven different serotypes and thirteen known sequence types from diverse geographical origins. Clyde suppressed bacterial growth in vitro within two multi-strain mixes designed to simulate a polyclonal S. suis infection. Both phages demonstrated stability across various temperatures and pH levels, highlighting their potential to withstand storage conditions and maintain viability in delivery formulations. Genome comparisons revealed that neither phage shares significant nucleotide identity with any cultivated phages in the NCBI database and thereby represent novel species belonging to two distinct novel genera. This study is the first to investigate the adhesion devices of S. suis infecting phages. Structure prediction and analysis of adhesion devices with AlphaFold2 revealed two distinct lineages of S. suis phages: Streptococcus thermophilus-like (Bonnie) and S. suis-like (Clyde). The structural similarities between the adhesion devices of Bonnie and S. thermophilus phages, despite the lack of nucleotide similarity and differing ecological niches, suggest a common ancestor or convergent evolution, highlighting evolutionary links between pathogenic and non-pathogenic streptococcal species. These findings provide valuable insights into the genetic and phenotypic characteristics of phages that can infect S. suis, providing new data for the therapeutic application of phages in a One Health context.
Insights
Two novel bacteriophages, Bonnie and Clyde, were isolated and characterized, effectively targeting the zoonotic pathogen Streptococcus suis. These phages show promise for phage therapy against antibiotic-resistant bacteria in a One Health approach.
Area of Science:
- Microbiology
- Virology
- Biotechnology
Background:
- Bacteriophage research is rapidly advancing, particularly for combating antibiotic-resistant bacteria.
- Streptococcus suis, a zoonotic pathogen, remains an underexplored target for phage therapy, with limited genomic data on infective phages.
Purpose of the Study:
- To isolate and characterize novel bacteriophages targeting Streptococcus suis.
- To evaluate the therapeutic potential and genetic novelty of these phages for combating S. suis infections.
Main Methods:
- Isolation and characterization of two S. suis-infecting phages (Bonnie and Clyde).
- In vitro efficacy testing against multiple S. suis strains and stability assessments (temperature, pH).
- Whole-genome sequencing and comparative analysis, including adhesion device structure prediction using AlphaFold2.
Main Results:
- Bonnie and Clyde infect 58% of tested S. suis strains across diverse serotypes and sequence types.
- Clyde demonstrated in vitro suppression of bacterial growth in simulated polyclonal infections.
- Phages represent novel species in distinct genera, with unique adhesion devices suggesting evolutionary links to other streptococcal phages.
Conclusions:
- The isolated phages are novel and possess broad infectivity against S. suis.
- Their stability and efficacy suggest significant potential for phage therapy applications.
- This study provides crucial genetic and phenotypic data for S. suis phage therapy within a One Health framework.
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