Geographic diversity of the Streptococcus equi subsp. equi accessory genome: implications for vaccines and global surveillance.
Abstract: Strangles, caused by the host-adapted subsp. (. ), imposes significant welfare and economic losses on the equine industry worldwide. Understanding its genomic features, virulence-associated genes (VAGs), antimicrobial resistance (AMR) and mobile genetic elements (MGEs) is essential for disease control and vaccine development. This study aimed to characterize the accessory genome composition, geographic distribution of VAGs and MGEs, and AMR profiles of . by a large-scale genomic analysis of global publicly available . sequences. All publicly available . sequences in the Sequence Read Archive (SRA) database were retrieved and assembled. A total of 552 high-quality assemblies were obtained for further analysis. The strains originated from five continents (North/South America, Europe, Asia and Oceania). The geographical distribution of VAGs (analyzed using an in-house virulence factor database), antibiotic resistance gene (ARG) profiles, and the contribution of MGEs to . VAGs were analyzed in this study. The results revealed that . exhibited a closed pangenome with 1,661 core and 982 accessory genes. Among 71 identified VAGs, 40 were core VAGs, while accessory VAGs showed significant geographic variations, especially in nutritional/metabolic factor genes and exotoxin genes. No acquired ARGs were detected except a single gene encoding resistance to quaternary ammonium compounds. This study revealed a functional specialization of MGEs, where prophages carry superantigen genes (, ) and the hyaluronidase gene ; genomic islands (GIs) harbor iron acquisition genes ( cluster) and the gene encoding the T4SS coupling protein; and integrative conjugative elements (ICEs) carry the heme metabolism cluster (, ) and streptolysin S-associated genes (, ). The geographic variation of VAGs suggests regional adaptive pressures and supports genome streamlining in . . In conclusion, . exhibits a closed and streamlined genome, characteristic of host-adapted bacteria. There is a minimal acquisition of ARGs while key VAGs are retained. Prophages, GIs, and ICEs play specialized roles in VAG distribution. These findings provide insights into prioritizing VAGs for strangles vaccine development and surveillance of antigenic variation to mitigate vaccine escape.
Copyright © 2025 He, Khine, Song, Loubière and Butaye.
Publication Date: 2025-11-28 PubMed ID: 41394906PubMed Central: PMC12698419DOI: 10.3389/fvets.2025.1721958Google Scholar: Lookup
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Summary
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Overview
- This study investigated the genetic diversity of Streptococcus equi subsp. equi, the bacterium that causes strangles in horses, by analyzing its accessory genome from a global collection of samples.
- The research focused on understanding virulence genes, antimicrobial resistance, and mobile genetic elements to inform vaccine development and global disease surveillance strategies.
Background and Significance
- Pathogen and Disease: Streptococcus equi subsp. equi is a host-adapted bacterial subspecies causing strangles, a contagious equine disease with significant welfare and economic impacts worldwide.
- Need for Genomic Study: Understanding the bacterium’s genomic architecture, especially its virulence-associated genes (VAGs), antimicrobial resistance (AMR), and mobile genetic elements (MGEs), helps in crafting effective disease control, vaccine development, and monitoring potential vaccine escape.
Methodology
- Data Collection: The study compiled all publicly available genome sequences of Streptococcus equi subsp. equi from the Sequence Read Archive (SRA) database.
- Sample Size and Distribution: 552 high-quality genome assemblies were analyzed, representing strains from five continents: North America, South America, Europe, Asia, and Oceania.
- Analytical Focus:
- Characterization of the accessory genome and core genes.
- Geographic distribution analysis of virulence-associated genes (using a custom virulence factor database).
- Assessment of antibiotic resistance gene (ARG) profiles.
- Examination of the role of mobile genetic elements (prophages, genomic islands, integrative conjugative elements) in virulence gene distribution.
Key Findings
- Pangenome Structure:
- The bacterium has a closed pangenome consisting of 1,661 core genes present in all strains and 982 accessory genes variably present across strains.
- Virulence-Associated Genes (VAGs):
- Out of 71 identified VAGs, 40 were core (found in all strains).
- Accessory VAGs showed significant geographic variation, particularly in genes related to nutrition/metabolism and exotoxins.
- This variation suggests region-specific adaptation and possibly distinct ecological pressures shaping virulence profiles.
- Antimicrobial Resistance Genes (ARGs):
- No acquired antibiotic resistance genes were found except for a single gene conferring resistance to quaternary ammonium compounds (disinfectants).
- This minimal presence suggests limited antibiotic resistance acquisition in this host-adapted pathogen.
- Mobile Genetic Elements and Functional Specialization:
- Prophages: Carried superantigen genes (such as those termed seeH and seeI) and the hyaluronidase gene (hylP).
- Genomic Islands (GIs): Harbored iron acquisition genes (the equibactin cluster) and the gene encoding the type IV secretion system (T4SS) coupling protein.
- Integrative Conjugative Elements (ICEs): Carried genes involved in heme metabolism (e.g., the hemoglobin receptor and heme ABC transporter) and streptolysin S-associated genes (sag genes).
- This repartition indicates specialized roles of MGEs in mobilizing different virulence factors.
Interpretations and Implications
- Host Adaptation and Genome Streamlining: The closed and streamlined genome architecture aligns with adaptation to the equine host, balancing retention of key virulence traits with limited gene acquisition.
- Geographic Variation: Regional differences in accessory virulence genes imply evolutionary adaptation to local environments or host populations, which could influence disease severity and transmission.
- Vaccine Development: Identification of highly conserved core VAGs provides targets for broad-based vaccine development against strangles.
- Surveillance: Monitoring geographic variation in VAGs and MGEs can help detect antigenic changes that may lead to vaccine escape, guiding future vaccine design and deployment.
Conclusion
- Streptococcus equi subsp. equi maintains a largely conserved genome with key virulence factors held across global populations despite some regional variation in accessory genes.
- Minimal antibiotic resistance gene acquisition suggests current therapies remain effective, but ongoing surveillance is essential.
- The specialized roles of MGEs in distributing virulence traits enhance understanding of bacterial pathogenicity mechanisms.
- This comprehensive genomic insight supports informed strategies for developing effective vaccines and worldwide surveillance programs to control strangles in horses.
Cite This Article
APA
He L, Khine NO, Song J, Loubière C, Butaye P.
(2025).
Geographic diversity of the Streptococcus equi subsp. equi accessory genome: implications for vaccines and global surveillance.
Front Vet Sci, 12, 1721958.
https://doi.org/10.3389/fvets.2025.1721958 Publication
Researcher Affiliations
- Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
- Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
- Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
- Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
- Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
- Faculty of Veterinary Medicine, Department of Pathobiology, Pharmacology and Zoological Medicine, Ghent University, Merelbeke, Belgium.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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