Abstract

BackgroundThere is limited information on the distribution of virulence-associated genes (VAGs) in U.S. Streptococcus suis isolates, resulting in little understanding of the pathogenic potential of these isolates. This lack also reduces our understanding of the epidemiology associated with S. suis in the United States and thus affects the efficiency of control and prevention strategies. In this study we applied whole genome sequencing (WGS)-based approaches for the characterization of S. suis and identification of VAGs.ResultsOf 208 S. suis isolates classified as pathogenic, possibly opportunistic, and commensal pathotypes, the genotype based on the classical VAGs (epf, mrp, and sly encoding the extracellular protein factor, muramidase-release protein, and suilysin, respectively) was identified in 9% (epf+/mrp+/sly+) of the pathogenic pathotype. Using the chi-square test and LASSO regression model, the VAGs ofs (encoding the serum opacity factor) and srtF (encoding sortase F) were selected out of 71 published VAGs as having a significant association with pathotype, and both genes were found in 95% of the pathogenic pathotype. The ofs+/srtF+ genotype was also present in 74% of ‘pathogenic’ isolates from a separate validation set of isolates.Pan-genome clustering resulted in the differentiation of a group of isolates from five swine production companies into clusters corresponding to clonal complex (CC) and virulence-associated (VA) genotypes. The same CC-VA genotype patterns were identified in multiple production companies, suggesting a lack of association between production company, CC, or VA genotype.ConclusionsThe proposed ofs and srtF genes were stronger predictors for differentiating pathogenic and commensal S. suis isolates compared to the classical VAGs in two sets of U.S. isolates. Pan-genome analysis in combination with metadata (serotype, ST/CC, VA genotype) was illustrated to be a valuable subtyping tool to describe the genetic diversity of S. suis.

Highlights

  • There is limited information on the distribution of virulence-associated genes (VAGs) in U.S Streptococcus suis isolates, resulting in little understanding of the pathogenic potential of these isolates

  • The training set was characterized by determination of serotype, multi-locus sequence typing (MLST), and clonal complex (CC)

  • The genetic diversity of isolates within and between swine production companies was evaluated by pan-genome analysis, and important associations were observed among pan-genome clusters, CCs, and virulence-associated (VA) genotypes

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Summary

Introduction

There is limited information on the distribution of virulence-associated genes (VAGs) in U.S Streptococcus suis isolates, resulting in little understanding of the pathogenic potential of these isolates. This lack reduces our understanding of the epidemiology associated with S. suis in the United States and affects the efficiency of control and prevention strategies. The numerous S. suis serotypes and STs limit our attempts to understand the epidemiology of the disease in an effort to prevent and manage the various clinical manifestations. The development of effective universal vaccines is hindered by the number of different virulent serotypes and the lack of knowledge of serotype- or STspecific virulence markers and associated clinical disease

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