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Comparative analysis of Streptococcus suis genomes identifies novel candidate virulence-associated genes in North American isolates.

ABSTRACT: Streptococcus suis is a significant economic and welfare concern in the swine industry. Pan-genome analysis provides an in-silico approach for the discovery of genes involved in pathogenesis in bacterial pathogens. In this study, we performed pan-genome analysis of 208 S. suis isolates classified into the pathogenic, possibly opportunistic, and commensal pathotypes to identify novel candidate virulence-associated genes (VAGs) of S. suis. Using chi-square tests and LASSO regression models, three accessory pan-genes corresponding to S. suis strain P1/7 markers SSU_RS09525, SSU_RS09155, and SSU_RS03100 (>95% identity) were identified as having a significant association with the pathogenic pathotype. The proposed novel SSU_RS09525 + /SSU_RS09155 + /SSU_RS03100 + genotype identified 96% of the pathogenic pathotype strains, suggesting a novel genotyping scheme for predicting the pathogenicity of S. suis isolates in North America. In addition, mobile genetic elements carrying antimicrobial resistance genes (ARGs) and VAGs were identified but did not appear to play a major role in the spread of ARGs and VAGs.

SUBMITTER: Estrada AA

PROVIDER: S-EPMC8932342 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Comparative analysis of Streptococcus suis genomes identifies novel candidate virulence-associated genes in North American isolates.

Estrada April A AA Gottschalk Marcelo M Gebhart Connie J CJ Marthaler Douglas G DG

Veterinary research 20220318 1

Streptococcus suis is a significant economic and welfare concern in the swine industry. Pan-genome analysis provides an in-silico approach for the discovery of genes involved in pathogenesis in bacterial pathogens. In this study, we performed pan-genome analysis of 208 S. suis isolates classified into the pathogenic, possibly opportunistic, and commensal pathotypes to identify novel candidate virulence-associated genes (VAGs) of S. suis. Using chi-square tests and LASSO regression models, three ...[more]

PMID: 35303917

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Project description:Streptococcus suis is a zoonotic bacterial swine pathogen causing substantial economic and health burdens to the pork industry worldwide. Most S. suis genome sequences available in public databases are from isolates obtained outside the United States. We sequenced the genomes of 106 S. suis isolates from the U.S. and analyzed them to identify their potential to function as zoonotic agents and/or reservoirs for antimicrobial resistance (AMR) dissemination. The objective of this study was to evaluate the genetic diversity of S. suis isolates obtained within the U.S., for the purpose of screening for genomic elements encoding AMR and any factors that could increase or contribute to the capacity of S. suis to transmit, colonize, and/or cause disease in humans. Forty-six sequence types (STs) were identified with ST28 observed as the most prevalent, followed by ST87. Of the 23 different serotypes identified, serotype 2 was the most prevalent, followed by serotype 8 and 3. Of the virulence genes analyzed, the highest nucleotide diversity was observed in sadP, mrp, and ofs. Tetracycline resistance was the most prevalent phenotypic antimicrobial resistance observed followed by macrolide-lincosamide-streptogramin B (MLSB) resistance. Numerous AMR elements were identified, many located within MGE sequences, with the highest frequency observed for ble, tetO and ermB. No genes encoding factors known to contribute to the transmission, colonization, and/or causation of disease in humans were identified in any of the S. suis genomes in this study. This includes the 89 K pathogenicity island carried by the virulent S. suis isolates responsible for human infections. Collectively, the data reported here provide a comprehensive evaluation of the genetic diversity among U.S. S. suis isolates. This study also serves as a baseline for determining any potential risks associated with occupational exposure to these bacteria, while also providing data needed to address public health concerns.

Project description: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.

Dataset Information

Comparative analysis of Streptococcus suis genomes identifies novel candidate virulence-associated genes in North American isolates.

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Comparative analysis of Streptococcus suis genomes identifies novel candidate virulence-associated genes in North American isolates.

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