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.

Comparative virulence and antimicrobial resistance distribution of Streptococcus suis isolates obtained from the United States

“…Some recent studies have undertaken whole-genome sequencing (WGS) in combination with comparative genomic approaches to evaluate the genomic diversity and AMR elements harbored by S. suis isolates ( Weinert et al, 2015 ; Wileman et al, 2019 ; Hadjirin et al, 2021 ; Estrada et al, 2022 ). The majority of these genomic sequences needed to evaluate potential risks attributed to the capacity of S. suis isolates to successfully function as zoonotic agents and/or reservoirs for AMR dissemination, is derived from isolates obtained outside the U.…”

“…The majority of these genomic sequences needed to evaluate potential risks attributed to the capacity of S. suis isolates to successfully function as zoonotic agents and/or reservoirs for AMR dissemination, is derived from isolates obtained outside the U. S ( Weinert et al, 2015 ; Wileman et al, 2019 ; Hadjirin et al, 2021 ; Estrada et al, 2022 ). The goals of the current study were to fill this gap by utilizing whole-genome sequencing (WGS) analysis to evaluate the sequence type (ST) and serotype distribution of S. suis isolates obtained within the U.S., screen genomes for genomic elements encoding AMR, determine whether or not identified AMR genes are located within MGEs, and screen for genomic elements encoding factors known to increase or contribute to the capacity of S. suis to transmit, colonize, and/or cause disease in humans.…”

Genomic differences between sequence types 1 and 104 of Streptococcus suis Serotype 2

“…In addition, analysis of the virulence-associated genes showed that many of them were present in the ST1 strain ID26154 ( Table 3 ). Three proposed novel marker genes ( SSU_RS03100 : hypothetical protein, SSU_RS09155 : hypothetical protein, and SSU-RS09525 : RNA-binding protein) for predicting the pathogenic pathotype of S. suis were also present in our ST1 strain (100% identity), suggesting these are also present in Asian or Eurasian strains ( Table 3 ; Estrada et al, 2022 ). However, further study needs to be evaluated for these marker genes with S. suis strains from different geographical origins.…”

“…Our ST104 strain contains genes that may be associated with virulence in the ST1 and ST7 strains, as shown in Table 3 ( Fittipaldi et al, 2012 ; Takamatsu et al, 2009 ; Zhang et al, 2009 ; Dumesnil et al, 2018 ). It carries three proposed novel marker genes ( SSU_RS03100 : hypothetical protein, SSU_RS09155 : hypothetical protein, and SSU-RS09525 : RNA-binding protein; Estrada et al, 2022 ) that predict pathogenicity of S. suis , suggesting that this ST104 strain presents a pathogenic pathotype ( Table 3 ; Estrada et al, 2022 ).…”

“…The virulence factor database (VFDB) was used to identify virulence genes in the ST1 and ST104 genomes ( Liu et al, 2019 ). Two marker genes (G15: sigma-70 and G20: relaxase mobilization nuclease domain protein) specific to human-associated clade (HAC; Dong et al, 2021 ) and novel-candidate virulence genes associated with the pathogenic pathotype of S. suis ( SSU_RS03100 : hypothetical protein, SSU_RS09155 : hypothetical protein, and SSU-RS09525 : RNA-binding protein; Estrada et al, 2022 ) were used to analyze their presence in the ST1 and ST104 genomes used in the current study based on MyDBFinder 2.0 ( ).…”