1887

Abstract

colonizes the upper respiratory tract of healthy pigs at high abundance but can also cause opportunistic respiratory and systemic disease. Disease-associated reference strains are well studied, but less is known about commensal lineages. It is not known what mechanisms enable some lineages to cause disease while others persist as commensal colonizers, or to what extent gene expression in disease-associated and commensal lineages diverge. In this study we compared the transcriptomes of 21 . strains grown in active porcine serum and Todd–Hewitt yeast broth. These strains included both commensal and pathogenic strains, including several strains of sequence type (ST) 1, which is responsible for most cases of human disease and is considered to be the most pathogenic lineage. We sampled the strains during their exponential growth phase and mapped RNA sequencing reads to the corresponding strain genomes. We found that the transcriptomes of pathogenic and commensal strains with large genomic divergence were unexpectedly conserved when grown in active porcine serum, but that regulation and expression of key pathways varied. Notably, we observed strong variation of expression across media of genes involved in capsule production in pathogens, and of the agmatine deiminase system in commensals. ST1 strains displayed large differences in gene expression between the two media compared to strains from other clades. Their capacity to regulate gene expression across different environmental conditions may be key to their success as zoonotic pathogens.

Funding
This study was supported by the:
  • Horizon 2020 (Award 727966)
    • Principle Award Recipient: JerryM. Wells
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000992
2023-04-27
2024-05-04
Loading full text...

Full text loading...

/deliver/fulltext/mgen/9/4/mgen000992.html?itemId=/content/journal/mgen/10.1099/mgen.0.000992&mimeType=html&fmt=ahah

References

  1. Segura M, Aragon V, Brockmeier S, Gebhart C, Greeff A et al. Update on Streptococcus suis research and prevention in the era of antimicrobial restriction: 4th international workshop on S. suis. Pathogens 2020; 9:374 [View Article]
    [Google Scholar]
  2. Weinert LA, Chaudhuri RR, Wang J, Peters SE, Corander J et al. Erratum: genomic signatures of human and animal disease in the zoonotic pathogen Streptococcus suis. Nat Commun 2015; 6:7272 [View Article] [PubMed]
    [Google Scholar]
  3. Fredriksen S, Neila-Ibáñez C, Hennig-Pauka I, Guan X, Dunkelberger J et al. Streptococcus suis infection on European farms is associated with an altered tonsil microbiome and resistome. bioRxiv [View Article]
    [Google Scholar]
  4. Murase K, Watanabe T, Arai S, Kim H, Tohya M et al. Characterization of pig saliva as the major natural habitat of Streptococcus suis by analyzing oral, fecal, vaginal, and environmental microbiota. PLoS One 2019; 14:e0215983 [View Article] [PubMed]
    [Google Scholar]
  5. Fredriksen S, Guan X, Boekhorst J, Molist F, van Baarlen P et al. Environmental and maternal factors shaping tonsillar microbiota development in piglets. BMC Microbiol 2022; 22:224 [View Article] [PubMed]
    [Google Scholar]
  6. Murray GGR, Charlesworth J, Miller EL, Casey MJ, Lloyd CT et al. Genome reduction is associated with bacterial pathogenicity across different scales of temporal and ecological divergence. Mol Biol Evol 2021; 38:1570–1579 [View Article] [PubMed]
    [Google Scholar]
  7. Liang Z, Wu H, Bian C, Chen H, Shen Y et al. The antimicrobial systems of Streptococcus suis promote niche competition in pig tonsils. Virulence 2022; 13:781–793 [View Article] [PubMed]
    [Google Scholar]
  8. Ferrando ML, van Baarlen P, Orrù G, Piga R, Bongers RS et al. Carbohydrate availability regulates virulence gene expression in Streptococcus suis. PLoS One 2014; 9:e89334 [View Article] [PubMed]
    [Google Scholar]
  9. Atack JM, Weinert LA, Tucker AW, Husna AU, Wileman TM et al. Streptococcus suis contains multiple phase-variable methyltransferases that show a discrete lineage distribution. Nucleic Acids Res 2018; 46:11466–11476 [View Article] [PubMed]
    [Google Scholar]
  10. Zhong X, Ma J, Bai Q, Zhu Y, Zhang Y et al. Identification of the RNA-binding domain-containing protein RbpA that acts as a global regulator of the pathogenicity of Streptococcus suis serotype 2. Virulence 2022; 13:1304–1314 [View Article] [PubMed]
    [Google Scholar]
  11. Arenas J, Bossers-de Vries R, Harders-Westerveen J, Buys H, Ruuls-van Stalle LMF et al. In vivo transcriptomes of Streptococcus suis reveal genes required for niche-specific adaptation and pathogenesis. Virulence 2019; 10:334–351 [View Article] [PubMed]
    [Google Scholar]
  12. Ferrando ML, Gussak A, Mentink S, Gutierrez MF, van Baarlen P et al. Active human and porcine serum induce competence for genetic transformation in the emerging zoonotic pathogen Streptococcus suis. Pathogens 2021; 10:156 [View Article] [PubMed]
    [Google Scholar]
  13. Koczula A, Jarek M, Visscher C, Valentin-Weigand P, Goethe R et al. Transcriptomic analysis reveals selective metabolic adaptation of Streptococcus suis to porcine blood and cerebrospinal fluid. Pathogens 2017; 6:7 [View Article] [PubMed]
    [Google Scholar]
  14. Ni H, Li M, Wang Q, Wang J, Liu X et al. Inactivation of the htpsa gene affects capsule development and pathogenicity of Streptococcus suis. Virulence 2020; 11:927–940
    [Google Scholar]
  15. Zheng C, Wei M, Qiu J, Jia M, Zhou X et al. TroR negatively regulates the TroABCD system and is required for resistance to metal toxicity and virulence in Streptococcus suis. Appl Environ Microbiol 2021; 87:e0137521 [View Article] [PubMed]
    [Google Scholar]
  16. Zhong X, Zhang Y, Zhu Y, Dong W, Ma J et al. Identification of an autorepressing two-component signaling system that modulates virulence in Streptococcus suis serotype 2. Infect Immun 2019; 87:e00377-19 [View Article] [PubMed]
    [Google Scholar]
  17. Segura M, Fittipaldi N, Calzas C, Gottschalk M. Critical Streptococcus suis virulence factors: are they all really critical?. Trends Microbiol 2017; 25:585–599 [View Article] [PubMed]
    [Google Scholar]
  18. Wang J, Liang P, Sun H, Wu Z, Gottschalk M et al. Comparative transcriptomic analysis reveal genes involved in the pathogenicity increase of Streptococcus suis epidemic strains. Virulence 2022; 13:1455–1470 [View Article] [PubMed]
    [Google Scholar]
  19. Vecht U, Arends JP, van der Molen EJ, van Leengoed LA. Differences in virulence between two strains of Streptococcus suis type II after experimentally induced infection of newborn germ-free pigs. Am J Vet Res 1989; 50:1037–1043 [PubMed]
    [Google Scholar]
  20. Hadjirin NF, Miller EL, Murray GGR, Yen PLK, Phuc HD et al. Large-scale genomic analysis of antimicrobial resistance in the zoonotic pathogen Streptococcus suis. BMC Biol 2021; 19:191 [View Article] [PubMed]
    [Google Scholar]
  21. Wick RR, Judd LM, Gorrie CL, Holt KE. Unicycler: resolving bacterial genome assemblies from short and long sequencing reads. PLOS Comput Biol 2017; 13:e1005595 [View Article] [PubMed]
    [Google Scholar]
  22. Deng S, Xu T, Fang Q, Yu L, Zhu J et al. The surface-exposed protein SntA contributes to complement evasion in zoonotic Streptococcus suis. Front Immunol 2018; 9:1063 [View Article] [PubMed]
    [Google Scholar]
  23. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article] [PubMed]
    [Google Scholar]
  24. Bortolaia V, Kaas RS, Ruppe E, Roberts MC, Schwarz S et al. ResFinder 4.0 for predictions of phenotypes from genotypes. J Antimicrob Chemother 2020; 75:3491–3500 [View Article] [PubMed]
    [Google Scholar]
  25. Blin K, Shaw S, Steinke K, Villebro R, Ziemert N et al. antiSMASH 5.0: updates to the secondary metabolite genome mining pipeline. Nucleic Acids Res 2019; 47:W81–W87 [View Article] [PubMed]
    [Google Scholar]
  26. Navarro-Muñoz JC, Selem-Mojica N, Mullowney MW, Kautsar SA, Tryon JH et al. A computational framework to explore large-scale biosynthetic diversity. Nat Chem Biol 2020; 16:60–68 [View Article] [PubMed]
    [Google Scholar]
  27. Gilchrist CLM, Chooi Y-H. Clinker & clustermap.js: Automatic generation of gene cluster comparison figures. Bioinformatics 2021; 37:2473–2475 [View Article] [PubMed]
    [Google Scholar]
  28. Emms DM, Kelly S. OrthoFinder: phylogenetic orthology inference for comparative genomics. Genome Biol 2019; 20:238 [View Article] [PubMed]
    [Google Scholar]
  29. Emms DM, Kelly S. STAG: Species Tree inference from All Genes. Evol Biol 2018 [View Article]
    [Google Scholar]
  30. Jones P, Binns D, Chang H-Y, Fraser M, Li W et al. InterProScan 5: genome-scale protein function classification. Bioinformatics 2014; 30:1236–1240 [View Article] [PubMed]
    [Google Scholar]
  31. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 2014; 30:2114–2120 [View Article] [PubMed]
    [Google Scholar]
  32. Langmead B, Trapnell C, Pop M, Salzberg SL. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 2009; 10:R25 [View Article] [PubMed]
    [Google Scholar]
  33. Liao Y, Smyth GK, Shi W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 2014; 30:923–930 [View Article] [PubMed]
    [Google Scholar]
  34. R Core Team R: A Language and Environment for Statistical Computing Vienna, Austria: R Foundation for Statistical Computing; 2022
    [Google Scholar]
  35. Oksanen J, Kindt R, Legendre P, O’Hara B, Stevens MHH et al. The vegan package. Community ecology package 2007; 10:631–637
    [Google Scholar]
  36. Lenth RV. emmeans: Estimated Marginal Means, aka Least-Squares Means; 2022
  37. Fulde M, Willenborg J, Huber C, Hitzmann A, Willms D et al. The arginine-ornithine antiporter ArcD contributes to biological fitness of Streptococcus suis. Front Cell Infect Microbiol 2014; 4:107 [View Article] [PubMed]
    [Google Scholar]
  38. Fulde M, Willenborg J, de Greeff A, Benga L, Smith HE et al. ArgR is an essential local transcriptional regulator of the arcABC operon in Streptococcus suis and is crucial for biological fitness in an acidic environment. Microbiology 2011; 157:572–582 [View Article] [PubMed]
    [Google Scholar]
  39. Baums CG, Kaim U, Fulde M, Ramachandran G, Goethe R et al. Identification of a novel virulence determinant with serum opacification activity in Streptococcus suis. Infect Immun 2006; 74:6154–6162 [View Article] [PubMed]
    [Google Scholar]
  40. Takamatsu D, Osaki M, Tharavichitkul P, Takai S, Sekizaki T. Allelic variation and prevalence of serum opacity factor among the Streptococcus suis population. J Med Microbiol 2008; 57:488–494 [View Article] [PubMed]
    [Google Scholar]
  41. Courtney HS, Pownall HJ. The structure and function of serum opacity factor: a unique streptococcal virulence determinant that targets high-density lipoproteins. J Biomed Biotechnol 2010; 2010:956071 [View Article] [PubMed]
    [Google Scholar]
  42. Baig A, Weinert LA, Peters SE, Howell KJ, Chaudhuri RR et al. Whole genome investigation of a divergent clade of the pathogen Streptococcus suis. Front Microbiol 2015; 6:1191 [View Article] [PubMed]
    [Google Scholar]
  43. Atack JM, Tan A, Bakaletz LO, Jennings MP, Seib KL. Phasevarions of bacterial pathogens: methylomics sheds new light on old enemies. Trends Microbiol 2018; 26:715–726 [View Article] [PubMed]
    [Google Scholar]
  44. Segura M, Calzas C, Grenier D, Gottschalk M. Initial steps of the pathogenesis of the infection caused by Streptococcus suis: fighting against nonspecific defenses. FEBS Lett 2016; 590:3772–3799 [View Article] [PubMed]
    [Google Scholar]
  45. Van Calsteren M-R, Gagnon F, Lacouture S, Fittipaldi N, Gottschalk M. Structure determination of Streptococcus suis serotype 2 capsular polysaccharide. Biochem Cell Biol 2010; 88:513–525 [View Article] [PubMed]
    [Google Scholar]
  46. Okura M, Auger J-P, Shibahara T, Goyette-Desjardins G, Van Calsteren M-R et al. Capsular polysaccharide switching in Streptococcus suis modulates host cell interactions and virulence. Sci Rep 2021; 11:6513 [View Article] [PubMed]
    [Google Scholar]
  47. Smith HE, Damman M, van der Velde J, Wagenaar F, Wisselink HJ et al. Identification and characterization of the cps locus of Streptococcus suis serotype 2: the capsule protects against phagocytosis and is an important virulence factor. Infect Immun 1999; 67:1750–1756 [View Article] [PubMed]
    [Google Scholar]
  48. Wu K, Xu H, Zheng Y, Wang L, Zhang X et al. CpsR, a GntR family regulator, transcriptionally regulates capsular polysaccharide biosynthesis and governs bacterial virulence in Streptococcus pneumoniae. Sci Rep 2016; 6:29255 [View Article] [PubMed]
    [Google Scholar]
  49. Zhou Y, Nie R, Liu X, Kong J, Wang X et al. GntR is involved in the expression of virulence in strain Streptococcus suis P1/7. FEMS Microbiol Lett 2018; 365: [View Article] [PubMed]
    [Google Scholar]
  50. Shah P, Nanduri B, Swiatlo E, Ma Y, Pendarvis K. Polyamine biosynthesis and transport mechanisms are crucial for fitness and pathogenesis of Streptococcus pneumoniae. Microbiology 2011; 157:504–515 [View Article] [PubMed]
    [Google Scholar]
  51. Griswold AR, Jameson-Lee M, Burne RA. Regulation and physiologic significance of the agmatine deiminase system of Streptococcus mutans UA159. J Bacteriol 2006; 188:834–841 [View Article] [PubMed]
    [Google Scholar]
  52. Griswold AR, Chen Y-Y, Burne RA. Analysis of an agmatine deiminase gene cluster in Streptococcus mutans UA159. J Bacteriol 2004; 186:1902–1904 [View Article] [PubMed]
    [Google Scholar]
  53. Liu Y, Zeng L, Burne RA. AguR is required for induction of the Streptococcus mutans agmatine deiminase system by low pH and agmatine. Appl Environ Microbiol 2009; 75:2629–2637 [View Article] [PubMed]
    [Google Scholar]
  54. Gruening P, Fulde M, Valentin-Weigand P, Goethe R. Structure, regulation, and putative function of the arginine deiminase system of Streptococcus suis. J Bacteriol 2006; 188:361–369 [View Article] [PubMed]
    [Google Scholar]
  55. Johnston JW, Myers LE, Ochs MM, Benjamin WH, Briles DE et al. Lipoprotein PsaA in virulence of Streptococcus pneumoniae: surface accessibility and role in protection from superoxide. Infect Immun 2004; 72:5858–5867 [View Article] [PubMed]
    [Google Scholar]
  56. Lisher JP, Giedroc DP. Manganese acquisition and homeostasis at the host-pathogen interface. Front Cell Infect Microbiol 2013; 3:91 [View Article] [PubMed]
    [Google Scholar]
  57. Niven DF, Ekins A, al-Samaurai AA. Effects of iron and manganese availability on growth and production of superoxide dismutase by Streptococcus suis. Can J Microbiol 1999; 45:1027–1032 [View Article] [PubMed]
    [Google Scholar]
  58. Wichgers Schreur PJ, Rebel JMJ, Smits MA, van Putten JPM, Smith HE. TroA of Streptococcus suis is required for manganese acquisition and full virulence. J Bacteriol 2011; 193:5073–5080 [View Article] [PubMed]
    [Google Scholar]
  59. Zheng B, Zhang Q, Gao J, Han H, Li M et al. Insight into the interaction of metal ions with TroA from Streptococcus suis. PLoS One 2011; 6:e19510 [View Article] [PubMed]
    [Google Scholar]
  60. Peng W, Yang X, Wang N, Gao T, Liu Z et al. PerR-regulated manganese import contributes to oxidative stress defense in Streptococcus suis. Appl Environ Microbiol 2022; 88:e0008622 [View Article] [PubMed]
    [Google Scholar]
  61. Zhang T, Ding Y, Li T, Wan Y, Li W et al. A Fur-like protein PerR regulates two oxidative stress response related operons dpr and metQIN in Streptococcus suis. BMC Microbiol 2012; 12:85 [View Article] [PubMed]
    [Google Scholar]
  62. Peng W, Yang X, Wang Y, Wang N, Li X et al. Mn uptake system affects the virulence of Streptococcus suis by mediating oxidative stress. Vet Microbiol 2022; 272:109518 [View Article] [PubMed]
    [Google Scholar]
  63. Xu J, Zheng C, Cao M, Zeng T, Zhao X et al. The manganese efflux system MntE contributes to the virulence of Streptococcus suis serotype 2. Microb Pathog 2017; 110:23–30 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000992
Loading
/content/journal/mgen/10.1099/mgen.0.000992
Loading

Data & Media loading...

Supplements

Supplementary material 1

EXCEL

Supplementary material 2

EXCEL

Supplementary material 3

EXCEL

Supplementary material 4

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error