JGI Streptococcus suis 89/1591 Home

Streptococcus suis is a Gram-positive, facultatively anaerobe coccus, possessing cell wall antigenic determinants related to Lancefield group D, although it is genetically unrelated to other members of this group. The original classification of S. suis into Lancefield groups R, S and T, which actually correspond to serotypes 2, 1 and 15, respectively⁶, is obsolete and should be avoided. During the last years, 26 new capsular types or serotypes have been described, reaching a total of 35 serotypes in 1995¹¹. Of them, serotype 2 is the most frequent serotype recovered from diseased pigs¹⁰.This serotype is also the cause of serious infections in humans, especially in people in close contact with swine or pork products⁴. Human cases have been reported in The Netherlands, Denmark, Italy, Germany, Belgium, United Kingdom, France, Spain, Sweden, Ireland, Austria, Hungary, Hong Kong, Croatia, Japan, Singapore, Taiwan, New Zealand, and Argentina. Mysteriously, only few cases have been reported in Canada and none in USA. This is probably the consequence of a serious diagnostic problem in laboratories working with human medicine. In fact, most of these laboratories would probably misidentify an isolate of S. suis⁴.

Serious disease in pigs caused by S. suis have been reported in all countries where the swine industry is important. The natural habitat of S. suis is the upper respiratory tract, particularly the tonsils and nasal cavities, and the genital and alimentary tracts of pigs¹⁰. This bacterium has been increasingly isolated from a wide range of mammalian species (including human beings) and from birds, which suggests new concepts about some epidemiological aspects of the infection. In pigs, the most important clinical feature associated with S. suis is meningitis. However, other pathologies have also been described, such as arthritis, endocarditis, pneumonia, and septicaemia with sudden death¹⁰. It is considered one of the most important bacterial pathogens that affect the swine industry.

Knowledge on the virulence factors of S. suis is still limited. Most studies have been carried out with serotype 2 strains. Although there is confusion in the description of virulence, researchers agree at least on one point: the existence of virulent and non virulent strains of S. suis serotype 2⁷. The capsule polysaccharide (CPS) is the only proven critical virulence factor since unencapsulated isogenic mutants were shown to be completely avirulent and rapidly cleared from circulation in pig and mouse models of infection^{1, 19}. However, the presence of capsulated non virulent strains is frequently reported⁷. Other factors, such as cell-associated or extracellular proteins (muramidase-released protein or MRP, extracellular factor or EF and suilysin), have also been proposed as putative virulence factors/markers⁷. However, isogenic mutants lacking these factors presented a similar level of virulence that their respective wild type strains^{12, 20}. In addition, European but not North American virulent strains seem to possess these proteins⁵. These two groups of strains are also genotypically different². Other putative virulence factors, including adhesins, proteolytic enzymes, bacteriocins and fimbriae have also been proposed¹⁵.

The pathogenesis of S. suis infections is poorly understood. Piglets are contaminated during farrowing (vertical transmission of the infection). They also diversely and probably heterogeneously acquire the bacterium due to close contact with the sows, her faeces, and the surrounding structures (pen walls, dirty soil, etc.). Reasons that may explain why S. suis will successfully colonise only some piglets and not others are poorly known. Infection of newborn piglets may also take place through the respiratory route from sow to piglets and among piglets. Colonised animals will harbour the bacteria in their tonsils. Some animals will only be healthy carriers and will never develop disease, whereas others will, sooner or later, develop bacteremia, sometimes septicaemia and, meningitis. Hence, in these cases, bacteria should travel throughout the bloodstream (as free bacteria and/or in close contact with monocytes) and reach the central nervous system (CNS), where it causes inflammation and damage responsible for the signs of meningitis⁷.

Presently, there are more than 400 DNA sequence entries that are currently listed in GenBank. Among them, genes coding for polysaccharide production and capsule transport¹⁹, iron-restricted factors¹⁷, the suilysin⁸, virulence-associated proteins²⁰, different enzymes^{3, 13}, IgG binding proteins¹⁶, and also in vivo-expressed genes¹⁸. Techniques for gene transfer and mutagenesis have been developed^{21, 23, 24}. The presence of plasmids and a phage have also been reported^{9, 22}. Strain 89-1591 of S. suis serotype 2 was isolated from a diseased pig and showed to be virulent in an experimental infection model¹⁴. This is an interesting strain, since it represents a typical North American virulent strain that lacks the above mentioned virulence protein markers (MRP, EF and suilysin). Genome sequencing of S. suis strain 89-1591 will contribute to reveal important information since no critical virulence factor (other than the capsule polysaccharide) has been described for this representative North America strain. A complete sequence of the genome of this strain will help to pursue studies on the interaction of this pathogen with host cells which may lead to the understanding of mechanisms of disease progression. This would contribute to develop potential therapies and preventive measures to control S. suis infections.

References
1. Charland, N., J. Harel, M. Kobisch, S. Lacasse and M. Gottschalk. 1998. Streptococcus suis serotype 2 mutants deficient in capsular expression. Microbiology. 144: 325-332.
2. Chatellier, S., M. Gottschalk, R. Higgins, R. Brousseau and J. Harel. 1999. Relatedness of Streptococcus suis serotype 2 isolates from different geographical origins as evaluated by molecular fingerprinting and phenotyping. J. Clin. Microbiol. 37 : 362-366.
3. Fontaine, M.C., J. Perez-Casal and P.J. Willson. 2004. Investigation of a novel DNase of Streptococcus suis serotype 2. Infect Immun. 72:774-781.
4. Gottschalk, M. 2004. Porcine Streptococcus suis strains as potential sources of infection in humans: an underdiagnosed problem in North America? J. Swine Health Prod. 12: 197-199.
5. Gottschalk, M., A. Lebrun, H. Wisselink, D. Dubreuil, H. Smith and U. Vecht 1998. Production of virulence-related proteins by Canadian strains of Streptococcus suis capsular type 2. Can. J. Vet. Res. 62 : 75-79
6. Gottschalk, M., R. Higgins, M. Jacques, K.R. Mittal, and J. Henrichsen. 1989. Description of 14 new capsular types of Streptococcus suis. J. Clin. Microbiol. 27 : 2633-2636.
7. Gottschalk, M. and M. Segura M. 2000. The pathogenesis of the meningitis caused by Streptococcus suis: the unresolved questions. Vet Microbiol. 76:259-272.
8. Jacobs, A.A., P. L. Loeffen, A. J. van den Berg and P. K. Storm. 1994. Identification, purification, and characterization of a thiol-activated hemolysin (suilysin) of Streptococcus suis. Infect Immun. 62:1742-1748.
9. Harel, J., G. Martinez, A. Nassar, H. Dezfulian, S. J. Labrie, R. Brousseau, S. Moineau and M. Gottschalk. 2003. Identification of an inducible bacteriophage in a virulent strain of Streptococcus suis serotype 2. Infect Immun. 71:6104-6108.
10. Higgins, R. and M. Gottschalk. 1999. Streptococcal diseases. In: Straw, B.E., D’Allaire, S., Mengeling, W.L., Taylor, D.J. (Eds), Diseases of Swine, Iowa State University Press, Ames, pp. 563-570.
11. Higgins, R., M. Gottschalk, M. Boudreau, A. Lebrun, and J. Henrichsen. 1995. Description of six new Streptococcus suis capsular types. J. Vet. Diagn. Invest. 7 : 405-406.
12. Lun, S., J. Perez-Casal, W. Connor, P. J. Willson. 2003. Role of suilysin in pathogenesis of Streptococcus suis capsular serotype 2. Microb Pathog. 34:27-37.
13. Osaki, M., D. Takamatsu, Y. Shimoji and T. Sekizaki. 2002. Characterization of Streptococcus suis genes encoding proteins homologous to sortase of gram-positive bacteria. J Bacteriol. 184:971-982.
14. Quessy, S., J.D. Dubreuil, M. Caya and R. Higgins. 1995. Discrimination of virulent and avirulent Streptococcus suis capsular type 2 isolates from different geographical origins. Infect Immun. 63:1975-1979.
15. Segura, M. and M. Gottschalk. 2004. Extracellular virulence factors of streptococci associated with animal diseases. Frontiers in Bioscience. 9:1157-1188.
16. Serhir, B., D. Dubreuil, R. Higgins and M. Jacques. 1995. Purification and characterization of a 52-kilodalton immunoglobulin G-binding protein from Streptococcus suis capsular type 2. J Bacteriol. 177:3830-3836.
17. Smith, H.E., H. Buijs, R. de Vries, H. J. Wisselink, N. Stockhofe-Zurwieden and M. A. Smits. 2001. Environmentally regulated genes of Streptococcus suis: identification by the use of iron-restricted conditions in vitro and by experimental infection of piglets. Microbiology. 147:271-280.
18. Smith, H.E., H. Buijs, H. J. Wisselink, N. Stockhofe-Zurwieden and M. A. Smits. 2001. Selection of virulence-associated determinants of Streptococcus suis serotype 2
by in vivo complementation Infect Immun. 69:1961-1966.
19. Smith, H.E., M. Damman, J. van der Velde, F. Wagenaar, H.J. Wisselink, N. Stockhofe-Zurwieden, and M. A. Smits, 1999. 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. 67, 1750-1756.
20. Smith, H.E., H.J. Wisselink, N. Stockhofe-Zurwieden, U. Vecht and M. A. Smits, M.A. 1997. Virulence markers of Streptococcus suis type 1 and 2. Adv. Exp. Med. Biol. 418, 651-656.
21. Smith, H.E., H. J. Wisselink, U. Vecht, A. L. Gielkens and M. A. Smits. 1995. High-efficiency transformation and gene inactivation in Streptococcus suis type
2. Microbiology. 141:181-188.
22. Stuart, J.G., E. J. Zimmerer and R. L. Maddux. 1992. Conjugation of antibiotic resistance in Streptococcus suis. Vet Microbiol. 30:213-222.
23. Takamatsu, D., M. Osaki and T. Sekizaki. 2001. Construction and characterization of Streptococcus suis-Escherichia coli shuttle cloning vectors. Plasmid. 45:101-113.
24. Takamatsu, D., M. Osaki, T. Sekizaki. 2001. Thermosensitive suicide vectors for gene replacement in Streptococcus suis. Plasmid. 46:140-148.

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