Review
Critical Streptococcus suis Virulence Factors: Are They All Really Critical?

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Streptococcus suis is a major swine pathogen – an emerging zoonotic agent whose pathogenesis of disease is partially characterized.

S. suis is an encapsulated microorganism and its capsular polysaccharide (CPS) allows bacterial evasion of the host immune system and bloodstream dissemination. But, the CPS is not the only virulence factor and, under certain circumstances, its absence may also be beneficial to pathogenic strains.

Indeed, the immune-pathogenesis of S. suis-induced disease is a complex, multifactorial process.

Yet, the discovery of a large array of virulence factors claimed as ‘critical’ for the pathogen's virulence has brought confusion into the field of S. suis.

The large genetic diversity of the S. suis species further complicated the study of the pathogenesis of the disease.

Streptococcus suis is an important swine pathogen that can be transmitted to humans by contact with diseased animals or contaminated raw pork products. This pathogen possesses a coat of capsular polysaccharide (CPS) that confers protection against the immune system. Yet, the CPS is not the only virulence factor enabling this bacterium to successfully colonize, invade, and disseminate in its host leading to severe systemic diseases such as meningitis and toxic shock-like syndrome. Indeed, recent research developments, cautiously inventoried in this review, have revealed over 100 ‘putative virulence factors or traits’ (surface-associated or secreted components, regulatory genes or metabolic pathways), of which at least 37 have been claimed as being ‘critical’ for virulence. In this review we discuss the current contradictions and controversies raised by this explosion of virulence factors and the future directions that may be conceived to advance and enlighten research on S. suis pathogenesis.

Section snippets

Understanding the Virulence of Streptococcus suis: An Emerging or Re-emerging Pathogen

The global willingness to reduce the preventative use of antibiotics in food-producing livestock in combination with the lack of effective vaccines has led to the re-emergence of animal bacterial pathogens with a high potential of zoonosis (see Glossary). This is the case of Streptococcus suis, a Gram-positive bacterium which causes meningitis, sepsis, and other diseases in swine. This infection not only results in severe economic losses and raises concerns on animal welfare, but the organism

Streptococcus suis: A Highly Diverse Species

The majority of porcine S. suis infections are caused by strains of a relatively small number of serotypes (Box 1). Albeit the distribution of serotypes from clinical cases differs depending on the geographic location (Box 1), serotype 2 strains are by far responsible for the majority of cases in both swine and humans worldwide, and thus have been historically considered the most frequent and virulent type [3]. Besides this serotype, recent years have seen the emergence of serotype 9 strains

Historical Issues with S. suis Virulence and Virulence Factor Identification

As mentioned above, and even though an important diversity among S. suis strains has been observed, most studies on virulence factors and the pathogenesis of the infection are based on archetypal serotype 2 strains, either virulent ST1 European strains or the clonal, epidemic ST7 Chinese strain. Figure 2 provides a simplified schematic view of the S. suis serotype 2 pathogenesis of infection (further described in Box 3). Only few studies have investigated a limited number of virulence traits in

The Controversy: Overabundance of Novel ‘Crucial' Virulence Factors

Bacterial virulence is ‘the ability to enter into, replicate within, and persist at host sites that are inaccessible to commensal species’ [57]. The last comprehensive review of the putative role of S. suis virulence factors was published in 2012 [26], and the list of factors potentially involved in the pathogenesis of S. suis-induced disease rapidly expanded since. Tables S1–S5 extensively summarize all proposed S. suis virulence factors based on mutagenesis studies. One feature of more recent

CPS Is Undisputedly Considered the Major Virulence Factor but…

S. suis survival in blood, and dissemination, depend on the production of a thick CPS which protects the bacterium against immune-recognition and immune-clearance [26]. Indeed, there is unanimity on published studies that used different in vitro and in vivo experiments with isogenic unencapsulated mutant strains, and all have conclusively shown that the absence of CPS correlates with highly increased phagocytosis and/or killing of these strains by phagocytic cells with a rapid clearance from

Concluding Remarks and Future Perspectives

Undoubtedly, S. suis is a very heterogonous species which complicates the characterization of virulence factors. Throughout the contradictions and controversies discussed in this review, the following issues deserve consideration in the study of virulence factor candidates (see Outstanding Questions):

  • 1.

    Need of confirmation of a critical role in virulence of those candidates by independent laboratories with well characterized and completely sequenced strains of different STs (and serotypes).

  • 2.

Acknowledgments

Results discussed in this review and carried out in our laboratories have been funded by the Natural Sciences and Engineering Research Council of Canada [grant #154280 to MG and 342150-07 to MS] and by China–Canada Joint Health Research Initiative financed by Canadian Institutes of Health Research and the National Natural Science Foundation of China (812111251). This publication made use of the multilocus sequence typing (MLST) website (http://www.mlst.net) at Imperial College, London,

Glossary

Clonal complex
a group of bacterial strains, derived from a common ancestor, which share many alleles at various phylogenetically informative loci. As such, the clonal complex usually includes the ancestral genotype and strains with minor variations. As this term has a broad meaning in epidemiology and may be defined by different typing methods, here, sequence types (STs) are grouped into clonal complexes by their similarity to a central allelic profile.
Multilocus sequence typing (MLST)
a

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