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

Segura, Mariela; Fittipaldi, Nahuel; Calzas, Cynthia; Gottschalk, Marcelo

doi:10.1016/j.tim.2017.02.005

Cited by 214 publications

(276 citation statements)

References 100 publications

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“…Based on the antigenicity of the capsular polysaccharide (CPS), more than 30 serotypes have been identified [1]. S. suis is also recognized as an important zoonotic pathogen for humans in close contact with infected pigs or contaminated pork.…”

Section: Introductionmentioning

confidence: 99%

Streptococcus suis synthesizes deoxyadenosine and adenosine by 5’-nucleotidase to dampen host immune responses

et al. 2018

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Streptococcus suis is a major porcine bacterial pathogen and emerging zoonotic agent. S. suis 5ʹ-nucleotidase is able to convert adenosine monophosphate to adenosine, resulting in inhibiting neutrophil functions in vitro and it is an important virulence factor. Here, we show that S. suis 5ʹ-nucleotidase not only enables producing 2ʹ-deoxyadenosine from 2ʹ-deoxyadenosine monophosphate by the enzymatic assay and reversed-phase high performance liquid chromatography (RP-HPLC) analysis in vitro, but also synthesizes both 2ʹ-deoxyadenosine and adenosine in mouse blood in vivo by RP-HPLC and liquid chromatography with tandem mass spectrometry analyses. Cellular cytotoxicity assay and Western blot analysis indicated that the production of 2ʹ-deoxyadenosine by 5ʹ-nucleotidase triggered the death of mouse macrophages RAW 264.7 in a caspase-3-dependent way. The in vivo infection experiment showed that 2ʹ-deoxyadenosine synthesized by 5ʹ-nucleotidase caused monocytopenia in mouse blood. The in vivo transcriptome analysis in mouse blood showed the inhibitory effect of 5ʹ-nucleotidase on neutrophil functions and immune responses probably mediated through the generation of adenosine. Taken together, these findings indicate that S. suis synthesizes 2ʹ-deoxyadenosine and adenosine by 5ʹ-nucleotidase to dampen host immune responses, which represents a new mechanism of S. suis pathogenesis.

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Section: Introductionmentioning

confidence: 99%

Streptococcus suis synthesizes deoxyadenosine and adenosine by 5’-nucleotidase to dampen host immune responses

et al. 2018

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“…We showed that most of the S. suis serotype 2 available genomes, including from different STs, possess genes encoding AgI/II. Interestingly, the gene was absent from the ST1 strain P1/7, which is commonly used as a reference for investigation of virulence [6]. We also identified AgI/II-encoding genes in the genome of the Chinese serotype 9 strain D12, in the serotype 9 reference strain 22083, as well as in a collection of 25 serotype 9 field strains (added herein given the limited number of serotype 9 genomes available), alongside a human isolate, tested by PCR.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly to other pathogens, S. suis is also able to bind ECM components, which have been suggested to be implicated as cell receptors [1]. At least 28 different S. suis components have been described to be involved in such interactions so far [1, 6]. In the present study, it was clearly shown that the AgI/II plays an important role in the adhesion of S. suis serotype 9 to collagen I, fibrinogen, and fibronectin.…”

Section: Discussionmentioning

confidence: 99%

“…The serotype 9 has recently emerged in certain European countries, such as Spain, the Netherlands, and Germany [4]. Yet, very few studies have addressed the presence of virulence factors in this serotype, and putative virulence factors described for serotype 2 strains may not always be present in serotype 9 strains [6]. Moreover, the first S. suis serotype 9 human case of infection was reported in 2015 [7].…”

Section: Introductionmentioning

confidence: 99%

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Serotype-specific role of antigen I/II in the initial steps of the pathogenesis of the infection caused by Streptococcus suis

Chuzeville

Auger

Dumesnil

et al. 2017

Vet Res

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Streptococcus suis is one of the most important post-weaning porcine bacterial pathogens worldwide. The serotypes 2 and 9 are often considered the most virulent and prevalent serotypes involved in swine infections, especially in Europe. However, knowledge of the bacterial factors involved in the first steps of the pathogenesis of the infection remains scarce. In several pathogenic streptococci, expression of multimodal adhesion proteins known as antigen I/II (AgI/II) have been linked with persistence in the upper respiratory tract and the oral cavity, as well as with bacterial dissemination. Herein, we report expression of these immunostimulatory factors by S. suis serotype 2 and 9 strains and that AgI/II-encoding genes are carried by integrative and conjugative elements. Using mutagenesis and different in vitro assays, we demonstrate that the contribution of AgI/II to the virulence of the serotype 2 strain used herein appears to be modest. In contrast, data demonstrate that the serotype 9 AgI/II participates in self-aggregation, induces salivary glycoprotein 340-related aggregation, contributes to biofilm formation and increased strain resistance to low pH, as well as in bacterial adhesion to extracellular matrix proteins and epithelial cells. Moreover, the use of a porcine infection model revealed that AgI/II contributes to colonization of the upper respiratory tract of pigs. Taken together, these findings suggest that surface exposed AgI/II likely play a key role in the first steps of the pathogenesis of the S. suis serotype 9 infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-017-0443-4) contains supplementary material, which is available to authorized users.

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“…However, special adaption to its main host, the pig, is not well understood. A myriad of virulence-associated factors involved in immune evasion have been described for S suis [6,7]. Virulence factors involved specifically in complement evasion on the other hand are scarce.…”

Section: Introductionmentioning

confidence: 99%

IgM cleavage by Streptococcus suis reduces IgM bound to the bacterial surface and is a novel complement evasion mechanism

et al. 2018

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Streptococcus suis (S. suis) causes meningitis, arthritis and endocarditis in piglets. The aim of this study was to characterize the IgM degrading enzyme of S. suis (IdeSsuis) and to investigate the role of IgM cleavage in evasion of the classical complement pathway and pathogenesis. Targeted mutagenesis of a cysteine in the putative active center of IdeSsuis abrogated IgM cleavage completely. In contrast to wt rIdeSsuis, point mutated rIdeSsuis_C195S did not reduce complement-mediated hemolysis indicating that complement inhibition by rIdeSsuis depends on the IgM proteolytic activity. A S. suis mutant expressing IdeSsuis_C195S did not reduce IgM labeling, whereas the wt and complemented mutant showed less IgM F(ab’)2 and IgM Fc antigen on the surface. IgM cleavage increased survival of S. suis in porcine blood ex vivo and mediated complement evasion as demonstrated by blood survival and C3 deposition assays including the comparative addition of rIdeSsuis and rIdeSsuis_C195S. However, experimental infection of piglets disclosed no significant differences in virulence between S. suis wt and isogenic mutants without IgM cleavage activity. This work revealed for the first time in vivo labeling of S. suis with IgM in the cerebrospinal fluid of piglets with meningitis. In conclusion, this study classifies IdeSsuis as a cysteine protease and emphasizes the role of IgM cleavage for bacterial survival in porcine blood and complement evasion though IgM cleavage is not crucial for the pathogenesis of serotype 2 meningitis.

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

Cited by 214 publications

References 100 publications

Streptococcus suis synthesizes deoxyadenosine and adenosine by 5’-nucleotidase to dampen host immune responses

Streptococcus suis synthesizes deoxyadenosine and adenosine by 5’-nucleotidase to dampen host immune responses

Serotype-specific role of antigen I/II in the initial steps of the pathogenesis of the infection caused by Streptococcus suis

IgM cleavage by Streptococcus suis reduces IgM bound to the bacterial surface and is a novel complement evasion mechanism

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