Streptococcus suis is a swine pathogen and a zoonotic agent afflicting people in close contact with infected pigs or pork meat. Sporadic cases of human infections have been reported worldwide. In addition, S. suis outbreaks emerged in Asia, making this bacterium a primary health concern in this part of the globe. In pigs, S. suis disease results in decreased performance and increased mortality, which have a significant economic impact on swine production worldwide. Facing the new regulations in preventive use of antimicrobials in livestock and lack of effective vaccines, control of S. suis infections is worrisome. Increasing and sharing of knowledge on this pathogen is of utmost importance. As such, the pathogenesis and epidemiology of the infection, antimicrobial resistance, progress on diagnosis, prevention, and control were among the topics discussed during the 4th International Workshop on Streptococcus suis (held in Montreal, Canada, June 2019). This review gathers together recent findings on this important pathogen from lectures performed by lead researchers from several countries including Australia, Canada, France, Germany, Japan, Spain, Thailand, The Netherlands, UK, and USA. Finally, policies and recommendations for the manufacture, quality control, and use of inactivated autogenous vaccines are addressed to advance this important field in veterinary medicine.

Here we show that S. suis, a major bacterial pathogen of pigs and emerging pathogen in humans responds to a peptide pheromone by developing competence for DNA transformation. This species does not fall within any of the phylogenetic clusters of streptococci previously shown to regulate competence via peptide pheromones suggesting that more species of streptococci may be naturally competent. Induction of competence was dependent on ComX, a sigma factor that controls the streptococcal late competence regulon, extracellular addition of a comX-inducing peptide (XIP), and ComR, a regulator of comX. XIP was identified as an N-terminally truncated variant of ComS. Different comS alleles are present among strains of S. suis. These comS alleles are not functionally equivalent and appear to operate in conjuction with a cognate ComR to regulate comX through a conserved comR-box promoter. We demonstrate that these ‘pherotypes’ can be genetically transferred between strains, suggesting that similar approaches might be used to control competence induction in other lactic acid bacteria that lack ComR/ComS homologues but possess comX and the late competence regulon. The approaches described in this paper to identify and optimize peptide-induced competence may also assist other researchers wishing to identify natural competence in other bacteria. Harnessing natural competence is expected to accelerate genetic research on this and other important streptococcal pathogens and to allow high-throughput mutation approaches to be implemented, opening up new avenues for research.

ArgR is an essential local transcriptional regulator of the arcABC operon in Streptococcus suis and is crucial for biological fitness in an acidic environment Streptococcus suis is one of the most important pathogens in pigs and can also cause severe infections in humans. Despite its clinical relevance, very little is known about the factors that contribute to its virulence. Recently, we identified a new putative virulence factor in S. suis, the arginine deiminase system (ADS), an arginine catabolic enzyme system encoded by the arcABC operon, which enables S. suis to survive in an acidic environment. In this study, we focused on ArgR, an ADS-associated regulator belonging to the ArgR/AhrC arginine repressor family. Using an argR knockout strain we were able to show that ArgR is essential for arcABC operon expression and necessary for the biological fitness of S. suis. By cDNA expression microarray analyses and quantitative real-time RT-PCR we found that the arcABC operon is the only gene cluster regulated by ArgR, which is in contrast to the situation in many other bacteria. Reporter gene analysis with gfp under the control of the arcABC promoter demonstrated that ArgR is able to activate the arcABC promoter. Electrophoretic mobility shift assays with fragments of the arcABC promoter and recombinant ArgR, and chromatin immunoprecipitation with antibodies directed against ArgR, revealed that ArgR interacts with the arcABC promoter in vitro and in vivo by binding to a region from "147 to "72 bp upstream of the transcriptional start point. Overall, our results show that in S. suis, ArgR is an essential, system-specific transcriptional regulator of the ADS that interacts directly with the arcABC promoter in vivo. INTRODUCTIONThe regulation of arginine metabolism is mediated by the members of the ArgR/AhrC family of transcriptional regulators. These regulators and their cognate target sites are highly conserved among very diverse organisms, including Gram-positive and Gram-negative bacteria. In general, ArgR/AhrC proteins regulate their target genes by binding to operator sites, leading to repression of arginine biosynthetic genes and activation of catabolic genes in the presence of arginine (Gardan et al., 1995;Grandori et al., 1995;Kiupakis & Reitzer, 2002;Klingel et al., 1995;Lu & Abdelal, 1999;Makarova et al., 2001). Furthermore, it is now clear that in Escherichia coli, ArgR not only is involved in regulation of arginine metabolism but also regulates various genes of arginine transport (Caldara et al., 2006).Mechanisms for arginine catabolism differ among organisms (Blakemore & Canale-Parola, 1976;Broman et al., 1978;Floderus et al., 1990;Mercenier et al., 1980). A widely distributed system in many bacteria, including homofermentative cocci, is the arginine deiminase system (ADS). It allows degradation of arginine into ornithine, ammonia and carbon dioxide catalysed by arginine deiminase (ArcA), ornithine carbamoyltransferase (ArcB) and carbamate kinase (ArcC) (Barcelona-Andrés et al., 2002;Burne et al., 1989; C...

In the present study we investigated the role of the fibronectin (FN)-and fibrinogen (FGN)-binding protein (FBPS) in the pathogenesis of Streptococcus suis serotype 2 in piglets. The complete gene encoding FBPS from S. suis serotype 2 was cloned in Escherichia coli and sequenced. The occurrence of the gene in various serotypes was analyzed by hybridization studies. The FBPS protein was expressed in E. coli and purified, and binding to human FN and FGN was demonstrated. The induction of antibodies in piglets was studied upon infection. An isogenic mutant unable to produce FBPS was constructed, and the levels of virulence of the wild-type and mutant strains were compared in a competitive infection model in young piglets. Organ cultures showed that FBPS was not required for colonization of the tonsils but that FBPS played a role in the colonization of the specific organs involved in an S. suis infection. Therefore, the FBPS mutant was considered as an attenuated mutant.Streptococcus suis causes severe infections in piglets. The bacterial infections include meningitis, septicemia, and arthritis, and the animals often do not survive the infection (6, 28). Occasionally, S. suis causes septicemia and meningitis in humans (3). The pathogenesis of an S. suis infection is rarely understood. Sows are symptomless carriers of S. suis on their tonsils and pass the bacteria on to their piglets. The piglets cannot cope with the bacterium and subsequently develop the specific symptoms of an S. suis infection. Until now, 35 capsular serotypes of S. suis have been described (26), but serotype 2 strains are most often isolated from diseased piglets. Capsule is an important virulence factor, since piglets infected with an acapsular mutant of S. suis serotype 2 strains do not develop any clinical symptoms (22). Bacterial proteins have been suggested to play a role in the pathogenesis as well (1,26). The expression of muramidase-released protein (MRP), extracellular factor (EF), and suilysin was shown to be strongly associated with pathogenic strains of S. suis serotype 2 (2, 29, 30). Since isogenic mutants lacking MRP and EF and isogenic mutants lacking suilysin were still pathogenic for young piglets, these proteins are not absolutely required for virulence (1,23). Recently, a new virulence factor was identified (21) by using a complementation approach. The function of this virulence factor in the pathogenesis has to be further investigated.Many important virulence factors are environmentally regulated and are induced at specific stages of the infection process (15). To identify these genes in S. suis, we cloned promoters and their downstream sequences that are "on" during experimental S. suis infection of piglets (20). Twenty-two in vivo-selected (ivs) genes were found. Two of the ivs genes were directly linked to virulence, since homology to genes in the database that encode for known virulence factors was found. One of these ivs genes (ivs-21) was identical to the epf gene of virulent S. suis serotype 2 strains (30). The other (i...