27 results on '"Marcelo Gottschalk"'
Search Results
2. Interactions of Streptococcus suis serotype 9 with host cells and role of the capsular polysaccharide: Comparison with serotypes 2 and 14.
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Jean-Philippe Auger, Servane Payen, David Roy, Audrey Dumesnil, Mariela Segura, and Marcelo Gottschalk
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Medicine ,Science - Abstract
Streptococcus suis is an important porcine bacterial pathogen and a zoonotic agent responsible for sudden death, septic shock and meningitis, of which serotype 2 is the most widespread, with serotype 14 also causing infections in humans in South-East Asia. Knowledge of its pathogenesis and virulence are almost exclusively based on these two serotypes. Though serotype 9 is responsible for the greatest number of porcine cases in Spain, the Netherlands and Germany, very little information is currently available regarding this serotype. Of the different virulence factors, the capsular polysaccharide (CPS) is required for S. suis virulence as it promotes resistance to phagocytosis and killing and masks surface components responsible for host cell activation. However, these roles have been described for serotypes 2 and 14, whose CPSs are structurally and compositionally similar, both containing sialic acid. Consequently, we evaluated herein the interactions of serotype 9 with host cells and the role of its CPS, which greatly differs from those of serotypes 2 and 14. Results demonstrated that serotype 9 adhesion to but not invasion of respiratory epithelial cells was greater than that of serotypes 2 and 14. Furthermore serotype 9 was more internalized by macrophages but equally resistant to whole blood killing. Though recognition of serotypes 2, 9 and 14 by DCs required MyD88-dependent signaling, in vitro pro-inflammatory mediator production induced by serotype 9 was much lower. In vivo, however, serotype 9 causes an exacerbated inflammatory response, which combined with persistent bacterial presence, is probably responsible for host death during the systemic infection. Though presence of the serotype 9 CPS masks surface components less efficiently than those of serotypes 2 and 14, the serotype 9 CPS remains critical for virulence as it is required for survival in blood and development of clinical disease, and this regardless of its unique composition and structure.
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- 2019
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3. Role of the Streptococcus suis serotype 2 capsular polysaccharide in the interactions with dendritic cells is strain-dependent but remains critical for virulence.
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Jean-Philippe Auger, Dominic Dolbec, David Roy, Mariela Segura, and Marcelo Gottschalk
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Medicine ,Science - Abstract
Streptococcus suis serotype 2 is an important porcine bacterial pathogen and zoonotic agent responsible for sudden death, septic shock, and meningitis. However, serotype 2 strains are heterogeneous, composed of a multitude of sequence types (STs) whose distribution greatly varies worldwide. Of the virulence factors presently described for S. suis, the capsular polysaccharide (CPS) is a critical factor implicated in a multitude of functions, including in impairment of phagocytosis and innate immune cell activation by masking underlying bacterial components. However, these roles have been described using Eurasian ST1 and ST7 strains, which greatly differ from North American ST25 strains. Consequently, the capacity of the CPS to mask surface antigens and putative virulence factors in non-Eurasian strains remains unknown. Herein, the role of the S. suis serotype 2 CPS of a prototype intermediate virulent North American ST25 strain, in comparison with that of a virulent European ST1 strain, with regards to interactions with dendritic cells, as well as virulence during the systemic phase of infection, was evaluated. Results demonstrated that the CPS remains critical for virulence and development of clinical disease regardless of strain background, due to its requirement for survival in blood. However, its role in the interactions with dendritic cells is strain-dependent. Consequently, certain key characteristics associated with the CPS are not necessarily applicable to all S. suis serotype 2 strains. This indicates that though certain factors may be important for S. suis serotype 2 virulence, strain background could be as determining, reiterating the need in using strains from varying backgrounds in order to better characterize the S. suis pathogenesis.
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- 2018
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4. The bias of experimental design, including strain background, in the determination of critical Streptococcus suis serotype 2 virulence factors.
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Jean-Philippe Auger, Sarah Chuzeville, David Roy, Annabelle Mathieu-Denoncourt, Jianguo Xu, Daniel Grenier, and Marcelo Gottschalk
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Medicine ,Science - Abstract
Streptococcus suis serotype 2 is an important porcine bacterial pathogen and emerging zoonotic agent mainly responsible for sudden death, septic shock, and meningitis. However, serotype 2 strains are genotypically and phenotypically heterogeneous. Though a multitude of virulence factors have been described for S. suis serotype 2, the lack of a clear definition regarding which ones are truly "critical" has created inconsistencies that have only recently been highlighted. Herein, the involvement of two factors previously described as being critical for S. suis serotype 2 virulence, whether the dipeptidyl peptidase IV and autolysin, were evaluated with regards to different ascribed functions using prototype strains belonging to important sequence types. Results demonstrate a lack of reproducibility with previously published data. In fact, the role of the dipeptidyl peptidase IV and autolysin as critical virulence factors could not be confirmed. Though certain in vitro functions may be ascribed to these factors, their roles are not unique for S. suis, probably due to compensation by other factors. As such, variations and discrepancies in experimental design, including in vitro assays, cell lines, and animal models, are an important source of differences between results. Moreover, the use of different sequence types in this study demonstrates that the role attributed to a virulence factor may vary according to the S. suis serotype 2 strain background. Consequently, it is necessary to establish standard experimental designs according to the experiment and purpose in order to facilitate comparison between laboratories. Alongside, studies should include strains of diverse origins in order to prevent erroneous and biased conclusions that could affect future studies.
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- 2017
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5. Transcriptional Analysis of PRRSV-Infected Porcine Dendritic Cell Response to Streptococcus suis Infection Reveals Up-Regulation of Inflammatory-Related Genes Expression.
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Gaël Auray, Claude Lachance, Yingchao Wang, Carl A Gagnon, Mariela Segura, and Marcelo Gottschalk
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Medicine ,Science - Abstract
The porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important swine pathogens and often serves as an entry door for other viral or bacterial pathogens, of which Streptococcus suis is one of the most common. Pre-infection with PRRSV leads to exacerbated disease caused by S. suis infection. Very few studies have assessed the immunological mechanisms underlying this higher susceptibility. Since antigen presenting cells play a major role in the initiation of the immune response, the in vitro transcriptional response of bone marrow-derived dendritic cells (BMDCs) and monocytes in the context of PRRSV and S. suis co-infection was investigated. BMDCs were found to be more permissive than monocytes to PRRSV infection; S. suis phagocytosis by PRRSV-infected BMDCs was found to be impaired, whereas no effect was found on bacterial intracellular survival. Transcription profile analysis, with a major focus on inflammatory genes, following S. suis infection, with and without pre-infection with PRRSV, was then performed. While PRRSV pre-infection had little effect on monocytes response to S. suis infection, a significant expression of several pro-inflammatory molecules was observed in BMDCs pre-infected with PRRSV after a subsequent infection with S. suis. While an additive effect could be observed for CCL4, CCL14, CCL20, and IL-15, a distinct synergistic up-regulatory effect was observed for IL-6, CCL5 and TNF-α after co-infection. This increased pro-inflammatory response by DCs could participate in the exacerbation of the disease observed during PRRSV and S. suis co-infection.
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- 2016
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6. Population Structure and Antimicrobial Resistance Profiles of Streptococcus suis Serotype 2 Sequence Type 25 Strains.
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Taryn B T Athey, Sarah Teatero, Daisuke Takamatsu, Jessica Wasserscheid, Ken Dewar, Marcelo Gottschalk, and Nahuel Fittipaldi
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Medicine ,Science - Abstract
Strains of serotype 2 Streptococcus suis are responsible for swine and human infections. Different serotype 2 genetic backgrounds have been defined using multilocus sequence typing (MLST). However, little is known about the genetic diversity within each MLST sequence type (ST). Here, we used whole-genome sequencing to test the hypothesis that S. suis serotype 2 strains of the ST25 lineage are genetically heterogeneous. We evaluated 51 serotype 2 ST25 S. suis strains isolated from diseased pigs and humans in Canada, the United States of America, and Thailand. Whole-genome sequencing revealed numerous large-scale rearrangements in the ST25 genome, compared to the genomes of ST1 and ST28 S. suis strains, which result, among other changes, in disruption of a pilus island locus. We report that recombination and lateral gene transfer contribute to ST25 genetic diversity. Phylogenetic analysis identified two main and distinct Thai and North American clades grouping most strains investigated. These clades also possessed distinct patterns of antimicrobial resistance genes, which correlated with acquisition of different integrative and conjugative elements (ICEs). Some of these ICEs were found to be integrated at a recombination hot spot, previously identified as the site of integration of the 89K pathogenicity island in serotype 2 ST7 S. suis strains. Our results highlight the limitations of MLST for phylogenetic analysis of S. suis, and the importance of lateral gene transfer and recombination as drivers of diversity in this swine pathogen and zoonotic agent.
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- 2016
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7. Complex Population Structure and Virulence Differences among Serotype 2 Streptococcus suis Strains Belonging to Sequence Type 28.
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Taryn B T Athey, Jean-Philippe Auger, Sarah Teatero, Audrey Dumesnil, Daisuke Takamatsu, Jessica Wasserscheid, Ken Dewar, Marcelo Gottschalk, and Nahuel Fittipaldi
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Medicine ,Science - Abstract
Streptococcus suis is a major swine pathogen and a zoonotic agent. Serotype 2 strains are the most frequently associated with disease. However, not all serotype 2 lineages are considered virulent. Indeed, sequence type (ST) 28 serotype 2 S. suis strains have been described as a homogeneous group of low virulence. However, ST28 strains are often isolated from diseased swine in some countries, and at least four human ST28 cases have been reported. Here, we used whole-genome sequencing and animal infection models to test the hypothesis that the ST28 lineage comprises strains of different genetic backgrounds and different virulence. We used 50 S. suis ST28 strains isolated in Canada, the United States and Japan from diseased pigs, and one ST28 strain from a human case isolated in Thailand. We report a complex population structure among the 51 ST28 strains. Diversity resulted from variable gene content, recombination events and numerous genome-wide polymorphisms not attributable to recombination. Phylogenetic analysis using core genome single-nucleotide polymorphisms revealed four discrete clades with strong geographic structure, and a fifth clade formed by US, Thai and Japanese strains. When tested in experimental animal models, strains from this latter clade were significantly more virulent than a Canadian ST28 reference strain, and a closely related Canadian strain. Our results highlight the limitations of MLST for both phylogenetic analysis and virulence prediction and raise concerns about the possible emergence of ST28 strains in human clinical cases.
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- 2015
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8. Suicin 3908, a new lantibiotic produced by a strain of Streptococcus suis serotype 2 isolated from a healthy carrier pig.
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Katy Vaillancourt, Geneviève LeBel, Michel Frenette, Marcelo Gottschalk, and Daniel Grenier
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Medicine ,Science - Abstract
While Streptococcus suis serotype 2 is known to cause severe infections in pigs, it can also be isolated from the tonsils of healthy animals that do not develop infections. We hypothesized that S. suis strains in healthy carrier pigs may have the ability to produce bacteriocins, which may contribute to preventing infections by pathogenic S. suis strains. Two of ten S. suis serotype 2 strains isolated from healthy carrier pigs exhibited antibacterial activity against pathogenic S. suis isolates. The bacteriocin produced by S. suis 3908 was purified to homogeneity using a three-step procedure: ammonium sulfate precipitation, cationic exchange HPLC, and reversed-phase HPLC. The bacteriocin, called suicin 3908, had a low molecular mass; was resistant to heat, pH, and protease treatments; and possessed membrane permeabilization activity. Additive effects were obtained when suicin 3908 was used in combination with penicillin G or amoxicillin. The amino acid sequence of suicin 3908 suggested that it is lantibiotic-related and made it possible to identify a bacteriocin locus in the genome of S. suis D12. The putative gene cluster involved in suicin production by S. suis 3908 was amplified by PCR, and the sequence analysis revealed the presence of nine open reading frames (ORFs), including the structural gene and those required for the modification of amino acids, export, regulation, and immunity. Suicin 3908, which is encoded by the suiA gene, exhibited approximately 50% identity with bovicin HJ50 (Streptococcus bovis), thermophilin 1277 (Streptococcus thermophilus), and macedovicin (Streptococcus macedonicus). Given that S. suis 3908 cannot cause infections in animal models, that it is susceptible to conventional antibiotics, and that it produces a bacteriocin with antibacterial activity against all pathogenic S. suis strains tested, it could potentially be used to prevent infections and to reduce antibiotic use by the swine industry.
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- 2015
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9. Purification and Characterization of Suicin 65, a Novel Class I Type B Lantibiotic Produced by Streptococcus suis.
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Katy Vaillancourt, Geneviève LeBel, Michel Frenette, Nahuel Fittipaldi, Marcelo Gottschalk, and Daniel Grenier
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Medicine ,Science - Abstract
Bacteriocins are antimicrobial peptides of bacterial origin that are considered as a promising alternative to the use of conventional antibiotics. Recently, our laboratory reported the purification and characterization of two lantibiotics, suicin 90-1330 and suicin 3908, produced by the swine pathogen and zoonotic agent Streptococcus suis (serotype 2). In this study, a novel bacteriocin produced by S. suis has been identified and characterized. The producing strain S. suis 65 (serotype 2) was found to belong to the sequence type 28, that includes strains known to be weakly or avirulent in a mouse model. The bacteriocin, whose production was only possible following growth on solid culture medium, was purified to homogeneity by cationic exchange and reversed-phase high-pressure liquid chromatography. The bacteriocin, named suicin 65, was heat, pH and protease resistant. Suicin 65 was active against all S. suis isolates tested, including antibiotic resistant strains. Amino acid sequencing of the purified bacteriocin by Edman degradation revealed the presence of modified amino acids suggesting a lantibiotic. Using the partial sequence obtained, a blast was performed against published genomes of S. suis and allowed to identify a putative lantibiotic locus in the genome of S. suis 89-1591. From this genome, primers were designed and the gene cluster involved in the production of suicin 65 by S. suis 65 was amplified by PCR. Sequence analysis revealed the presence of ten open reading frames, including a duplicate of the structural gene. The structural genes (sssA and sssA') of suicin 65 encodes a 25-amino acid residue leader peptide and a 26-amino acid residue mature peptide yielding an active bacteriocin with a deducted molecular mass of 3,005 Da. Mature suicin 65 showed a high degree of identity with class I type B lantibiotics (globular structure) produced by Streptococcus pyogenes (streptococcin FF22; 84.6%), Streptococcus macedonicus (macedocin ACA-DC 198; 84.6%), and Lactococcus lactis subsp. lactis (lacticin 481; 74.1%). Further studies will evaluate the ability of suicin 65 or the producing strain to prevent experimental S. suis infections in pigs.
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- 2015
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10. Comparative genomic hybridization identifies virulence differences in Streptococcus suis.
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Han Zheng, Ruiting Lan, Xiao Zheng, Zhigang Cui, Zhijie Liu, Xuemei Bai, Shaobo Ji, Marcelo Gottschalk, and Jianguo Xu
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Medicine ,Science - Abstract
Streptococcus suis is an important zoonotic pathogen. However, identification of virulent S. suis strains is complicated because of the high diversity of the species. Here we evaluated the genetic difference among S. suis strains using comparative genomic hybridization (CGH) and virulence variation in vivo and in vitro. We showed that different clades differed in their ability to activate TLR2/6 in vitro and their capacity to induce cytokine production in vivo as well as their resistance to phagocytosis and survival in vivo. Our data showed the S. suis strains tested can be classified into three groups having differing levels of virulence: epidemic and highly virulent strains were clustered into clade Ia (epidemic and highly virulent group, E/HV group), virulent strains were clustered into clade Ib (virulent group, V group), and intermediately or weakly virulent strains were clustered into other clades (intermediately or weakly virulent group, I/WV group). Our study provided further insight into the genomic and virulence variation of S. suis.
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- 2014
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11. Development of multiplex PCR assays for the identification of the 33 serotypes of Streptococcus suis.
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Zhijie Liu, Han Zheng, Marcelo Gottschalk, Xuemei Bai, Ruiting Lan, Shaobo Ji, Haican Liu, and Jianguo Xu
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Medicine ,Science - Abstract
Streptococcussuis is an important zoonotic agent causing severe diseases in pigs and humans. To date, 33 serotypes of S. suis have been identified based on antigenic differences in the capsular polysaccharide. The capsular polysaccharide synthesis (cps) locus encodes proteins/enzymes that are responsible for capsular production and variation in the capsule structures are the basis of S. suis serotyping. Multiplex and/or simplex PCR assays have been developed for 15 serotypes based on serotype-specific genes in the cps gene cluster. In this study, we developed a set of multiplex PCR (mPCR) assays to identify the 33 currently known S. suis serotypes. To identify serotype-specific genes for mPCR, the entire genomes of reference strains for the 33 serotypes were sequenced using whole genome high-throughput sequencing, and the cps gene clusters from these strains were identified and compared. We developed a set of 4 mPCR assays based on the polysaccharide polymerase gene wzy, one of the serotype-specific genes. The assays can identify all serotypes except for two pairs of serotypes: 1 and 14, and 2 and 1/2, which have no serotype-specific genes between them. The first assay identifies 12 serotypes (serotypes 1 to 10, 1/2, and 14) that are the most frequently isolated from diseased pigs and patients; the second identifies 10 serotypes (serotypes 11 to 21 except 14); the third identifies the remaining 11 serotypes (serotypes 22 to 31, and 33); and the fourth identifies a new cps cluster of S. suis discovered in this study in 16 isolates that agglutinated with antisera for serotypes 29 and 21. The multiplex PCR assays developed in this study provide a rapid and specific method for molecular serotyping of S. suis.
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- 2013
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12. Toll-like receptor 2-independent host innate immune response against an epidemic strain of Streptococcus suis that causes a toxic shock-like syndrome in humans.
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Claude Lachance, Mariela Segura, Pehuén Pereyra Gerber, Jianguo Xu, and Marcelo Gottschalk
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Medicine ,Science - Abstract
Streptococcus suis is an emerging zoonotic agent causing meningitis and septicemia. Outbreaks in humans in China with atypical cases of streptococcal toxic shock-like syndrome have been described to be caused by a clonal epidemic S. suis strain characterized as sequence type (ST) 7 by multilocus sequence typing, different from the classical ST1 usually isolated in Europe. Previous in vitro studies showed that Toll-like receptor (TLR) 2 plays a major role in S. suis ST1 interactions with host cells. In the present study, the in vivo role of TLR2 in systemic infections caused by S. suis ST1 or ST7 strains using TLR2 deficient (TLR2(-/-)) mice was evaluated. TLR2-mediated recognition significantly contributes to the acute disease caused by the highly virulent S. suis ST1 strain, since the TLR2(-/-) mice remained unaffected when compared to wild type (WT) mice. The lack of mortality could not be associated with a lower bacterial burden; however, a significant decrease in the induction of pro-inflammatory mediators, as evaluated by microarray, real-time PCR and protein assays, was observed. On the other hand, TLR2(-/-) mice infected with the epidemic ST7 strain presented no significant differences regarding survival and expression of pro-inflammatory mediators when compared to the WT mice. Together, these results show a TLR2-independent host innate immune response to S. suis that depends on the strain.
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- 2013
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13. Immune receptors involved in Streptococcus suis recognition by dendritic cells.
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Marie-Pier Lecours, Mariela Segura, Nahuel Fittipaldi, Serge Rivest, and Marcelo Gottschalk
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Medicine ,Science - Abstract
Streptococcus suis is an important swine pathogen and an emerging zoonotic agent of septicemia and meningitis. Knowledge on host immune responses towards S. suis, and strategies used by this pathogen for subversion of these responses is scarce. The objective of this study was to identify the immune receptors involved in S. suis recognition by dendritic cells (DCs). Production of cytokines and expression of co-stimulatory molecules by DCs were shown to strongly rely on MyD88-dependent signaling pathways, suggesting that DCs recognize S. suis and become activated mostly through Toll-like receptor (TLR) signaling. Supporting this fact, TLR2(-/-) DCs were severely impaired in the release of several cytokines and the surface expression of CD86 and MHC-II. The release of IL-12p70 and CXC10, and the expression of CD40 were found to depend on signaling by both TLR2 and TLR9. The release of IL-23 and CXCL1 were partially dependent on NOD2. Finally, despite the fact that MyD88 signaling was crucial for DC activation and maturation, MyD88-dependent pathways were not implicated in S. suis internalization by DCs. This first study on receptors involved in DC activation by S. suis suggests a major involvement of MyD88 signaling pathways, mainly (but not exclusively) through TLR2. A multimodal recognition involving a combination of different receptors seems essential for DC effective response to S. suis.
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- 2012
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14. Identification of genes and genomic islands correlated with high pathogenicity in Streptococcus suis using whole genome tiling microarrays.
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Xiao Zheng, Han Zheng, Ruiting Lan, Changyun Ye, Yiting Wang, Ji Zhang, Huaiqi Jing, Chen Chen, Mariela Segura, Marcelo Gottschalk, and Jianguo Xu
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Medicine ,Science - Abstract
Streptococcus suis is an important zoonotic pathogen that can cause meningitis and sepsis in both pigs and humans. Infections in humans have been sporadic worldwide but two severe outbreaks occurred in China in recent years, while infections in pigs are a major problem in the swine industry. Some S. suis strains are more pathogenic than others with 2 sequence types (ST), ST1 and ST7, being well recognized as highly pathogenic. We analyzed 31 isolates from 23 serotypes and 25 STs by NimbleGen tiling microarray using the genome of a high pathogenicity (HP) ST1 strain, GZ1, as reference and a new algorithm to detect gene content difference. The number of genes absent in a strain ranged from 49 to 225 with a total of 632 genes absent in at least one strain, while 1346 genes were found to be invariably present in all strains as the core genome of S. suis, accounting for 68% of the GZ1 genome. The majority of genes are located in chromosomal blocks with two or more contiguous genes. Sixty two blocks are absent in two or more strains and defined as regions of difference (RDs), among which 26 are putative genomic islands (GIs). Clustering and statistical analyses revealed that 8 RDs including 6 putative GIs and 21 genes within these RDs are significantly associated with HP. Three RDs encode known virulence related factors including the extracellular factor, the capsular polysaccharide and a SrtF pilus. The strains were divided into 5 groups based on population genetic analysis of multilocus sequence typing data and the distribution of the RDs among the groups revealed gain and loss of RDs in different groups. Our study elucidated the gene content diversity of S. suis and identified genes that potentially promote HP.
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- 2011
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15. Mutations in the gene encoding the ancillary pilin subunit of the Streptococcus suis srtF cluster result in pili formed by the major subunit only.
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Nahuel Fittipaldi, Daisuke Takamatsu, María de la Cruz Domínguez-Punaro, Marie-Pier Lecours, Diane Montpetit, Makoto Osaki, Tsutomu Sekizaki, and Marcelo Gottschalk
- Subjects
Medicine ,Science - Abstract
Pili have been shown to contribute to the virulence of different Gram-positive pathogenic species. Among other critical steps of bacterial pathogenesis, these structures participate in adherence to host cells, colonization and systemic virulence. Recently, the presence of at least four discrete gene clusters encoding putative pili has been revealed in the major swine pathogen and emerging zoonotic agent Streptococcus suis. However, pili production by this species has not yet been demonstrated. In this study, we investigated the functionality of one of these pili clusters, known as the srtF pilus cluster, by the construction of mutant strains for each of the four genes of the cluster as well as by the generation of antibodies against the putative pilin subunits. Results revealed that the S. suis serotype 2 strain P1/7, as well as several other highly virulent invasive S. suis serotype 2 isolates express pili from this cluster. However, in most cases tested, and as a result of nonsense mutations at the 5' end of the gene encoding the minor pilin subunit (a putative adhesin), pili were formed by the major pilin subunit only. We then evaluated the role these pili play in S. suis virulence. Abolishment of the expression of srtF cluster-encoded pili did not result in impaired interactions of S. suis with porcine brain microvascular endothelial cells. Furthermore, non-piliated mutants were as virulent as the wild type strain when evaluated in a murine model of S. suis sepsis. Our results show that srtF cluster-encoded, S. suis pili are atypical compared to other Gram-positive pili. In addition, since the highly virulent strains under investigation are unlikely to produce other pili, our results suggest that pili might be dispensable for critical steps of the S. suis pathogenesis of infection.
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- 2010
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16. Rapid evolution of virulence and drug resistance in the emerging zoonotic pathogen Streptococcus suis.
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Matthew T G Holden, Heidi Hauser, Mandy Sanders, Thi Hoa Ngo, Inna Cherevach, Ann Cronin, Ian Goodhead, Karen Mungall, Michael A Quail, Claire Price, Ester Rabbinowitsch, Sarah Sharp, Nicholas J Croucher, Tran Bich Chieu, Nguyen Thi Hoang Mai, To Song Diep, Nguyen Tran Chinh, Michael Kehoe, James A Leigh, Philip N Ward, Christopher G Dowson, Adrian M Whatmore, Neil Chanter, Pernille Iversen, Marcelo Gottschalk, Josh D Slater, Hilde E Smith, Brian G Spratt, Jianguo Xu, Changyun Ye, Stephen Bentley, Barclay G Barrell, Constance Schultsz, Duncan J Maskell, and Julian Parkhill
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Medicine ,Science - Abstract
BACKGROUND:Streptococcus suis is a zoonotic pathogen that infects pigs and can occasionally cause serious infections in humans. S. suis infections occur sporadically in human Europe and North America, but a recent major outbreak has been described in China with high levels of mortality. The mechanisms of S. suis pathogenesis in humans and pigs are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS:The sequencing of whole genomes of S. suis isolates provides opportunities to investigate the genetic basis of infection. Here we describe whole genome sequences of three S. suis strains from the same lineage: one from European pigs, and two from human cases from China and Vietnam. Comparative genomic analysis was used to investigate the variability of these strains. S. suis is phylogenetically distinct from other Streptococcus species for which genome sequences are currently available. Accordingly, approximately 40% of the approximately 2 Mb genome is unique in comparison to other Streptococcus species. Finer genomic comparisons within the species showed a high level of sequence conservation; virtually all of the genome is common to the S. suis strains. The only exceptions are three approximately 90 kb regions, present in the two isolates from humans, composed of integrative conjugative elements and transposons. Carried in these regions are coding sequences associated with drug resistance. In addition, small-scale sequence variation has generated pseudogenes in putative virulence and colonization factors. CONCLUSIONS/SIGNIFICANCE:The genomic inventories of genetically related S. suis strains, isolated from distinct hosts and diseases, exhibit high levels of conservation. However, the genomes provide evidence that horizontal gene transfer has contributed to the evolution of drug resistance.
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- 2009
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17. Interactions of Streptococcus suis serotype 9 with host cells and role of the capsular polysaccharide: Comparison with serotypes 2 and 14
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Mariela Segura, Jean-Philippe Auger, Servane Payen, Marcelo Gottschalk, Audrey Dumesnil, and David Roy
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Serotype ,Streptococcus suis ,Physiology ,Immune Receptors ,Biochemistry ,Bacterial Adhesion ,Pathogenesis ,chemistry.chemical_compound ,Mice ,Zoonoses ,Medicine and Health Sciences ,Pathogen ,Toll-like Receptors ,0303 health sciences ,Multidisciplinary ,Immune System Proteins ,Organic Compounds ,Monosaccharides ,Animal Models ,3. Good health ,Body Fluids ,Mutant Strains ,Chemistry ,Blood ,Infectious Diseases ,Experimental Organism Systems ,Cell Processes ,Physical Sciences ,Host-Pathogen Interactions ,Medicine ,Female ,Anatomy ,Research Article ,Signal Transduction ,Phagocytosis ,Science ,Immunology ,Carbohydrates ,Virulence ,Mouse Models ,Respiratory Mucosa ,Biology ,Research and Analysis Methods ,Serogroup ,Sudden death ,Microbiology ,03 medical and health sciences ,Model Organisms ,Virology ,Genetics ,Animals ,Bacterial Capsules ,030304 developmental biology ,030306 microbiology ,Host Cells ,Organic Chemistry ,Chemical Compounds ,Biology and Life Sciences ,Proteins ,Cell Biology ,biology.organism_classification ,Sialic acid ,chemistry ,Mutation ,Animal Studies ,Sialic Acids ,Viral Transmission and Infection - Abstract
Streptococcus suis is an important porcine bacterial pathogen and a zoonotic agent responsible for sudden death, septic shock and meningitis, of which serotype 2 is the most widespread, with serotype 14 also causing infections in humans in South-East Asia. Knowledge of its pathogenesis and virulence are almost exclusively based on these two serotypes. Though serotype 9 is responsible for the greatest number of porcine cases in Spain, the Netherlands and Germany, very little information is currently available regarding this serotype. Of the different virulence factors, the capsular polysaccharide (CPS) is required for S. suis virulence as it promotes resistance to phagocytosis and killing and masks surface components responsible for host cell activation. However, these roles have been described for serotypes 2 and 14, whose CPSs are structurally and compositionally similar, both containing sialic acid. Consequently, we evaluated herein the interactions of serotype 9 with host cells and the role of its CPS, which greatly differs from those of serotypes 2 and 14. Results demonstrated that serotype 9 adhesion to but not invasion of respiratory epithelial cells was greater than that of serotypes 2 and 14. Furthermore serotype 9 was more internalized by macrophages but equally resistant to whole blood killing. Though recognition of serotypes 2, 9 and 14 by DCs required MyD88-dependent signaling, in vitro pro-inflammatory mediator production induced by serotype 9 was much lower. In vivo, however, serotype 9 causes an exacerbated inflammatory response, which combined with persistent bacterial presence, is probably responsible for host death during the systemic infection. Though presence of the serotype 9 CPS masks surface components less efficiently than those of serotypes 2 and 14, the serotype 9 CPS remains critical for virulence as it is required for survival in blood and development of clinical disease, and this regardless of its unique composition and structure.
- Published
- 2019
18. Role of the Streptococcus suis serotype 2 capsular polysaccharide in the interactions with dendritic cells is strain-dependent but remains critical for virulence
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Marcelo Gottschalk, Dominic Dolbec, Mariela Segura, David Roy, and Jean-Philippe Auger
- Subjects
0301 basic medicine ,Serotype ,Streptococcus suis ,Physiology ,Glycobiology ,lcsh:Medicine ,medicine.disease_cause ,Pathology and Laboratory Medicine ,Biochemistry ,Mice ,Zoonoses ,Immune Physiology ,Medicine and Health Sciences ,lcsh:Science ,Pathogen ,Innate Immune System ,Multidisciplinary ,Streptococcus suis serotype 2 ,Virulence ,Polysaccharides, Bacterial ,Animal Models ,Body Fluids ,Infectious Diseases ,Blood ,Experimental Organism Systems ,Cell Processes ,Cytokines ,Female ,Anatomy ,Pathogens ,Cell activation ,Hydrophobic and Hydrophilic Interactions ,Research Article ,Virulence Factors ,030106 microbiology ,Immunology ,Mouse Models ,Biology ,Research and Analysis Methods ,Sudden death ,Microbiology ,03 medical and health sciences ,Model Organisms ,Phagocytosis ,Species Specificity ,Polysaccharides ,Streptococcal Infections ,medicine ,Escherichia coli ,Animals ,Animal Models of Disease ,Bacterial Capsules ,Innate immune system ,lcsh:R ,Biology and Life Sciences ,Dendritic Cells ,Cell Biology ,Molecular Development ,Animal Models of Infection ,030104 developmental biology ,Immune System ,Animal Studies ,lcsh:Q ,Developmental Biology - Abstract
Streptococcus suis serotype 2 is an important porcine bacterial pathogen and zoonotic agent responsible for sudden death, septic shock, and meningitis. However, serotype 2 strains are heterogeneous, composed of a multitude of sequence types (STs) whose distribution greatly varies worldwide. Of the virulence factors presently described for S. suis, the capsular polysaccharide (CPS) is a critical factor implicated in a multitude of functions, including in impairment of phagocytosis and innate immune cell activation by masking underlying bacterial components. However, these roles have been described using Eurasian ST1 and ST7 strains, which greatly differ from North American ST25 strains. Consequently, the capacity of the CPS to mask surface antigens and putative virulence factors in non-Eurasian strains remains unknown. Herein, the role of the S. suis serotype 2 CPS of a prototype intermediate virulent North American ST25 strain, in comparison with that of a virulent European ST1 strain, with regards to interactions with dendritic cells, as well as virulence during the systemic phase of infection, was evaluated. Results demonstrated that the CPS remains critical for virulence and development of clinical disease regardless of strain background, due to its requirement for survival in blood. However, its role in the interactions with dendritic cells is strain-dependent. Consequently, certain key characteristics associated with the CPS are not necessarily applicable to all S. suis serotype 2 strains. This indicates that though certain factors may be important for S. suis serotype 2 virulence, strain background could be as determining, reiterating the need in using strains from varying backgrounds in order to better characterize the S. suis pathogenesis.
- Published
- 2018
19. The bias of experimental design, including strain background, in the determination of critical Streptococcus suis serotype 2 virulence factors
- Author
-
Sarah Chuzeville, Daniel Grenier, Jean-Philippe Auger, David Roy, Marcelo Gottschalk, Jianguo Xu, and Annabelle Mathieu-Denoncourt
- Subjects
0301 basic medicine ,Serotype ,Streptococcus suis ,lcsh:Medicine ,Pathology and Laboratory Medicine ,Biochemistry ,Virulence factor ,Epithelium ,Animal Cells ,Zoonoses ,Medicine and Health Sciences ,lcsh:Science ,Pathogen ,Multidisciplinary ,Streptococcus suis serotype 2 ,biology ,Animal Models ,Proteases ,N-Acetylmuramoyl-L-alanine Amidase ,Enzymes ,Bacterial Pathogens ,Infectious Diseases ,Experimental Organism Systems ,Medical Microbiology ,Research Design ,Pathogens ,Cellular Types ,Anatomy ,Research Article ,Virulence Factors ,Dipeptidyl Peptidase 4 ,030106 microbiology ,Virulence ,Mouse Models ,Research and Analysis Methods ,Serogroup ,Sudden death ,Microbiology ,03 medical and health sciences ,Model Organisms ,Streptococcal Infections ,Animals ,Animal Models of Disease ,Adhesins, Bacterial ,Microbial Pathogens ,Microbial Viability ,lcsh:R ,Biology and Life Sciences ,Proteins ,Epithelial Cells ,Cell Biology ,biology.organism_classification ,Fibronectins ,Bacterial adhesin ,Mice, Inbred C57BL ,Animal Models of Infection ,Disease Models, Animal ,030104 developmental biology ,Biological Tissue ,Biofilms ,Enzymology ,Animal Studies ,lcsh:Q - Abstract
Streptococcus suis serotype 2 is an important porcine bacterial pathogen and emerging zoonotic agent mainly responsible for sudden death, septic shock, and meningitis. However, serotype 2 strains are genotypically and phenotypically heterogeneous. Though a multitude of virulence factors have been described for S. suis serotype 2, the lack of a clear definition regarding which ones are truly "critical" has created inconsistencies that have only recently been highlighted. Herein, the involvement of two factors previously described as being critical for S. suis serotype 2 virulence, whether the dipeptidyl peptidase IV and autolysin, were evaluated with regards to different ascribed functions using prototype strains belonging to important sequence types. Results demonstrate a lack of reproducibility with previously published data. In fact, the role of the dipeptidyl peptidase IV and autolysin as critical virulence factors could not be confirmed. Though certain in vitro functions may be ascribed to these factors, their roles are not unique for S. suis, probably due to compensation by other factors. As such, variations and discrepancies in experimental design, including in vitro assays, cell lines, and animal models, are an important source of differences between results. Moreover, the use of different sequence types in this study demonstrates that the role attributed to a virulence factor may vary according to the S. suis serotype 2 strain background. Consequently, it is necessary to establish standard experimental designs according to the experiment and purpose in order to facilitate comparison between laboratories. Alongside, studies should include strains of diverse origins in order to prevent erroneous and biased conclusions that could affect future studies.
- Published
- 2017
20. Transcriptional Analysis of PRRSV-Infected Porcine Dendritic Cell Response to Streptococcus suis Infection Reveals Up-Regulation of Inflammatory-Related Genes Expression
- Author
-
Claude Lachance, Mariela Segura, Marcelo Gottschalk, Yingchao Wang, Gael Auray, Carl A. Gagnon, and Université de Montréal. Faculté de médecine vétérinaire
- Subjects
0301 basic medicine ,Streptococcus suis ,Swine ,Microarrays ,viruses ,animal diseases ,lcsh:Medicine ,Gene Expression ,Pathology and Laboratory Medicine ,Monocytes ,White Blood Cells ,Animal Cells ,Zoonoses ,Medicine and Health Sciences ,lcsh:Science ,Immune Response ,Cells, Cultured ,Swine Diseases ,Immunity, Cellular ,Multidisciplinary ,biology ,Coinfection ,virus diseases ,respiratory system ,3. Good health ,Up-Regulation ,Bioassays and Physiological Analysis ,Infectious Diseases ,Intracellular Pathogens ,Cell Processes ,Host-Pathogen Interactions ,Disease Susceptibility ,medicine.symptom ,Inflammation Mediators ,Cellular Types ,Pathogens ,Research Article ,Immune Cells ,030106 microbiology ,Immunology ,Porcine Reproductive and Respiratory Syndrome ,Inflammation ,Research and Analysis Methods ,Microbiology ,03 medical and health sciences ,Immune system ,Signs and Symptoms ,Phagocytosis ,Immunity ,Diagnostic Medicine ,Streptococcal Infections ,Virology ,medicine ,Genetics ,Animals ,Porcine respiratory and reproductive syndrome virus ,Antigen-presenting cell ,Blood Cells ,Intracellular parasite ,lcsh:R ,Biology and Life Sciences ,Dendritic cell ,Dendritic Cells ,Cell Biology ,Porcine reproductive and respiratory syndrome virus ,biology.organism_classification ,030104 developmental biology ,Co-Infections ,lcsh:Q - Abstract
The porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important swine pathogens and often serves as an entry door for other viral or bacterial pathogens, of which Streptococcus suis is one of the most common. Pre-infection with PRRSV leads to exacerbated disease caused by S. suis infection. Very few studies have assessed the immunological mechanisms underlying this higher susceptibility. Since antigen presenting cells play a major role in the initiation of the immune response, the in vitro transcriptional response of bone marrow-derived dendritic cells (BMDCs) and monocytes in the context of PRRSV and S. suis co-infection was investigated. BMDCs were found to be more permissive than monocytes to PRRSV infection; S. suis phagocytosis by PRRSV-infected BMDCs was found to be impaired, whereas no effect was found on bacterial intracellular survival. Transcription profile analysis, with a major focus on inflammatory genes, following S. suis infection, with and without pre-infection with PRRSV, was then performed. While PRRSV pre-infection had little effect on monocytes response to S. suis infection, a significant expression of several pro-inflammatory molecules was observed in BMDCs pre-infected with PRRSV after a subsequent infection with S. suis. While an additive effect could be observed for CCL4, CCL14, CCL20, and IL-15, a distinct synergistic up-regulatory effect was observed for IL-6, CCL5 and TNF-α after co-infection. This increased pro-inflammatory response by DCs could participate in the exacerbation of the disease observed during PRRSV and S. suis co-infection.
- Published
- 2016
21. Comparative genomic hybridization identifies virulence differences in Streptococcus suis
- Author
-
Zhijie Liu, Xiao Zheng, Han Zheng, Zhigang Cui, Shaobo Ji, Marcelo Gottschalk, Jianguo Xu, Xuemei Bai, and Ruiting Lan
- Subjects
Streptococcus suis ,Swine ,Microarrays ,lcsh:Medicine ,Bacteremia ,Mice ,Zoonoses ,Genotype ,Clade ,lcsh:Science ,Chemokine CCL2 ,Phylogeny ,Swine Diseases ,Comparative Genomic Hybridization ,Multidisciplinary ,Virulence ,Streptococci ,Genomics ,Bacterial Pathogens ,Phylogenetics ,Infectious Diseases ,Cytokines ,Medicine ,Female ,DNA microarray ,Signal Transduction ,Research Article ,Immunology ,Biology ,Microbiology ,In vivo ,Streptococcal Infections ,Virology ,Genetics ,Animals ,Humans ,Evolutionary Systematics ,Evolutionary Biology ,Tumor Necrosis Factor-alpha ,lcsh:R ,Computational Biology ,Comparative Genomics ,biology.organism_classification ,Bacterial Load ,Toll-Like Receptor 2 ,Toll-Like Receptor 6 ,Immune System ,Virulence Factors and Mechanisms ,lcsh:Q ,Comparative genomic hybridization - Abstract
Streptococcus suis is an important zoonotic pathogen. However, identification of virulent S. suis strains is complicated because of the high diversity of the species. Here we evaluated the genetic difference among S. suis strains using comparative genomic hybridization (CGH) and virulence variation in vivo and in vitro. We showed that different clades differed in their ability to activate TLR2/6 in vitro and their capacity to induce cytokine production in vivo as well as their resistance to phagocytosis and survival in vivo. Our data showed the S. suis strains tested can be classified into three groups having differing levels of virulence: epidemic and highly virulent strains were clustered into clade Ia (epidemic and highly virulent group, E/HV group), virulent strains were clustered into clade Ib (virulent group, V group), and intermediately or weakly virulent strains were clustered into other clades (intermediately or weakly virulent group, I/WV group). Our study provided further insight into the genomic and virulence variation of S. suis.
- Published
- 2014
22. Development of Multiplex PCR Assays for the Identification of the 33 Serotypes of Streptococcus suis
- Author
-
Marcelo Gottschalk, Shaobo Ji, Zhijie Liu, Haican Liu, Jianguo Xu, Han Zheng, Ruiting Lan, and Xuemei Bai
- Subjects
Bacterial capsule ,Serotype ,Streptococcus suis ,Swine ,lcsh:Medicine ,medicine.disease_cause ,Microbiology ,law.invention ,law ,Streptococcal Infections ,Gene cluster ,Multiplex polymerase chain reaction ,medicine ,Animals ,Humans ,Multiplex ,Serotyping ,lcsh:Science ,Polymerase chain reaction ,Bacterial Capsules ,Phylogeny ,Multidisciplinary ,biology ,lcsh:R ,Polysaccharides, Bacterial ,High-Throughput Nucleotide Sequencing ,biology.organism_classification ,Virology ,Streptococcus pyogenes ,lcsh:Q ,Multiplex Polymerase Chain Reaction ,Genome, Bacterial ,Research Article - Abstract
Streptococcus suis is an important zoonotic agent causing severe diseases in pigs and humans. To date, 33 serotypes of S . suis have been identified based on antigenic differences in the capsular polysaccharide. The capsular polysaccharide synthesis (cps) locus encodes proteins/enzymes that are responsible for capsular production and variation in the capsule structures are the basis of S . suis serotyping. Multiplex and/or simplex PCR assays have been developed for 15 serotypes based on serotype-specific genes in the cps gene cluster. In this study, we developed a set of multiplex PCR (mPCR) assays to identify the 33 currently known S . suis serotypes. To identify serotype-specific genes for mPCR, the entire genomes of reference strains for the 33 serotypes were sequenced using whole genome high-throughput sequencing, and the cps gene clusters from these strains were identified and compared. We developed a set of 4 mPCR assays based on the polysaccharide polymerase gene wzy, one of the serotype-specific genes. The assays can identify all serotypes except for two pairs of serotypes: 1 and 14, and 2 and 1/2, which have no serotype-specific genes between them. The first assay identifies 12 serotypes (serotypes 1 to 10, 1/2, and 14) that are the most frequently isolated from diseased pigs and patients; the second identifies 10 serotypes (serotypes 11 to 21 except 14); the third identifies the remaining 11 serotypes (serotypes 22 to 31, and 33); and the fourth identifies a new cps cluster of S . suis discovered in this study in 16 isolates that agglutinated with antisera for serotypes 29 and 21. The multiplex PCR assays developed in this study provide a rapid and specific method for molecular serotyping of S . suis .
- Published
- 2013
23. Population Structure and Antimicrobial Resistance Profiles of Streptococcus suis Serotype 2 Sequence Type 25 Strains
- Author
-
Marcelo Gottschalk, Nahuel Fittipaldi, Jessica Wasserscheid, Ken Dewar, Daisuke Takamatsu, Taryn B. T. Athey, and Sarah Teatero
- Subjects
0301 basic medicine ,Serotype ,Streptococcus suis ,Swine ,lcsh:Medicine ,Pathology and Laboratory Medicine ,Biochemistry ,Database and Informatics Methods ,Zoonoses ,Gene Order ,Medicine and Health Sciences ,lcsh:Science ,Phylogeny ,Recombination, Genetic ,Mammals ,Genetics ,Mammalian Genomics ,Multidisciplinary ,Streptococcus suis serotype 2 ,Phylogenetic tree ,High-Throughput Nucleotide Sequencing ,Agriculture ,Genomics ,Genomic Databases ,Anti-Bacterial Agents ,Nucleic acids ,Infectious Diseases ,Vertebrates ,Horizontal gene transfer ,Cellular Structures and Organelles ,Pathogens ,Research Article ,Pathogen Motility ,Livestock ,Virulence Factors ,DNA recombination ,030106 microbiology ,Locus (genetics) ,Microbial Sensitivity Tests ,Biology ,Serogroup ,Research and Analysis Methods ,Polymorphism, Single Nucleotide ,Microbiology ,03 medical and health sciences ,Microbial Control ,Drug Resistance, Bacterial ,Animals ,Pharmacology ,lcsh:R ,Organisms ,Biology and Life Sciences ,Computational Biology ,Cell Biology ,DNA ,Comparative Genomics ,Genome Analysis ,biology.organism_classification ,Pathogenicity island ,Biological Databases ,Pili and Fimbriae ,030104 developmental biology ,Animal Genomics ,DNA Transposable Elements ,Multilocus sequence typing ,lcsh:Q ,Antimicrobial Resistance ,Genome, Bacterial - Abstract
Strains of serotype 2 Streptococcus suis are responsible for swine and human infections. Different serotype 2 genetic backgrounds have been defined using multilocus sequence typing (MLST). However, little is known about the genetic diversity within each MLST sequence type (ST). Here, we used whole-genome sequencing to test the hypothesis that S. suis serotype 2 strains of the ST25 lineage are genetically heterogeneous. We evaluated 51 serotype 2 ST25 S. suis strains isolated from diseased pigs and humans in Canada, the United States of America, and Thailand. Whole-genome sequencing revealed numerous large-scale rearrangements in the ST25 genome, compared to the genomes of ST1 and ST28 S. suis strains, which result, among other changes, in disruption of a pilus island locus. We report that recombination and lateral gene transfer contribute to ST25 genetic diversity. Phylogenetic analysis identified two main and distinct Thai and North American clades grouping most strains investigated. These clades also possessed distinct patterns of antimicrobial resistance genes, which correlated with acquisition of different integrative and conjugative elements (ICEs). Some of these ICEs were found to be integrated at a recombination hot spot, previously identified as the site of integration of the 89K pathogenicity island in serotype 2 ST7 S. suis strains. Our results highlight the limitations of MLST for phylogenetic analysis of S. suis, and the importance of lateral gene transfer and recombination as drivers of diversity in this swine pathogen and zoonotic agent.
- Published
- 2016
24. Identification of Genes and Genomic Islands Correlated with High Pathogenicity in Streptococcus suis Using Whole Genome Tilling Microarrays
- Author
-
Mariela Segura, Xiao Zheng, Yiting Wang, Huaiqi Jing, Ji Zhang, Jianguo Xu, Han Zheng, Chen Chen, Changyun Ye, Ruiting Lan, and Marcelo Gottschalk
- Subjects
Bacterial Diseases ,Streptococcus suis ,lcsh:Medicine ,Pathogenesis ,Genome ,Genetic analysis ,Zoonoses ,Cluster Analysis ,lcsh:Science ,Genome Evolution ,Phylogeny ,Oligonucleotide Array Sequence Analysis ,Genetics ,0303 health sciences ,education.field_of_study ,Multidisciplinary ,biology ,Streptococci ,Genomics ,Reference Standards ,3. Good health ,Functional Genomics ,Bacterial Pathogens ,Infectious Diseases ,Medicine ,DNA Probes ,Research Article ,Genomic Islands ,Population ,Single-nucleotide polymorphism ,Genome Complexity ,Microbiology ,Polymorphism, Single Nucleotide ,Evolution, Molecular ,03 medical and health sciences ,Streptococcal Infections ,education ,Gene ,Biology ,030304 developmental biology ,Comparative genomics ,030306 microbiology ,lcsh:R ,Comparative Genomics ,biology.organism_classification ,Emerging Infectious Diseases ,Genes, Bacterial ,Multilocus sequence typing ,lcsh:Q ,Multilocus Sequence Typing - Abstract
Streptococcus suis is an important zoonotic pathogen that can cause meningitis and sepsis in both pigs and humans. Infections in humans have been sporadic worldwide but two severe outbreaks occurred in China in recent years, while infections in pigs are a major problem in the swine industry. Some S. suis strains are more pathogenic than others with 2 sequence types (ST), ST1 and ST7, being well recognized as highly pathogenic. We analyzed 31 isolates from 23 serotypes and 25 STs by NimbleGen tiling microarray using the genome of a high pathogenicity (HP) ST1 strain, GZ1, as reference and a new algorithm to detect gene content difference. The number of genes absent in a strain ranged from 49 to 225 with a total of 632 genes absent in at least one strain, while 1346 genes were found to be invariably present in all strains as the core genome of S. suis, accounting for 68% of the GZ1 genome. The majority of genes are located in chromosomal blocks with two or more contiguous genes. Sixty two blocks are absent in two or more strains and defined as regions of difference (RDs), among which 26 are putative genomic islands (GIs). Clustering and statistical analyses revealed that 8 RDs including 6 putative GIs and 21 genes within these RDs are significantly associated with HP. Three RDs encode known virulence related factors including the extracellular factor, the capsular polysaccharide and a SrtF pilus. The strains were divided into 5 groups based on population genetic analysis of multilocus sequence typing data and the distribution of the RDs among the groups revealed gain and loss of RDs in different groups. Our study elucidated the gene content diversity of S. suis and identified genes that potentially promote HP.
- Published
- 2011
25. Complex Population Structure and Virulence Differences among Serotype 2 Streptococcus suis Strains Belonging to Sequence Type 28
- Author
-
Daisuke Takamatsu, Sarah Teatero, Marcelo Gottschalk, Taryn B. T. Athey, Audrey Dumesnil, Ken Dewar, Nahuel Fittipaldi, Jessica Wasserscheid, and Jean-Philippe Auger
- Subjects
DNA, Bacterial ,Serotype ,Canada ,Streptococcus suis ,Swine ,Molecular Sequence Data ,Population Dynamics ,lcsh:Medicine ,Virulence ,Microbiology ,Mice ,Japan ,Species Specificity ,Streptococcal Infections ,Animals ,Humans ,lcsh:Science ,Clade ,Pathogen ,Phylogeny ,Swine Diseases ,Multidisciplinary ,Phylogenetic tree ,biology ,Strain (biology) ,lcsh:R ,biology.organism_classification ,United States ,3. Good health ,Mice, Inbred C57BL ,Multilocus sequence typing ,lcsh:Q ,Research Article ,Multilocus Sequence Typing - Abstract
Streptococcus suis is a major swine pathogen and a zoonotic agent. Serotype 2 strains are the most frequently associated with disease. However, not all serotype 2 lineages are considered virulent. Indeed, sequence type (ST) 28 serotype 2 S. suis strains have been described as a homogeneous group of low virulence. However, ST28 strains are often isolated from diseased swine in some countries, and at least four human ST28 cases have been reported. Here, we used whole-genome sequencing and animal infection models to test the hypothesis that the ST28 lineage comprises strains of different genetic backgrounds and different virulence. We used 50 S. suis ST28 strains isolated in Canada, the United States and Japan from diseased pigs, and one ST28 strain from a human case isolated in Thailand. We report a complex population structure among the 51 ST28 strains. Diversity resulted from variable gene content, recombination events and numerous genome-wide polymorphisms not attributable to recombination. Phylogenetic analysis using core genome single-nucleotide polymorphisms revealed four discrete clades with strong geographic structure, and a fifth clade formed by US, Thai and Japanese strains. When tested in experimental animal models, strains from this latter clade were significantly more virulent than a Canadian ST28 reference strain, and a closely related Canadian strain. Our results highlight the limitations of MLST for both phylogenetic analysis and virulence prediction and raise concerns about the possible emergence of ST28 strains in human clinical cases.
- Published
- 2015
26. Suicin 3908, a New Lantibiotic Produced by a Strain of Streptococcus suis Serotype 2 Isolated from a Healthy Carrier Pig
- Author
-
Geneviève LeBel, Katy Vaillancourt, Marcelo Gottschalk, Michel Frenette, and Daniel Grenier
- Subjects
Serotype ,Streptococcus thermophilus ,Streptococcus suis ,Swine ,medicine.drug_class ,Antibiotics ,lcsh:Medicine ,Microbiology ,Open Reading Frames ,Bacteriocins ,Bacteriocin ,medicine ,Animals ,lcsh:Science ,Multidisciplinary ,Streptococcus suis serotype 2 ,biology ,lcsh:R ,Amoxicillin ,biology.organism_classification ,Streptococcus bovis ,Virology ,Genes, Bacterial ,Multigene Family ,lcsh:Q ,Research Article ,medicine.drug - Abstract
While Streptococcus suis serotype 2 is known to cause severe infections in pigs, it can also be isolated from the tonsils of healthy animals that do not develop infections. We hypothesized that S. suis strains in healthy carrier pigs may have the ability to produce bacteriocins, which may contribute to preventing infections by pathogenic S. suis strains. Two of ten S. suis serotype 2 strains isolated from healthy carrier pigs exhibited antibacterial activity against pathogenic S. suis isolates. The bacteriocin produced by S. suis 3908 was purified to homogeneity using a three-step procedure: ammonium sulfate precipitation, cationic exchange HPLC, and reversed-phase HPLC. The bacteriocin, called suicin 3908, had a low molecular mass; was resistant to heat, pH, and protease treatments; and possessed membrane permeabilization activity. Additive effects were obtained when suicin 3908 was used in combination with penicillin G or amoxicillin. The amino acid sequence of suicin 3908 suggested that it is lantibiotic-related and made it possible to identify a bacteriocin locus in the genome of S. suis D12. The putative gene cluster involved in suicin production by S. suis 3908 was amplified by PCR, and the sequence analysis revealed the presence of nine open reading frames (ORFs), including the structural gene and those required for the modification of amino acids, export, regulation, and immunity. Suicin 3908, which is encoded by the suiA gene, exhibited approximately 50% identity with bovicin HJ50 (Streptococcus bovis), thermophilin 1277 (Streptococcus thermophilus), and macedovicin (Streptococcus macedonicus). Given that S. suis 3908 cannot cause infections in animal models, that it is susceptible to conventional antibiotics, and that it produces a bacteriocin with antibacterial activity against all pathogenic S. suis strains tested, it could potentially be used to prevent infections and to reduce antibiotic use by the swine industry.
- Published
- 2015
27. Mutations in the Gene Encoding the Ancillary Pilin Subunit of the Streptococcus suis srtF Cluster Result in Pili Formed by the Major Subunit Only
- Author
-
Daisuke Takamatsu, Nahuel Fittipaldi, Marie-Pier Lecours, Tsutomu Sekizaki, Marcelo Gottschalk, Diane Montpetit, Makoto Osaki, and María de la Cruz Domínguez-Punaro
- Subjects
Streptococcus suis ,Blotting, Western ,Mutant ,lcsh:Medicine ,Virulence ,Mice, Transgenic ,Pilus ,Microbiology ,Fimbriae Proteins ,Infectious Diseases/Bacterial Infections ,Mice ,03 medical and health sciences ,Bacterial Proteins ,Sepsis ,Cell Adhesion ,Animals ,lcsh:Science ,Pathogen ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,biology ,030306 microbiology ,lcsh:R ,Microbiology/Medical Microbiology ,biology.organism_classification ,3. Good health ,Bacterial adhesin ,Microscopy, Electron ,Genes, Bacterial ,Multigene Family ,Pilin ,Mutation ,biology.protein ,lcsh:Q ,Microbiology/Cellular Microbiology and Pathogenesis ,Research Article - Abstract
Pili have been shown to contribute to the virulence of different Gram-positive pathogenic species. Among other critical steps of bacterial pathogenesis, these structures participate in adherence to host cells, colonization and systemic virulence. Recently, the presence of at least four discrete gene clusters encoding putative pili has been revealed in the major swine pathogen and emerging zoonotic agent Streptococcus suis. However, pili production by this species has not yet been demonstrated. In this study, we investigated the functionality of one of these pili clusters, known as the srtF pilus cluster, by the construction of mutant strains for each of the four genes of the cluster as well as by the generation of antibodies against the putative pilin subunits. Results revealed that the S. suis serotype 2 strain P1/7, as well as several other highly virulent invasive S. suis serotype 2 isolates express pili from this cluster. However, in most cases tested, and as a result of nonsense mutations at the 5' end of the gene encoding the minor pilin subunit (a putative adhesin), pili were formed by the major pilin subunit only. We then evaluated the role these pili play in S. suis virulence. Abolishment of the expression of srtF cluster-encoded pili did not result in impaired interactions of S. suis with porcine brain microvascular endothelial cells. Furthermore, non-piliated mutants were as virulent as the wild type strain when evaluated in a murine model of S. suis sepsis. Our results show that srtF cluster-encoded, S. suis pili are atypical compared to other Gram-positive pili. In addition, since the highly virulent strains under investigation are unlikely to produce other pili, our results suggest that pili might be dispensable for critical steps of the S. suis pathogenesis of infection.
- Published
- 2010
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