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A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: closed (31 December 2016) | Viewed by 75460

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Dr. Mariela Segura

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Faculty of Veterinary Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada
Interests: study the cellular and molecular basis of innate and adaptive immunity to capsular polysaccharides of pathogenic bacteria and the role of dendritic cells (DCs) in orchestrating these responses; special interest on Streptococcus suis research and vaccine development
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Dear Colleagues,

Streptococcus suis is a swine pathogen responsible for important economic losses in the swine industry worldwide. This pathogen has gained more attention since recent recognition of its high prevalence in human meningitis cases in South East and East Asia, and reports of outbreaks which resulted in high mortality rates. Despite the increased incidence and severity of the S. suis infection and the changing epidemiology of this bacterial disease, an effective vaccine to control disease in swine is not really available. Studies in the past few years have identified new potential virulence factors through proteomic and genomic approaches, yet the pathogenesis of the disease is still poorly understood. Identification of new serotypes or reclassification of old ones is also a matter of controversy. For this Special Issue of Pathogens, we invite you to submit research articles, review articles, short notes as well as communications related to S. suis molecular and epidemiological aspects, bacterial–host interactions, the immune response and vaccine development. We look forward to your contribution.

Dr. Mariela Segura
Guest Editor

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Keywords

Streptococcus suis
serotype
virulence factor
innate immunity
adaptive immunity
vaccine
animal models

Published Papers (12 papers)

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Research

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3219 KiB

Open AccessArticle

Evaluation of the Immunomodulatory Properties of Streptococcus suis and Group B Streptococcus Capsular Polysaccharides on the Humoral Response

by Cynthia Calzas, Morgan Taillardet, Insaf Salem Fourati, David Roy, Marcelo Gottschalk, Hugo Soudeyns, Thierry Defrance and Mariela Segura

Pathogens 2017, 6(2), 16; https://doi.org/10.3390/pathogens6020016 - 20 Apr 2017

Cited by 11 | Viewed by 4448

Abstract

Streptococcus suis and group B Streptococcus (GBS) are encapsulated streptococci causing septicemia and meningitis. Antibodies (Abs) against capsular polysaccharides (CPSs) have a crucial protective role, but the structure/composition of the CPS, including the presence of sialic acid, may interfere with the generation of anti-CPS Ab responses. We investigated the features of the CPS-specific Ab response directed against S. suis serotypes 2 and 14 and GBS serotypes III and V after infection or immunization with purified native or desialylated CPSs in mice. Whereas S. suis-infected mice developed a very low/undetectable CPS-specific IgM response, significant anti-CPS IgM titers were measured in GBS-infected animals (especially for type III GBS). No isotype switching was detected in S. suis- or GBS-infected mice. While the expression of sialic acid was essential for the immunogenicity of purified GBS type III CPS, this sugar was not responsible for the inability of purified S. suis types 2, 14 and GBS type V CPSs to induce a specific Ab response. Thus, other biochemical criteria unrelated to the presence of sialic acid may be responsible for the inaptitude of the host immune system to mount an effective response against certain S. suis and GBS CPS types. Full article

(This article belongs to the Special Issue Streptococcus suis)

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1771 KiB

Open AccessFeature PaperArticle

Porcine Dendritic Cells as an In Vitro Model to Assess the Immunological Behaviour of Streptococcus suis Subunit Vaccine Formulations and the Polarizing Effect of Adjuvants

by Léa Martelet, Sonia Lacouture, Guillaume Goyette-Desjardins, Guy Beauchamp, Charles Surprenant, Marcelo Gottschalk and Mariela Segura

Pathogens 2017, 6(1), 13; https://doi.org/10.3390/pathogens6010013 - 22 Mar 2017

Cited by 14 | Viewed by 4598

Abstract

An in vitro porcine bone marrow-derived dendritic cell (DC) culture was developed as a model for evaluating immune polarization induced by adjuvants when administered with immunogens that may become vaccine candidates if appropriately formulated. The swine pathogen Streptococcus suis was chosen as a prototype to evaluate proposed S. suis vaccine candidates in combination with the adjuvants Poly I:C, Quil A ®, Alhydrogel ®, TiterMax Gold ® and Stimune ®. The toll-like receptor ligand Poly I:C and the saponin Quil A ® polarized swine DC cytokines towards a type 1 phenotype, with preferential production of IL-12 and TNF-α. The water-in-oil adjuvants TiterMax Gold ® and Stimune ® favoured a type 2 profile as suggested by a marked IL-6 release. In contrast, Alhydrogel ® induced a type 1/type 2 mixed cytokine profile. The antigen type differently modified the magnitude of the adjuvant effect, but overall polarization was preserved. This is the first comparative report on swine DC immune activation by different adjuvants. Although further swine immunization studies would be required to better characterize the induced responses, the herein proposed in vitro model is a promising approach that helps assessing behaviour of the vaccine formulation rapidly at the pre-screening stage and will certainly reduce numbers of animals used while advancing vaccinology science. Full article

(This article belongs to the Special Issue Streptococcus suis)

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Open AccessCommunication

Transcriptomic Analysis Reveals Selective Metabolic Adaptation of Streptococcus suis to Porcine Blood and Cerebrospinal Fluid

by Anna Koczula, Michael Jarek, Christian Visscher, Peter Valentin-Weigand, Ralph Goethe and Jörg Willenborg

Pathogens 2017, 6(1), 7; https://doi.org/10.3390/pathogens6010007 - 15 Feb 2017

Cited by 9 | Viewed by 5788

Abstract

Streptococcus suis is a zoonotic pathogen that can cause severe pathologies such as septicemia and meningitis in its natural porcine host as well as in humans. Establishment of disease requires not only virulence of the infecting strain but also an appropriate metabolic activity of the pathogen in its host environment. However, it is yet largely unknown how the streptococcal metabolism adapts to the different host niches encountered during infection. Our previous isotopologue profiling studies on S. suis grown in porcine blood and cerebrospinal fluid (CSF) revealed conserved activities of central carbon metabolism in both body fluids. On the other hand, they suggested differences in the de novo amino acid biosynthesis. This prompted us to further dissect S. suis adaptation to porcine blood and CSF by RNA deep sequencing (RNA-seq). In blood, the majority of differentially expressed genes were associated with transport of alternative carbohydrate sources and the carbohydrate metabolism (pentose phosphate pathway, glycogen metabolism). In CSF, predominantly genes involved in the biosynthesis of branched-chain and aromatic amino acids were differentially expressed. Especially, isoleucine biosynthesis seems to be of major importance for S. suis in CSF because several related biosynthetic genes were more highly expressed. In conclusion, our data revealed niche-specific metabolic gene activity which emphasizes a selective adaptation of S. suis to host environments. Full article

(This article belongs to the Special Issue Streptococcus suis)

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Open AccessCommunication

Distribution of Type I Restriction–Modification Systems in Streptococcus suis: An Outlook

by Niels Willemse and Constance Schultsz

Pathogens 2016, 5(4), 62; https://doi.org/10.3390/pathogens5040062 - 18 Nov 2016

Cited by 22 | Viewed by 4985

Abstract

Streptococcus suis is a porcine commensal and pathogen with zoonotic potential. We recently identified a novel Type I restriction–modification (R–M) system in a zoonotic S. suis clone which has emerged in the Netherlands. Here, we describe the DNA inversions in the specificity subunit of this system in S. suis serotype 2, clonal complex 20 and explain the absence of domain movement by the absence of repeats. In addition, we identified a core Type I R–M system present in 95% of the isolates and found an association of the distribution of Type I R–M systems in the S. suis genome with population structure. We speculate on the potential role of Type I R–M systems in S. suis given the recently described associations of Type I R–M systems with virulence and propose future research directions. Full article

(This article belongs to the Special Issue Streptococcus suis)

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Open AccessArticle

Clearance of Streptococcus suis in Stomach Contents of Differently Fed Growing Pigs

by Franziska Warneboldt, Saara J. Sander, Andreas Beineke, Peter Valentin-Weigand, Josef Kamphues and Christoph Georg Baums

Pathogens 2016, 5(3), 56; https://doi.org/10.3390/pathogens5030056 - 06 Aug 2016

Cited by 9 | Viewed by 4708

Abstract

Streptococcus (S.) suis translocates across the intestinal barrier of piglets after intraintestinal application. Based on these findings, an oro-gastrointestinal infection route has been proposed. Thus, the objective of this study was to investigate the survival of S. suis in the porcine stomach. Whereas surviving bacteria of S. suis serotypes 2 and 9 were not detectable after 60 min of incubation in stomach contents with a comparatively high gastric pH of 5 due to feeding of fine pellets, the number of Salmonella Derby bacteria increased under these conditions. Further experiments confirmed the clearance of S. suis serotypes 2 and 9 within 30 min in stomach contents with a pH of 4.7 independently of the bacterial growth phase. Finally, an oral infection experiment was conducted, feeding each of 18 piglets a diet mixed with 10¹⁰ CFU of S. suis serotype 2 or 9. Thorough bacteriological screenings of various mesenteric-intestinal lymph nodes and internal organs after different times of exposure did not lead to any detection of the orally applied challenge strains. In conclusion, the porcine stomach constitutes a very efficient barrier against oro-gastrointenstinal S. suis infections. Conditions leading to the passage of S. suis through the stomach remain to be identified. Full article

(This article belongs to the Special Issue Streptococcus suis)

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Open AccessArticle

FlpS, the FNR-Like Protein of Streptococcus suis Is an Essential, Oxygen-Sensing Activator of the Arginine Deiminase System

by Jörg Willenborg, Anna Koczula, Marcus Fulde, Astrid De Greeff, Andreas Beineke, Wolfgang Eisenreich, Claudia Huber, Maren Seitz, Peter Valentin-Weigand and Ralph Goethe

Pathogens 2016, 5(3), 51; https://doi.org/10.3390/pathogens5030051 - 21 Jul 2016

Cited by 12 | Viewed by 10589

Abstract

Streptococcus (S.) suis is a zoonotic pathogen causing septicemia and meningitis in pigs and humans. During infection S. suis must metabolically adapt to extremely diverse environments of the host. CcpA and the FNR family of bacterial transcriptional regulators are important for metabolic gene regulation in various bacteria. The role of CcpA in S. suis is well defined, but the function of the FNR-like protein of S. suis, FlpS, is yet unknown. Transcriptome analyses of wild-type S. suis and a flpS mutant strain suggested that FlpS is involved in the regulation of the central carbon, arginine degradation and nucleotide metabolism. However, isotopologue profiling revealed no substantial changes in the core carbon and amino acid de novo biosynthesis. FlpS was essential for the induction of the arcABC operon of the arginine degrading pathway under aerobic and anaerobic conditions. The arcABC-inducing activity of FlpS could be associated with the level of free oxygen in the culture medium. FlpS was necessary for arcABC-dependent intracellular bacterial survival but redundant in a mice infection model. Based on these results, we propose that the core function of S. suis FlpS is the oxygen-dependent activation of the arginine deiminase system. Full article

(This article belongs to the Special Issue Streptococcus suis)

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3098 KiB

Open AccessArticle

Virulence Studies of Different Sequence Types and Geographical Origins of Streptococcus suis Serotype 2 in a Mouse Model of Infection

by Jean-Philippe Auger, Nahuel Fittipaldi, Marie-Odile Benoit-Biancamano, Mariela Segura and Marcelo Gottschalk

Pathogens 2016, 5(3), 48; https://doi.org/10.3390/pathogens5030048 - 11 Jul 2016

Cited by 43 | Viewed by 5748

Abstract

Multilocus sequence typing previously identified three predominant sequence types (STs) of Streptococcus suis serotype 2: ST1 strains predominate in Eurasia while North American (NA) strains are generally ST25 and ST28. However, ST25/ST28 and ST1 strains have also been isolated in Asia and NA, respectively. Using a well-standardized mouse model of infection, the virulence of strains belonging to different STs and different geographical origins was evaluated. Results demonstrated that although a certain tendency may be observed, S. suis serotype 2 virulence is difficult to predict based on ST and geographical origin alone; strains belonging to the same ST presented important differences of virulence and did not always correlate with origin. The only exception appears to be NA ST28 strains, which were generally less virulent in both systemic and central nervous system (CNS) infection models. Persistent and high levels of bacteremia accompanied by elevated CNS inflammation are required to cause meningitis. Although widely used, in vitro tests such as phagocytosis and killing assays require further standardization in order to be used as predictive tests for evaluating virulence of strains. The use of strains other than archetypal strains has increased our knowledge and understanding of the S. suis serotype 2 population dynamics. Full article

(This article belongs to the Special Issue Streptococcus suis)

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Open AccessFeature PaperArticle

Recruitment of Factor H to the Streptococcus suis Cell Surface is Multifactorial

by David Roy, Daniel Grenier, Mariela Segura, Annabelle Mathieu-Denoncourt and Marcelo Gottschalk

Pathogens 2016, 5(3), 47; https://doi.org/10.3390/pathogens5030047 - 07 Jul 2016

Cited by 23 | Viewed by 4642

Abstract

Streptococcus suis is an important bacterial swine pathogen and a zoonotic agent. Recently, two surface proteins of S. suis, Fhb and Fhbp, have been described for their capacity to bind factor H—a soluble complement regulatory protein that protects host cells from complement-mediated damages. Results obtained in this study showed an important role of host factor H in the adhesion of S. suis to epithelial and endothelial cells. Both Fhb and Fhbp play, to a certain extent, a role in such increased factor H-dependent adhesion. The capsular polysaccharide (CPS) of S. suis, independently of the presence of its sialic acid moiety, was also shown to be involved in the recruitment of factor H. However, a triple mutant lacking Fhb, Fhbp and CPS was still able to recruit factor H resulting in the degradation of C3b in the presence of factor I. In the presence of complement factors, the double mutant lacking Fhb and Fhbp was similarly phagocytosed by human macrophages and killed by pig blood when compared to the wild-type strain. In conclusion, this study suggests that recruitment of factor H to the S. suis cell surface is multifactorial and redundant. Full article

(This article belongs to the Special Issue Streptococcus suis)

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Open AccessArticle

Simultaneous Quantification and Differentiation of Streptococcus suis Serotypes 2 and 9 by Quantitative Real-Time PCR, Evaluated in Tonsillar and Nasal Samples of Pigs

by Niels Dekker, Ineke Daemen, Koen Verstappen, Astrid De Greeff, Hilde Smith and Birgitta Duim

Pathogens 2016, 5(3), 46; https://doi.org/10.3390/pathogens5030046 - 30 Jun 2016

Cited by 10 | Viewed by 11137

Abstract

Invasive Streptococcus suis (S. suis) infections in pigs are often associated with serotypes 2 and 9. Mucosal sites of healthy pigs can be colonized with these serotypes, often multiple serotypes per pig. To unravel the contribution of these serotypes in pathogenesis and epidemiology, simultaneous quantification of serotypes is needed. A quantitative real-time PCR (qPCR) targeting cps2J (serotypes 2 and 1/2) and cps9H (serotype 9) was evaluated with nasal and tonsillar samples from S. suis exposed pigs. qPCR specifically detected serotypes in all pig samples. The serotypes loads in pig samples estimated by qPCR showed, except for serotype 9 in tonsillar samples (correlation coefficient = 0.25), moderate to strong correlation with loads detected by culture (correlation coefficient > 0.65), and also in pigs exposed to both serotypes (correlation coefficient > 0.75). This qPCR is suitable for simultaneous differentiation and quantification of important S. suis serotypes. Full article

(This article belongs to the Special Issue Streptococcus suis)

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Open AccessCommunication

Astrocytes Enhance Streptococcus suis-Glial Cell Interaction in Primary Astrocyte-Microglial Cell Co-Cultures

by Jana Seele, Roland Nau, Chittappen K. Prajeeth, Martin Stangel, Peter Valentin-Weigand and Maren Seitz

Pathogens 2016, 5(2), 43; https://doi.org/10.3390/pathogens5020043 - 13 Jun 2016

Cited by 6 | Viewed by 5112

Abstract

Streptococcus (S.) suis infections are the most common cause of meningitis in pigs. Moreover, S. suis is a zoonotic pathogen, which can lead to meningitis in humans, mainly in adults. We assume that glial cells may play a crucial role in host-pathogen interactions during S. suis infection of the central nervous system. Glial cells are considered to possess important functions during inflammation and injury of the brain in bacterial meningitis. In the present study, we established primary astrocyte-microglial cell co-cultures to investigate interactions of S. suis with glial cells. For this purpose, microglial cells and astrocytes were isolated from new-born mouse brains and characterized by flow cytometry, followed by the establishment of astrocyte and microglial cell mono-cultures as well as astrocyte-microglial cell co-cultures. In addition, we prepared microglial cell mono-cultures co-incubated with uninfected astrocyte mono-culture supernatants and astrocyte mono-cultures co-incubated with uninfected microglial cell mono-culture supernatants. After infection of the different cell cultures with S. suis, bacteria-cell association was mainly observed with microglial cells and most prominently with a non-encapsulated mutant of S. suis. A time-dependent induction of NO release was found only in the co-cultures and after co-incubation of microglial cells with uninfected supernatants of astrocyte mono-cultures mainly after infection with the capsular mutant. Only moderate cytotoxic effects were found in co-cultured glial cells after infection with S. suis. Taken together, astrocytes and astrocyte supernatants increased interaction of microglial cells with S. suis. Astrocyte-microglial cell co-cultures are suitable to study S. suis infections and bacteria-cell association as well as NO release by microglial cells was enhanced in the presence of astrocytes. Full article

(This article belongs to the Special Issue Streptococcus suis)

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Open AccessArticle

Impact of Sub-Inhibitory Concentrations of Amoxicillin on Streptococcus suis Capsule Gene Expression and Inflammatory Potential

by Bruno Haas and Daniel Grenier

Pathogens 2016, 5(2), 37; https://doi.org/10.3390/pathogens5020037 - 19 Apr 2016

Cited by 10 | Viewed by 5448

Abstract

Streptococcus suis is an important swine pathogen and emerging zoonotic agent worldwide causing meningitis, endocarditis, arthritis and septicemia. Among the 29 serotypes identified to date, serotype 2 is mostly isolated from diseased pigs. Although several virulence mechanisms have been characterized in S. suis, the pathogenesis of S. suis infections remains only partially understood. This study focuses on the response of S. suis P1/7 to sub-inhibitory concentrations of amoxicillin. First, capsule expression was monitored by qRT-PCR when S. suis was cultivated in the presence of amoxicillin. Then, the pro-inflammatory potential of S. suis P1/7 culture supernatants or whole cells conditioned with amoxicillin was evaluated by monitoring the activation of the NF-κB pathway in monocytes and quantifying pro-inflammatory cytokines secreted by macrophages. It was found that amoxicillin decreased capsule expression in S. suis. Moreover, conditioning the bacterium with sub-inhibitory concentrations of amoxicillin caused an increased activation of the NF-κB pathway in monocytes following exposure to bacterial culture supernatants and to a lesser extent to whole bacterial cells. This was associated with an increased secretion of pro-inflammatory cytokines (CXCL8, IL-6, IL-1β) by macrophages. This study identified a new mechanism by which S. suis may increase its inflammatory potential in the presence of sub-inhibitory concentrations of amoxicillin, a cell wall-active antibiotic, thus challenging its use for preventive treatments or as growth factor. Full article

(This article belongs to the Special Issue Streptococcus suis)

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Review

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Open AccessReview

Current Taxonomical Situation of Streptococcus suis

by Masatoshi Okura, Makoto Osaki, Ryohei Nomoto, Sakura Arai, Ro Osawa, Tsutomu Sekizaki and Daisuke Takamatsu

Pathogens 2016, 5(3), 45; https://doi.org/10.3390/pathogens5030045 - 24 Jun 2016

Cited by 99 | Viewed by 7465

Abstract

Streptococcus suis, a major porcine pathogen and an important zoonotic agent, is considered to be composed of phenotypically and genetically diverse strains. However, recent studies reported several “S. suis-like strains” that were identified as S. suis by commonly used methods for the identification of this bacterium, but were regarded as distinct species from S. suis according to the standards of several taxonomic analyses. Furthermore, it has been suggested that some S. suis-like strains can be assigned to several novel species. In this review, we discuss the current taxonomical situation of S. suis with a focus on (1) the classification history of the taxon of S. suis; (2) S. suis-like strains revealed by taxonomic analyses; (3) methods for detecting and identifying this species, including a novel method that can distinguish S. suis isolates from S. suis-like strains; and (4) current topics on the reclassification of S. suis-like strains. Full article

(This article belongs to the Special Issue Streptococcus suis)

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