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Agents of the "suis-ide diseases" of swine: Actinobacillus suis, Haemophilus parasuis, and Streptococcus suis.

In recent years, Actinobacillus suis, Haemophilus parasuis, and Streptococcus suis have emerged as important pathogens of swine, particularly in high health status herds. Their association with a wide range of serious clinical conditions and has given rise to the moniker "suis-ide diseases." These organisms are early colonizers and, for that reason, are difficult to control by management procedures such as segregated early weaning. Vaccination, serodiagnostic testing, and even serotyping are complicated by the presence of multiple serotypes, cross-reactive antigens, and the absence of clear markers for virulence. In this review, we discuss our current understanding of the pathogenesis, epidemiology, and management of the causative agents of the "suis-ide diseases" of swine.

Actinobacillus Infections↗

[Streptococcus suis bacteremia].

INTRODUCTION: Streptococcus suis infection is recognised despite it rareness as a zoonotic occupational disease in humans, and is often associated with meningitis, more rarely with bacteremia. OBSERVATION: A Streptococcus suis bacteremia occurred in a hunter and was complicated by septic shock with disseminated intravascular coagulation, rhabdomyolysis and purpura fulminans. Contamination had occurred through inoculation of a cut on the thumb when the hunter was slaughtering a wild boar. The blood cultures isolated Streptococcus suis. The patient died 36 hours after admission, despite intensive care and adapted antibiotic treatment with penicillin A and macrolide. CONCLUSION: Streptococcus suis bacteremia are uncommon but serious in humans. Despite adapted treatment, evolution may be fatal, so their conditions of occurrence must be well known by hunters and practitioners.

Anti-Bacterial Agents↗

Streptococcus suis bacteraemia.

Streptococcus suis is a zoonotic pathogen which causes meningitis, arthritis and septicaemia in pigs, and rarely meningitis or septicaemia in humans. This organism has recently been isolated from pigs in New Zealand, where it appears to be widely distributed in pig herds. This case is the first report of human infection in New Zealand.

Adult↗

Streptococcus suis and group B Streptococcus differ in their interactions with murine macrophages.

Streptococcus suis type 2 and group B Streptococcus type III (GBS) are important encapsulated bacterial species causing meningitis. In the present study we compared quantitatively the uptake and intracellular survival of S. suis type 2 and GBS type III with murine macrophages in non-opsonic conditions. The role of the capsule of both pathogens was also studied using previously obtained unencapsulated isogenic mutants. Encapsulated S. suis wild-type strain was practically not phagocytosed, while the unencapsulated mutant was easily ingested by macrophages. On the other hand, the well encapsulated GBS strain and its unencapsulated mutant were both phagocytosed in large numbers. Even if S. suis unencapsulated mutant showed a higher uptake rate than the parental strain, this value was always markedly lower than the numbers of ingested GBS strains. In addition, the intracellular survival of encapsulated and unencapsulated GBS strains was significantly higher than that of S. suis strains. These results suggest that interactions between GBS type III and S. suis type 2 with murine macrophages as well as the role of the capsule as an antiphagocytic factor are different for the two bacterial pathogens.

Animals↗

[Analysis of virulence-related proteins of Streptococcus suis type 2 from swine Streptococcus isolated in China].

Virulence-related proteins, muraminidase-released protein (MRP) and extracellular factor (EF) of Streptococcus suis type 2, were extracted from Jiangsu Isolate HA9801 and were used as antigens for preparation of antibodies. Bacterium cell envelope proteins and extracellular proteins of swine Streptococcus strains including 17 Chinese isolates, 1 German strain and 1 human isolate of Streptococcus suis type 2, were analyzed by SDS-PAGE and immunoblotting using the above antibodies, 11 strains produced MRP and 10 strains possessed EF or EF. They exist four phenotypes: MRP+ EF+ (8/19), MRP+ EF (1/19), MRP+ EF- (1/19), MRP- EF- (10/19).

Animals↗

Presence of the Streptococcus suis suilysin gene and expression of MRP and EF correlates with high virulence in Streptococcus suis type 2 isolates.

Nineteen Streptococccus suis type 2 isolates that had been analyzed previously for hemolysin production, ribotype, and virulence in pigs were examined for presence of the gene coding for suilysin by PCR amplification, and southern blot and hybridization techniques. Based on southern blot and hybridization analysis, all isolates tested contained at least a portion of the suilysin gene. PCR amplification of the entire gene resulted in gene fragments from five of the seven highly virulent isolates and none of the moderately virulent or avirulent isolates. Additional PCR analysis showed that mutation or deletions at the 5' end of the suilysin gene in the less virulent isolates prevented amplification of the sly gene fragment from those isolates. The MRP+ (muramidase-released protein) EF+ (extracellular protein) phenotype was also expressed by the same five highly virulent/sly+ isolates.

Animals↗

[Streptococcus suis infection--clinical manifestations].

INTRODUCTION: Streptococcus suis is a bacterium causing a disease in pigs and rarely in humans. This zoonosis is mostly found as a sporadic disease in individuals that were in contact with the affected or infected pigs: farmers, veterinarians and workers engaged in fresh pork processing. It is assumed that the bacterium enters the body through a cut abrasion in the skin. Initially, the condition resembles a flu, followed by signs of bacteriemia and sepsis. The most frequent clinical manifestation of Streptococcus suis infection is meningitis, leading to hearing loss in over 75% of patients, and subsequent arthritis, endophtalmitis, endocarditis and pneumonia. Toxic shock syndrome with hemorhagic manifestations rarely develops. MATERIAL AND METHODS: This study included five male patients aged 22 to 63 years treated in the Intensive Care Unit of the Institute of Infectious and Tropical Diseases in Belgrade, due to Streptococcus suis infection. The aim of this study was to point to the existence of this bacteria in our environment, to describe clinical manifestations of the disease and to point out the importance of its prevention. RESULTS: All patients had epidemiological evidence of being in contact with pork meat. There were no data about diseased pigs. The estimated incubation period was 4 to 8 days. All patients had meningeal signs. Clinical symptoms included shivering, fever, vomiting, headache, malaise, vertigo and tinitus. Three patients presented with alerterd level of awarrness. Four patients developed very severe bilateral hearing impairment, whereas one endophtalmtis and one developed endocarditis. The cerebrospinal fluid (CSF) was opalescent in four patients, and only one patient presented with clear CSF. CSF examination showed typical changes characteristic for bacterial meningitis. Streptoccocus suis was isolated in CSF in all patients, and in one patient the bacteria was isolated in blood as well. All patients underwent treatement with II and III generation cephalosporins and one with one aminoglycosides. All patients were cured, but 4 of them developed sequelae like permanent sensorineural deafness and mild ataxia. CONCLUSIONS: Streptococcus suis infection is present as a zoonosis in pigs, while humans are contracted occasionaly, most frequently related to occupational risk. In cases with bacterial meningitis with sepsis and hearing loss, Streptococcus suis infections must be suspected. Effective prevention requires collaboration between epidemiologists, veterinarians and human medicine physicians.

Adult↗

Identification of an inducible bacteriophage in a virulent strain of Streptococcus suis serotype 2.

Streptococcus suis infection is considered to be a major problem in the swine industry worldwide. Most virulent Canadian isolates of S. suis serotype 2 do not produce the known virulence markers for this pathogen. PCR-based subtraction hybridization was adapted to isolate unique DNA sequences which were specific to virulent strains of S. suis isolated in Canada. Analysis of some subtracted DNA clones revealed significant homology with bacteriophages of gram-positive bacteria. An inducible phage (named Ss1) was observed in S. suis following the incubation of the virulent strain 89-999 with mitomycin C. Phage Ss1 has a long noncontractile tail and a small isometric nucleocapsid and is a member of the Siphoviridae family. Ss1 phage DNA appears to be present in most Canadian S. suis strains tested in this study, which were isolated from diseased pigs or had proven virulence in mouse or pig models. To our knowledge, this is the first report of the isolation of a phage in S. suis.

Animals↗

Cloning and partial characterization of the gene encoding the putative elongation factor Ts of Streptococcus suis serotype 2.

Streptococcus suis infection has a substantial impact on the swine industry. In addition, S. suis serotype 2 is recognized as a zoonotic agent. In this paper, we report the cloning and complete sequence of the gene coding for the putative elongation factor Ts ( tsf-like) of S. suis. The putative tsf gene seems to be transcribed from a promoter located within the cloned DNA fragment, as its expression is not dependent on insertional orientation within the plasmid. One copy of the tsf gene was detected in the chromosome of S. suis by Southern blot analysis. Interestingly, the elongation factor Ts expressed by all reference strains of all S. suis serotypes were antigenically similar, as determined by Western blot.

Antibodies, Bacterial↗

Invasion of porcine brain microvascular endothelial cells by Streptococcus suis serotype 2.

Streptococcus suis is an important swine pathogen that mainly causes meningitis and occasionally causes other infections, such as endocarditis, arthritis, and pneumonia. The pathogenesis of S. suis infection has not been completely defined. However, in order to cause meningitis, S. suis has to cross the blood-brain barrier (BBB) made up of brain microvascular endothelial cells. The objective of this work was to study the interactions of S. suis serotype 2 with porcine brain microvascular endothelial cells (PBMEC). The ability of North American and European S. suis serotype 2 strains to adhere to PBMEC and, most importantly, to invade PBMEC was demonstrated by using an antibiotic protection assay and was confirmed by electron microscopy. The polysaccharide capsule of S. suis seemed to partially interfere with the adhesion and invasion abilities of the bacterium. Our results showed that intracellular viable S. suis could be found in PBMEC up to 7 h after antibiotic treatment. Inhibition studies demonstrated that invasion of PBMEC by S. suis required actin microfilaments but not microtubular cytoskeletal elements or active bacterial RNA or protein synthesis. At high bacterial doses, suilysin-positive strains were toxic for PBMEC. The role of suilysin in cytotoxicity was confirmed by using purified suilysin, electron microscopy, and the lack of toxicity of a suilysin-negative mutant. In swine, the invasion of endothelial cells of the BBB could play an important role in the pathogenesis of the meningitis caused by S. suis.

Actin Cytoskeleton↗

Pro-inflammatory cytokine and chemokine release by human brain microvascular endothelial cells stimulated by Streptococcus suis serotype 2.

Streptococcus suis serotype 2 is a world-wide agent of diseases among pigs including meningitis, septicemia and arthritis. This microorganism is also recognized as an important zoonotic agent. The pathogenesis of the meningitis caused by S. suis is poorly understood. We have previously shown that S. suis is able to adhere to human brain microvascular endothelial cells (BMEC), but not to human umbilical vein endothelial cells (HUVEC). The objective of this work was to study the ability of S. suis serotype 2 to induce the release of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1); IL-6 and the chemokines IL-8 and monocyte chemotactic protein-1 (MCP-1) by human BMEC and HUVEC, using a sandwich enzyme-linked immunosorbent assay. S. suis was able to stimulate the production of IL-6, IL-8 and MCP-1 by BMEC but not HUVEC, in a time- and concentration-dependent manner. Bacterial cell wall components were largely responsible for such stimulation. The human and pig origin of strains does not seem to affect the intensity of the response; indeed, a very heterogeneous pattern of cytokine and chemokine production was observed for the different strains tested in this study. In situ production of cytokines and chemokines by BMEC may be the result of specific adhesion of S. suis to this cell type, with several consequences such as increased recruitment of leukocytes and an increase in the blood-brain barrier permeability.

Brain↗

Distribution, genetic diversity, and variable expression of the gene encoding hyaluronate lyase within the Streptococcus suis population.

Although Streptococcus suis is an economically important pathogen of pigs and an occasional cause of zoonotic infections of humans knowledge of crucial virulence factors, and as a consequence targets for therapeutic or prophylactic intervention, remains limited. Here we describe a detailed study of the distribution, diversity, and in vitro expression of hyaluronate lyase, a protein implicated as a virulence factor of many mucosal pathogens. The gene encoding hyaluronate lyase, hyl, was present in all 309 bona fide S. suis isolates examined representing diverse serotypes, geographic sources, and clinical backgrounds. Examination of the genetic diversity of hyl by RFLP and sequence analysis indicated a pattern of diversity shared by many gram-positive surface proteins with a variable 5' region encoding the most distal cell surface-exposed regions of the protein and a much more conserved 3' region encoding domains more closely associated with the bacterial cell. Variation occurs by several mechanisms, including the accumulation of point mutations and deletion and insertion events, and there is clear evidence that genetic recombination has contributed to molecular variation in this gene. Despite the ubiquitous presence of hyl, the corresponding enzyme activity was detected in fewer than 30% of the 309 isolates. In several cases this lack of activity correlates with the presence of mutations (either sequence duplications or point mutations) within hyl that result in a truncated polypeptide. There is a striking absence of hyaluronate lyase activity in a large majority of isolates from classic S. suis invasive disease, indicating that this protein is probably not a crucial virulence factor, although activity is present in significantly higher numbers of isolates associated with pneumonia.

Animals↗

Up-regulation of ICAM-1, CD11a/CD18 and CD11c/CD18 on human THP-1 monocytes stimulated by Streptococcus suis serotype 2.

Streptococcus suis serotype 2 is known to be a major pathogen of swine, causing mainly meningitis. It is also a zoonotic agent leading predominantly to meningitis in humans working in close contact with pigs. In this study, we investigated the ability of S. suis to up-regulate the expression of adhesion molecules involved in inflammation, using an enzyme-linked immunosorbent assay. S. suis serotype 2 stimulated the up-regulation of the expression of intercellular adhesion molecule-1 (ICAM-1, CD54), CD11a/CD18 and CD11c/CD18 on human THP-1 monocytes, but did not change that of ICAM-1, vascular cell adhesion molecule-1 (VCAM-1, CD106) and E-selectin (CD62E) on human endothelial cells. The up-regulation of adhesion molecules was time- and bacterial concentration-dependent, and cell wall components were largely responsible for such stimulation. To a lesser extent, purified haemolysin of S. suis also stimulated adhesion molecule expression. Stimulation of monocytes with strains of different origin showed that there was no clear tendency for human strains to induce a higher expression of adhesion molecules than strains from diseased pigs. Finally, monocytes stimulated with S. suis also showed an increase in adherence to endothelial cells. Hence, S. suis is capable of up-regulating important adhesion molecules involved in inflammation, which may result in an increased leucocyte recruitment into sites of infection, thus providing a possible mechanism for some of the inflammatory features of meningitis caused by this pathogen.

Antigens, CD↗

Production and properties of bacteriocin-like inhibitory substances from the swine pathogen Streptococcus suis serotype 2.

Streptococcus suis serotype 2 is a major pathogen found in the upper respiratory tract of swine. In this study, isolates of this bacterial species were tested for the production of bacteriocin-like inhibitory substances (BLIS). Of the 38 strains tested, four inhibited the growth of other S. suis isolates according to a deferred-antagonism plate assay. Interestingly, three of the strains were originally isolated from healthy carrier pigs and were considered nonvirulent. Three isolates (94-623, 90-1330, and AAH4) that produced BLIS in liquid broth were selected for further characterization. None of the inhibitory activities was related to the production of either organic acids or hydrogen peroxide. The BLIS produced by these strains were heat stable and proteinase K, pronase, and elastase sensitive but were trypsin and chymotrypsin resistant. They were stable at pH 2 and 12 and had molecular masses in the range of 14 to 30 kDa. Maximum production was observed during the mid-log phase. Following a curing procedure with novobiocin, only 90-1330 lost the ability to produce BLIS, suggesting that the BLIS might be plasmid encoded. Analysis of the inhibitory spectra revealed that the BLIS-producing strains also inhibited the growth of Actinobacillus minor, Actinobacillus porcinus, Enterococcus durans, Micrococcus luteus, Streptococcus agalactiae, Streptococcus dysgalactiae subsp. dysgalactiae, Streptococcus equi subsp. zooepidemicus, and S. dysgalactiae subsp. equisimilis. This study reports for the first time the ability of the swine pathogen S. suis serotype 2 to produce BLIS with the characteristics of classic bacteriocins. Further studies are required to investigate the possibility of using bacteriocin-producing strains to prevent swine infections caused by virulent strains of S. suis serotype 2.

Animals↗

Streptococcus suis meningitis, a poacher's risk.

Streptococcus suis infection is a zoonosis that has been mainly reported in pig-rearing and pork-consuming countries. The most common disease manifestation is meningitis, often associated with cochleovestibular signs. The causative agent is Streptococcus suis serotype 2, found as a commensal in the tonsils of its natural host, the pig. Persons at risk are mostly those with an occupational exposure to domestic pigs or their meat products. A case of meningitis caused by Streptococcus suis in a poacher who had killed and butchered a wild boar is reported. It appears that wild boar hunters are at additional risk of contracting the disease.

Animals↗

The pathogenesis of the meningitis caused by Streptococcus suis: the unresolved questions.

Streptococcus suis is one of the most important swine pathogens world-wide. Among the serotypes described, type 2 is the serotype most frequently associated with disease. Despite increasing research in recent years, knowledge of virulence factors and the pathogenesis of the infection remain limited. This review discusses the currently available information on S. suis serotype 2 virulence factors and the pathogenesis of the meningitis caused by this important bacterial species. In addition, some hypotheses on the critical steps of the infection, such as bacterial invasion from mucosal surfaces to the bloodstream, survival of bacteria in blood, and invasion from blood into the central nervous system, are presented. Finally, the role that the stimulation of the immune system of animals (inflammatory reaction) could play during infection is also discussed. A complete understanding of the cell-interacting pathways that S. suis may follow inside the host could give important insights into the progression of disease. Further studies to delineate the mechanisms through which S. suis induces meningitis will contribute to the development of potential therapies for S. suis infections.

Animals↗

Streptococcal toxic shock syndrome caused by Streptococcus suis serotype 2.

BACKGROUND: Streptococcus suis serotype 2 (S. suis 2, SS2) is a major zoonotic pathogen that causes only sporadic cases of meningitis and sepsis in humans. Most if not all cases of Streptococcal toxic shock syndrome (STSS) that have been well-documented to date were associated with the non-SS2 group A streptococcus (GAS). However, a recent large-scale outbreak of SS2 in Sichuan Province, China, appeared to be caused by more invasive deep-tissue infection with STSS, characterized by acute high fever, vascular collapse, hypotension, shock, and multiple organ failure. METHODS AND FINDINGS: We investigated this outbreak of SS2 infections in both human and pigs, which took place from July to August, 2005, through clinical observation and laboratory experiments. Clinical and pathological characterization of the human patients revealed the hallmarks of typical STSS, which to date had only been associated with GAS infection. Retrospectively, we found that this outbreak was very similar to an earlier outbreak in Jiangsu Province, China, in 1998. We isolated and analyzed 37 bacterial strains from human specimens and eight from pig specimens of the recent outbreak, as well as three human isolates and two pig isolates from the 1998 outbreak we had kept in our laboratory. The bacterial isolates were examined using light microscopy observation, pig infection experiments, multiplex-PCR assay, as well as restriction fragment length polymorphisms (RFLP) and multiple sequence alignment analyses. Multiple lines of evidence confirmed that highly virulent strains of SS2 were the causative agents of both outbreaks. CONCLUSIONS: We report, to our knowledge for the first time, two outbreaks of STSS caused by SS2, a non-GAS streptococcus. The 2005 outbreak was associated with 38 deaths out of 204 documented human cases; the 1998 outbreak with 14 deaths out of 25 reported human cases. Most of the fatal cases were characterized by STSS; some of them by meningitis or severe septicemia. The molecular mechanisms underlying these human STSS outbreaks in human beings remain unclear and an objective for further study.

Adult↗

Role of capsular sialic acid in virulence and resistance to phagocytosis of Streptococcus suis capsular type 2.

Streptococcus suis capsular type 2 has a capsule rich in sialic acid (NANA). Sialic acid, known to be an antiphagocytic factor for many bacterial species, inhibits the activation of the alternative complement pathway. The role of capsular NANA in virulence, resistance to phagocytosis and intracellular survival of S. suis capsular type 2 was evaluated. In general, a low concentration of NANA was observed for all the S. suis strains tested. In addition, no difference could be found in NANA concentrations between strains of different virulence degrees. Sialic acid concentration increased in the virulent strain 89-1591 and the avirulent strain 90-1330 after in vivo growth with an increased capsular material thickness compared to growth in vitro. No significant difference could be found in the phagocytosis rate by porcine blood monocytes of either strain and strain 89-1591 treated with sialidase or the sialic acid-binding lectin from Sambucus nigra (SNA I). Intracellular survival of strain 89-1591 decreased after treatments with sialidase or lectin, becoming comparable to that of strain 90-1330. Finally, no difference could be seen in virulence using a murine model, even if strain 89-1591 was treated with the enzyme or the lectin. Thus, NANA does not seem to be a critical virulence factor for S. suis capsular type 2.

Animals↗