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Journal of Applied Microbiology Mar 2021Streptococcus suis is a highly zoonotic pathogen that is a serious threat to human health and the development of the pig industry worldwide. The virulence factors...
AIMS
Streptococcus suis is a highly zoonotic pathogen that is a serious threat to human health and the development of the pig industry worldwide. The virulence factors produced during S. suis infection play an important role, and the pore-forming activity of suilysin is considered an important virulence-related factor, especially in meningitis. Treatment of S. suis infection with traditional antibiotics is becoming increasingly challenging due to bacterial resistance. The purpose of this study is to verify the role of cryptotanshinone in the process of S. suis infection and provide a new drug precursor for the treatment of S. suis infection.
METHODS AND RESULTS
In this study, we used circular dichroism spectroscopy to demonstrate that cryptotanshinone alters the secondary structure of suilysin. The results of the antibacterial activity and haemolysis assays showed cryptotanshinone could inhibit the pore-forming activity of suilysin without affecting bacterial growth or its expression. We also showed that cryptotanshinone reduces bacterial damage and penetration in vitro, reduce the S. suis-induced inflammatory response and provide protection against bacterial infections in vivo and in vitro.
CONCLUSIONS
Cryptotanshinone is a potential compound precursor for treating S. suis infection.
SIGNIFICANCE AND IMPACT OF THE STUDY
Cryptotanshinone may be a promising leading compound for S. suis infection and related diseases.
Topics: Animals; Anti-Bacterial Agents; Hemolysin Proteins; Hemolysis; Humans; Inflammation; Mice; Phenanthrenes; Protein Structure, Secondary; Streptococcal Infections; Streptococcus suis; Virulence; Virulence Factors
PubMed: 32750224
DOI: 10.1111/jam.14810 -
Acta Veterinaria Scandinavica Jun 2020Streptococcus suis is a major cause of meningitis, arthritis, and pneumonia in pigs worldwide, and an emerging pathogen in humans. In Sweden, S. suis has previously...
BACKGROUND
Streptococcus suis is a major cause of meningitis, arthritis, and pneumonia in pigs worldwide, and an emerging pathogen in humans. In Sweden, S. suis has previously received little attention but has in recent years become increasingly recognized as affecting the pig production. The aim of the present study was to investigate the occurrence, serotypes and antimicrobial susceptibility of S. suis in Swedish grower pigs from herds with and without reported S. suis associated disease, as well as possible associations between S. suis associated disease and selected environmental and production factors. Swab samples were taken from the tonsils of clinically healthy 8-13-week-old grower pigs from ten case herds and ten control herds. Isolates were cultured, identified using MALDI-TOF MS, and serotyped using latex agglutination. The antimicrobial susceptibility of 188 isolates was tested using broth microdilution. Production data was gathered and environmental parameters were measured on the farms.
RESULTS
Streptococcus suis was isolated from 95% of the sampled pigs in both the case and the control herds. Serotypes 3, 4, 5, 7, 9, 10, 11, 15, 16, and 17-34 were detected, although a majority of the isolates (81.5%) were non-typeable. There was less diversity among the serotypes isolated from the case herds than among those from the control herds; four and nine different serotypes, respectively. Isolates resistant to penicillin (3.8%) were reported for the first time in Sweden. Tetracycline resistance was common (88.4%). No association was noted between the production and the environmental factors investigated, and the carriership of S. suis.
CONCLUSIONS
The carriership of S. suis was found to be higher in clinically healthy Swedish pigs than previously estimated, and for the first time, the presence of Swedish isolates resistant to penicillin was reported. Many of the most commonly disease-associated serotypes, e.g. serotypes 2, 9, 3, and 7, were detected in healthy grower pigs although further studies are needed to investigate the virulence of these isolates.
Topics: Animals; Anti-Bacterial Agents; Female; Incidence; Microbial Sensitivity Tests; Serogroup; Streptococcal Infections; Streptococcus suis; Sus scrofa; Sweden; Swine; Swine Diseases
PubMed: 32580735
DOI: 10.1186/s13028-020-00533-3 -
PLoS Pathogens Mar 2023GntR transcription factor of Streptococcus suis serotype 2 (SS2) is a potential substrate protein of STK, but the regulation mechanisms of GntR phosphorylation are still...
GntR transcription factor of Streptococcus suis serotype 2 (SS2) is a potential substrate protein of STK, but the regulation mechanisms of GntR phosphorylation are still unclear. This study confirmed that STK phosphorylated GntR in vivo, and in vitro phosphorylation experiments showed that STK phosphorylated GntR at Ser-41. The phosphomimetic strain (GntR-S41E) had significantly reduced lethality in mice and reduced bacterial load in the blood, lung, liver, spleen, and brain of infected mice compared to wild-type (WT) SS2. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) experiments demonstrated that the promoter of nox was bound by GntR. The phosphomimetic protein GntR-S41E cannot bind to the promoter of nox, and the nox transcription levels were significantly reduced in the GntR-S41E mutant compared to WT SS2. The virulence in mice and the ability to resist oxidative stress of the GntR-S41E strain were restored by complementing transcript levels of nox. NOX is an NADH oxidase that catalyzes the oxidation of NADH to NAD+ with the reduction of oxygen to water. We found that NADH is likely accumulated under oxidative stress in the GntR-S41E strain, and higher NADH levels resulted in increased amplified ROS killing. In total, we report GntR phosphorylation could inhibit the transcription of nox, which impaired the ability of SS2 to resist oxidative stress and virulence.
Topics: Animals; Mice; Virulence; Streptococcus suis; Phosphorylation; NAD; Oxidative Stress; Streptococcal Infections; Bacterial Proteins
PubMed: 36913374
DOI: 10.1371/journal.ppat.1011227 -
Methods in Molecular Biology (Clifton,... 2024Streptococcus suis is a swine bacterial pathogen that predominantly causes disease in weaned piglets characterized by swelling of joints, arthritis, septicemia,...
Streptococcus suis is a swine bacterial pathogen that predominantly causes disease in weaned piglets characterized by swelling of joints, arthritis, septicemia, meningitis, and sudden death. Intravenous, intramuscular, intraperitoneal, and intranasal infection models were developed to study the bacterial pathogenicity and efficacy of vaccines and various therapeutics. The selection of the appropriate infection model is a critical step in any study, as it may impact the outcomes of the study. Here we describe a method for infecting weaned piglets with S. suis using intraperitoneal route as a reliable, consistent, and reproducible animal model to evaluate vaccine protection against systemic bacterial infection.
Topics: Animals; Swine; Disease Models, Animal; Streptococcus suis; Streptococcal Infections; Swine Diseases; Injections, Intraperitoneal
PubMed: 38884914
DOI: 10.1007/978-1-0716-3898-9_9 -
MSphere Mar 2021Bacteria of different shapes have adopted distinct mechanisms to faithfully coordinate morphogenesis and segregate their chromosomes prior to cell division. Despite...
Bacteria of different shapes have adopted distinct mechanisms to faithfully coordinate morphogenesis and segregate their chromosomes prior to cell division. Despite recent focuses and advances, the mechanism of cell division in ovococci remains largely unknown. , a major zoonotic pathogen that causes problems in human health and in the global swine industry, is an elongated and ellipsoid bacterium that undergoes successive parallel splitting perpendicular to its long axis. Studies on cell cycle processes in this bacterium are limited. Here, we report that MsmK (ultiple ugar etabolism protein ), an ATPase that contributes to the transport of multiple carbohydrates, has a novel role as a cell division protein in MsmK can display ATPase and GTPase activities, interact with FtsZ via the N terminus of MsmK, and promote the bundling of FtsZ protofilaments in a GTP-dependent manner Deletion of the C-terminal region or the Walker A or B motif affects the affinity between MsmK and FtsZ and decreases the ability of MsmK to promote FtsZ protofilament bundling. MsmK can form a complex with FtsZ , and its absence is not lethal but results in long chains and short, occasionally anuclear daughter cells. Superresolution microscopy revealed that the lack of MsmK in cells leads to normal septal peptidoglycan walls in mother cells but disturbed cell elongation and peripheral peptidoglycan synthesis. In summary, MsmK is a novel cell division protein that maintains cell shape and is involved in the synthesis of the peripheral cell wall. Bacterial cell division is a highly ordered process regulated in time and space and is a potential target for the development of antimicrobial drugs. Bacteria of distinct shapes depend on different cell division mechanisms, but the mechanisms used by ovococci remain largely unknown. Here, we focused on the zoonotic pathogen and identified a novel cell division protein named MsmK, which acts as an ATPase of the ATP-binding cassette-type carbohydrate transport system. MsmK has GTPase and ATPase activities. protein assays showed that MsmK interacts with FtsZ and promotes FtsZ protofilament bundling that relies on GTP. Superresolution microscopy revealed that MsmK maintains cell shape and is involved in peripheral peptidoglycan synthesis. Knowledge of the multiple functions of MsmK may broaden our understanding of known cell division processes. Further studies in this area will elucidate how bacteria can faithfully and continually multiply in a constantly changing environment.
Topics: Adenosine Triphosphatases; Bacterial Proteins; Biological Transport; Carbohydrate Metabolism; Cell Division; Cell Wall; Cytoskeletal Proteins; Phosphorylation; Streptococcus suis
PubMed: 33731468
DOI: 10.1128/mSphere.00119-21 -
MicrobiologyOpen Oct 2021Streptococcus suis, an emerging zoonotic pathogen, causes invasive diseases in pigs, including sepsis, meningitis, endocarditis, pneumonia, and arthritis. Importantly,...
Streptococcus suis, an emerging zoonotic pathogen, causes invasive diseases in pigs, including sepsis, meningitis, endocarditis, pneumonia, and arthritis. Importantly, similar pathologies are reported in human S. suis infections. In previous work, the locus SSU0375 of S. suis strain P1.7 had been identified as a conditionally essential gene by intrathecal experimental infection of pigs with a transposon library of S. suis. This study aimed to identify the function of the corresponding gene product. Bioinformatics analysis and homology modeling revealed sequence and structural homologies with the Streptococcus pneumoniae mid-cell-anchored protein Z (MapZ) that is involved in cell division in different bacterial species. Indeed, depletion of this locus in S. suis strain 10 revealed a growth defect as compared to the wild type. Electron microscopy analysis of the corresponding mutant demonstrated morphological growth defects as compared to the wild-type strain, including an irregular cell shape and size as well as mispositioned division septa. Light microscopy and subsequent quantitative image analysis confirmed these morphological alterations. In the genetic rescue strain, the wild-type phenotype was completely restored. In summary, we proposed that SSU0375 or the corresponding locus in strain 10 encode for a S. suis MapZ homolog that guides septum positioning as evidenced for other members of the Streptococci family.
Topics: Animals; Bacterial Proteins; Cell Division; Computational Biology; Cytokinesis; Genes, Essential; Humans; Mutation; Streptococcal Infections; Streptococcus pneumoniae; Streptococcus suis
PubMed: 34713609
DOI: 10.1002/mbo3.1234 -
Advances in Microbial Physiology 2021Streptococcus suis is a major cause of respiratory tract and invasive infections in pigs and is responsible for a substantial disease burden in the pig industry. S. suis... (Review)
Review
Streptococcus suis is a major cause of respiratory tract and invasive infections in pigs and is responsible for a substantial disease burden in the pig industry. S. suis is also a significant cause of bacterial meningitis in humans, particularly in South East Asia. S. suis expresses a wide array of virulence factors, and although many are described as being required for disease, no single factor has been demonstrated to be absolutely required. The lack of uniform distribution of known virulence factors among individual strains and lack of evidence that any particular virulence factor is essential for disease makes the development of vaccines and treatments challenging. Here we review the current understanding of S. suis virulence factors and their role in the pathogenesis of this important zoonotic pathogen.
Topics: Animals; Life Style; Streptococcal Infections; Streptococcus suis; Swine; Swine Diseases; Virulence; Virulence Factors
PubMed: 34147186
DOI: 10.1016/bs.ampbs.2020.12.002 -
Applied and Environmental Microbiology Dec 2018, an important zoonotic pathogen, has caused considerable economic losses in the swine industry and severe public health issues worldwide. The development of a novel...
, an important zoonotic pathogen, has caused considerable economic losses in the swine industry and severe public health issues worldwide. The development of a novel effective strategy for the prevention and therapy of is urgently needed. Here, amentoflavone, a natural biflavonoid compound isolated from Chinese herbs that has negligible anti- activity, was identified as a potent antagonist of suilysin (SLY)-mediated hemolysis without interfering with the expression of SLY. Amentoflavone effectively inhibited SLY oligomerization, which is critical for its pore-forming activity. The treatment with amentoflavone reduced -induced cytotoxicity in macrophages (J774 cells). Furthermore, -infected mice that received amentoflavone exhibited lower mortality and bacterial burden. Additionally, amentoflavone significantly decreased the production of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 in an -infected cell model. Analyses of signaling pathways demonstrated that amentoflavone reduced -induced inflammation in serotype 2 (SS2)-infected cells by regulating the p38, Jun N-terminal protein kinase 1 and 2 (JNK1/2), and NF-κB pathways. The antivirulence and anti-inflammatory properties of amentoflavone against infection provide the possibility for future pharmaceutical application of amentoflavone in the treatment of infection. The widespread use of antibiotics in therapy and in the prevention of infection in the swine industry raises concerns for the emergence of a resistant strain. The use of antivirulence agents has potential benefits, mainly because of the reduced selective pressure for the development of bacterial resistance. In this study, we found that amentoflavone is an effective agent against serotype 2 (SS2) infection both and Our results demonstrated that amentoflavone is a promising anti-infective therapeutic for infections, due to its antivirulence and anti-inflammatory effects without antibacterial activity, with fewer side effects than conventional antibacterial agents.
Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Biflavonoids; Cell Line; Disease Models, Animal; Drugs, Chinese Herbal; Female; Hemolysin Proteins; Hemolysis; Inflammation; Interleukin-1beta; Interleukin-6; Macrophages; Metabolic Networks and Pathways; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Mitogen-Activated Protein Kinase 8; Mitogen-Activated Protein Kinase 9; NF-kappa B; Serogroup; Streptococcal Infections; Streptococcus suis; Swine; Swine Diseases; Tumor Necrosis Factor-alpha; Virulence
PubMed: 30315078
DOI: 10.1128/AEM.01804-18 -
Trends in Microbiology Jul 2017Streptococcus suis is an important swine pathogen that can be transmitted to humans by contact with diseased animals or contaminated raw pork products. This pathogen... (Review)
Review
Streptococcus suis is an important swine pathogen that can be transmitted to humans by contact with diseased animals or contaminated raw pork products. This pathogen possesses a coat of capsular polysaccharide (CPS) that confers protection against the immune system. Yet, the CPS is not the only virulence factor enabling this bacterium to successfully colonize, invade, and disseminate in its host leading to severe systemic diseases such as meningitis and toxic shock-like syndrome. Indeed, recent research developments, cautiously inventoried in this review, have revealed over 100 'putative virulence factors or traits' (surface-associated or secreted components, regulatory genes or metabolic pathways), of which at least 37 have been claimed as being 'critical' for virulence. In this review we discuss the current contradictions and controversies raised by this explosion of virulence factors and the future directions that may be conceived to advance and enlighten research on S. suis pathogenesis.
Topics: Animals; Disease Models, Animal; Humans; Mutagenesis; Polysaccharides, Bacterial; Red Meat; Streptococcal Infections; Streptococcus suis; Swine; Virulence; Virulence Factors
PubMed: 28274524
DOI: 10.1016/j.tim.2017.02.005 -
Veterinary Microbiology Aug 2021Streptococcus suis is a zoonotic pathogen that can cause invasive infections in humans and pigs. The S. suis cps31 strains (SS31) were frequently isolated from healthy...
Streptococcus suis is a zoonotic pathogen that can cause invasive infections in humans and pigs. The S. suis cps31 strains (SS31) were frequently isolated from healthy or diseased pigs and one human infection case caused by SS31 was reported in Thailand in 2015. However, except for a few epidemiologic studies, little information is available for SS31. To characterize SS31, a total of 75 SS31 strains were analyzed, including 52 strains that were isolated from healthy or diseased pigs and 23 strains whose information was accessed from NCBI. The MLST analysis showed that SS31 exhibited high heterogeneity. The phylogenetic analysis and minimum core-genome (MCG) classification revealed that 75 strains were clustered into 3 lineages. Strains from NCBI mainly at Lineage 2 belong to MCG7-3, and most of strains from China at Lineage 3 belong to MCG7-2. This finding indicated that their evolutionary path was different. All SS31 strains were resistant to more than three classes of antimicrobial agents, and major antimicrobial resistance genes for strains from Lineage 3 were carried by prophages. This observation is different from the previous observation that integrative conjugative elements and integrative and mobilizable elements are major vehicles of antimicrobial resistance genes for S. suis. In addition to strains isolated from diseased pigs, seven of 47 strains isolated from clinically healthy pigs were also pathogenic in a zebrafish infection model. These findings reveal unique characteristics of SS31 and contribute to establishing public health surveillance for SS31 and clarifying the diversity of S. suis.
Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Evolution, Molecular; Genotype; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Multilocus Sequence Typing; Phylogeny; Streptococcal Infections; Streptococcus suis; Swine; Swine Diseases; Virulence; Zebrafish
PubMed: 34147764
DOI: 10.1016/j.vetmic.2021.109149