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Veterinary Research Nov 2022Streptococcus suis is a zoonotic agent that causes sepsis and meningitis in pigs and humans. S. suis infections are responsible for large economic losses in pig... (Review)
Review
Streptococcus suis is a zoonotic agent that causes sepsis and meningitis in pigs and humans. S. suis infections are responsible for large economic losses in pig production. The lack of effective vaccines to prevent the disease has promoted the extensive use of antibiotics worldwide. This has been followed by the emergence of resistance against different classes of antibiotics. The rates of resistance to tetracyclines, lincosamides, and macrolides are extremely high, and resistance has spread worldwide. The genetic origin of S. suis resistance is multiple and includes the production of target-modifying and antibiotic-inactivating enzymes and mutations in antibiotic targets. S. suis genomes contain traits of horizontal gene transfer. Many mobile genetic elements carry a variety of genes that confer resistance to antibiotics as well as genes for autonomous DNA transfer and, thus, S. suis can rapidly acquire multiresistance. In addition, S. suis forms microcolonies on host tissues, which are associations of microorganisms that generate tolerance to antibiotics through a variety of mechanisms and favor the exchange of genetic material. Thus, alternatives to currently used antibiotics are highly demanded. A deep understanding of the mechanisms by which S. suis becomes resistant or tolerant to antibiotics may help to develop novel molecules or combinations of antimicrobials to fight these infections. Meanwhile, phage therapy and vaccination are promising alternative strategies, which could alleviate disease pressure and, thereby, antibiotic use.
Topics: Humans; Swine; Animals; Streptococcus suis; Streptococcal Infections; Anti-Bacterial Agents; Macrolides; Swine Diseases
PubMed: 36371221
DOI: 10.1186/s13567-022-01111-3 -
Current Issues in Molecular Biology 2019() is an important zoonotic pathogen that causes huge economic losses in the pig industry, as well as severe illness and even death in humans. The outbreak of human... (Review)
Review
() is an important zoonotic pathogen that causes huge economic losses in the pig industry, as well as severe illness and even death in humans. The outbreak of human infection of in China in 2005 led to significant human morbidity and death, prompting an increase in global studies of . In recent years, important advances have been made regarding the etiology, genomics, excavation of virulence genes, and vaccine research in . A number of countries and regions have identified their predominantly serotypes. The development of genome sequencing technology has laid an important foundation for the study of pathogenic mechanisms. For example, 89K PAI was found in representative virulence strains in China, and several studies have been carried out to confirm multiple genes which carries are closely related to virulence. Also, the functions of some regulatory genes represented by the two-component signal transduction system have been analyzed. The development of inactivated vaccines, natural avirulent vaccines, gene-deletion attenuated vaccines, subunit vaccines, and glycoconjugate vaccines have greatly contributed to the prevention and control of the disease in the future. This article aims to summarize the research progress to provide directions for future research and the prevention of .
Topics: Animals; China; Disease Outbreaks; Gene Expression Regulation, Bacterial; Gene Regulatory Networks; Genes, Bacterial; Genome, Bacterial; Humans; Prevalence; Signal Transduction; Streptococcal Infections; Streptococcal Vaccines; Streptococcus suis; Swine; Swine Diseases; Vaccines, Attenuated; Vaccines, Subunit; Virulence
PubMed: 31166178
DOI: 10.21775/cimb.032.473 -
Microbiology Spectrum Jun 2023Streptococcus suis is an recognized zoonotic pathogen of swine and severely threatens human health. Zinc is the second most abundant transition metal in biological...
Streptococcus suis is an recognized zoonotic pathogen of swine and severely threatens human health. Zinc is the second most abundant transition metal in biological systems. Here, we investigated the contribution of zinc to the drug resistance and pathogenesis of S. suis. We knocked out the genes of AdcACB and Lmb, two Zn-binding lipoproteins. Compared to the wild-type strain, we found that the survival rate of this double-mutant strain (ΔΔ) was reduced in Zinc-limited medium, but not in Zinc-supplemented medium. Additionally, phenotypic experiments showed that the ΔΔ strain displayed impaired adhesion to and invasion of cells, biofilm formation, and tolerance of cell envelope-targeting antibiotics. In a murine infection model, deletion of the and genes in S. suis resulted in a significant decrease in strain virulence, including survival rate, tissue bacterial load, inflammatory cytokine levels, and histopathological damage. These findings show that AdcA and Lmb are important for biofilm formation, drug resistance, and virulence in S. suis. Transition metals are important micronutrients for bacterial growth. Zn is necessary for the catalytic activity and structural integrity of various metalloproteins involved in bacterial pathogenic processes. However, how these invaders adapt to host-imposed metal starvation and overcome nutritional immunity remains unknown. Thus, pathogenic bacteria must acquire Zn during infection in order to successfully survive and multiply. The host uses nutritional immunity to limit the uptake of Zn by the invading bacteria. The bacterium uses a set of high-affinity Zn uptake systems to overcome this host metal restriction. Here, we identified two Zn uptake transporters in S. suis, AdcA and Lmb, by bioinformatics analysis and found that an and double-mutant strain could not grow in Zn-deficient medium and was more sensitive to cell envelope-targeting antibiotics. It is worth noting that the Zn uptake system is essential for biofilm formation, drug resistance, and virulence in S. suis. The Zn uptake system is expected to be a target for the development of novel antimicrobial therapies.
Topics: Animals; Humans; Mice; Bacterial Proteins; Drug Resistance; Streptococcus suis; Swine; Virulence; Zinc
PubMed: 37212676
DOI: 10.1128/spectrum.04337-22 -
Canadian Journal of Veterinary Research... Oct 2023and are ubiquitous colonizers of swine tonsils that can cause systemic disease and death, under undefined conditions. It is not known, however, whether these 2 species...
and are ubiquitous colonizers of swine tonsils that can cause systemic disease and death, under undefined conditions. It is not known, however, whether these 2 species interact during initial infection. To investigate whether such interactions occur, the objective of this study was to assess phenotypic differences between mono-and co-cultures of and when representative strains with different virulence potential were co-cultured In cross-streak screening experiments, some (GP) serovar strains (GP3, GP4, GP5) exhibited altered morphology with some (SS) serovar strains, such as SS2, but not with SS1. Co-culture with GP5 reduced hemolytic activity of SS1, but not of SS2. Although both SS strains outgrew GP isolates in biofilm co-cultures, strain type affected the number of planktonic or sessile cells in co-culture biofilms. Numbers of sessile SS1 increased in co-cultures, but not of GP3. Both planktonic and sessile SS2 increased in co-culture, whereas GP5 decreased. Sessile SS1 increased, but planktonic GP5 decreased in co-culture and planktonic SS2 increased, but sessile GP3 decreased when grown together. The SS2 strain had a competitive advantage over GP3 during mid-exponential co-culture in broth. is predicted to use more unique carbon sources, suggesting that outcompetes in growth and nutrient consumption. This work provides direction for future studies of phenotypic and genotypic interactions between these and other swine tonsil co-colonizers.
Topics: Animals; Swine; Streptococcus suis; Coculture Techniques; Serogroup; Virulence; Genotype; Swine Diseases; Streptococcal Infections
PubMed: 37790267
DOI: No ID Found -
Emerging Microbes & Infections Dec 2024is a major bacterial pathogen in pigs and an emerging zoonotic pathogen. Different serotypes exhibit diverse characteristics in population structure and pathogenicity....
is a major bacterial pathogen in pigs and an emerging zoonotic pathogen. Different serotypes exhibit diverse characteristics in population structure and pathogenicity. Surveillance data highlight the significance of serotype 4 (SS4) in swine streptococcusis, a pathotype causing human infections. However, except for a few epidemiologic studies, the information on SS4 remains limited. In this study, we investigated the population structure, pathogenicity, and antimicrobial characteristics of SS4 based on 126 isolates, including one from a patient with septicemia. We discovered significant diversities within this population, clustering into six minimum core genome (MCG) groups (1, 2, 3, 4, 7-2, and 7-3) and five lineages. Two main clonal complexes (CCs), CC17 and CC94, belong to MCG groups 1 and 3, respectively. Numerous important putative virulence-associated genes are present in these two MCG groups, and 35.00% (7/20) of pig isolates from CC17, CC94, and CC839 (also belonging to MCG group 3) were highly virulent (mortality rate ≥ 80%) in zebrafish and mice, similar to the human isolate ID36054. Cytotoxicity assays showed that the human and pig isolates of SS4 strains exhibit significant cytotoxicity to human cells. Antimicrobial susceptibility testing showed that 95.83% of strains isolated from our labs were classified as multidrug-resistant. Prophages were identified as the primary vehicle for antibiotic resistance genes. Our study demonstrates the public health threat posed by SS4, expanding the understanding of SS4 population structure and pathogenicity characteristics and providing valuable information for its surveillance and prevention.
Topics: Streptococcus suis; Animals; Swine; Humans; Streptococcal Infections; Serogroup; Swine Diseases; Virulence; Mice; Genome, Bacterial; Zebrafish; Anti-Bacterial Agents; Phylogeny; Microbial Sensitivity Tests; Virulence Factors
PubMed: 38703011
DOI: 10.1080/22221751.2024.2352435 -
Microbiology Spectrum Aug 2022Streptococcus suis is an important zoonotic bacterial pathogen posing a threat to the pig industry as well as public health, for which the mechanisms of growth and cell...
Streptococcus suis is an important zoonotic bacterial pathogen posing a threat to the pig industry as well as public health, for which the mechanisms of growth and cell division remain largely unknown. Developing convenient genetic tools that can achieve strictly controlled gene expression is of great value for investigating these fundamental physiological processes of S. suis. In this study, we first identified three strong constitutive promoters, P, P, and P, in S. suis. Promoter P was used to drive the expression of repressor genes and , and the operator sequences were added within promoters P and P. By optimizing the insertion sites of the operator sequence, we successfully constructed an anhydrotetracycline (ATc)-inducible expression system and an isopropyl-β-d-thiogalactopyranoside (IPTG)-inducible expression system in S. suis. We showed that these two systems provided inducer-concentration- and induction-time-dependent expression of the reporter gene. By using these tools, we investigated the subcellular localization of a key cell division protein, FtsZ, which showed that it could be correctly localized to the midcell region. In addition, we constructed a conditional knockout strain for the gene, which is an essential gene, and showed that our ATc-inducible promoter could provide strictly controlled expression of in , suggesting that our inducible expression systems can be used for deletion of essential genes in S. suis. Therefore, for the first time we developed two inducible expression systems in S. suis and showed their applications in the study of an important cell division protein and an essential gene. These genetic tools will further facilitate the functional study of other important genes of S. suis. Streptococcus suis is an important zoonotic bacterial pathogen. Studying the mechanisms of cell growth and division is important for the identification of novel antimicrobial drug targets. Inducible expression systems can provide strictly controlled expression of the protein of interest and are useful tools to study the functions of physiologically important proteins. However, there is a lack of convenient genetic tools that can achieve inducible protein expression in S. suis. In this study, we developed two (ATc-inducible and IPTG-inducible) inducible expression systems and showed their applications in a subcellular localization study of a cell division protein and the construction of conditional knockout of essential genes in S. suis. These systems will be useful for functional studies of important proteins of S. suis.
Topics: Animals; Bacterial Proteins; Base Sequence; Cell Division; Isopropyl Thiogalactoside; Promoter Regions, Genetic; Streptococcus suis; Swine
PubMed: 35758678
DOI: 10.1128/spectrum.00363-22 -
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 -
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 -
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 -
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