Contamination of Streptococcus suis and S. suis Serotype 2 in Raw Pork and Edible Pig Organs: A Public Health Concern in Chiang Mai, Thailand.

Streptococcus suis is one of the most important zoonotic pathogens causing serious diseases in both pigs and humans, especially serotype 2. In northern Thailand, there is a notable prevalence of S. suis infection in humans and transmission has occurred mainly through the consumption of raw pork products. Despite the continued practice of consuming raw pork in this region, limited data exist regarding S. suis contamination in such products. Therefore, this study aimed to assess the prevalence of S. suis and S. suis serotype 2 in retail raw pork meat and edible pig organs sold in Chiang Mai city, Thailand. A total of 200 samples, comprising raw pork meat and edible pig organs, were collected from nine fresh markets in Chiang Mai city between May and July 2023. Samples were prepared and cultured in Todd-Hewitt broth. Bacterial DNA was extracted and tested for any serotypes of S. suis and serotype 2 using loop-mediated isothermal amplification (LAMP) techniques. The study revealed contaminations of S. suis and serotype 2 at rates of 84% and 34%, respectively, with a higher prevalence observed in pig organs compared to raw pork. Both S. suis and serotype 2 were detected across all nine fresh markets investigated. The prevalence of S. suis remained consistently high throughout the study period, whereas serotype 2 showed peaks in May and July. These high rates of contamination indicate that people who consume or work in close contact with raw pork or edible pig organs are at a high risk of S. suis infection. Urgent implementation and maintenance of food safety campaigns and public health interventions are crucial for disease prevention and control.

Near coding-complete genome sequence of 12 dengue serotype 2 viruses from the 2023 outbreak in Bangladesh.

We report the near coding-complete genomes of 12 DENV serotype 2 strains collected during the 2023 dengue outbreak in Bangladesh. Analyses showed that all 12 strains were closely related and belonged to genotype II-Cosmopolitan.

Concurrent infection of dengue virus with malaria parasites among outpatients attending healthcare facilities in Benin city, Nigeria.

Background: Dengue virus (DENV) and malaria parasites (MP) are among the common febrile diseases affecting the tropics and subtropics of the world. Both are mosquito-borne pathogens affecting humans and other animals. Methods: Blood samples were collected from 280 consented out-patients attending the selected hospitals and were analyzed. Malaria parasites were detected using microscopy and Malaria Ag Pf/Pan Rapid Test Device. Dengue virus was detected by serology and heminested reverse transcriptase PCR (hnRT-PCR) to target the flavivirus polymerase (NS5) gene. Results: Malaria parasites recorded a total positivity of 151 patients (53.9%) using microscopy, while DENV antibodies (DENV IgM and DENV IgG) were positive in 16 (5.7%) and 39 (13.9%) patients, respectively. There was a concurrent infection between MP/DENV IgM in 13 (4.6%) patients and MP/DENV IgG in 27 (9.6%) patients. Molecular identification revealed DENV serotype 2 in circulation. Conclusion: This study documents molecular evidence of dengue virus coexisting with malaria parasites in the study population, hence the need for efficient surveillance and control system.

Prevalence of Streptococcus suis serotype 2 isolated from pigs: A systematic review and meta-analysis.

Background and Aim: Among Streptococcus suis serotypes, S. suis serotype 2 is the most significant serotype that causes serious diseases in pigs and humans worldwide. The present study aimed to estimate the global prevalence of S. suis serotype 2 isolated from pigs, determine its trend, and explore the factors associated with this serotype. Materials and Methods: We retrieved relevant published studies from PubMed, Scopus, and the Web of Science. The retrieved citations were screened for possible inclusion. Relevant data were then extracted from the included studies. The random-effects model was used for all meta-analyses. A subgroup meta-analysis was used to assess the heterogeneity of the prevalence for four characteristics (continents, sampling organs, reporting unit, and pig's health status). A cumulative meta-analysis was performed to determine the cumulative prevalence over time. Meta-regression analysis was used to determine the trend of pooled prevalence of S. suis serotype 2 over time. Results: Of 600 articles retrieved, 36 studies comprising a total sample size of 6939 isolates or samples from 16 countries of four continents were included for meta-analysis. The pooled prevalence of S. suis serotype 2 isolated from pigs was 13.6% (95% confidence interval [CI], 10.7%-17.1%), with high heterogeneity among the included studies (Cochran's Q, 431.6; p < 0.001; I2 = 91.9%; Table-1). No statistical significance was observed among subgroups of the four characteristics examined. However, the pooled prevalence of S. suis serotype 2 was as high as 16.0% (95% CI, 12.5%-20.3%; n = 16) in diseased pigs compared with 9.9% (95% CI, 5.6%-17.0%; n = 15) in healthy pigs. The pooled prevalence of S. suis serotype 2 isolated from pigs did not significantly decrease over time [regression coefficient = -0.020 (95% CI, 0.046-0.006, p = 0.139)]. The pooled prevalence of S. suis serotype 2 isolated from pigs fluctuated slightly between 13.2% and 17.8% from 2007 to 2023, although the pooled prevalence gradually decreased from 30.6% in 1987 to over 20% in 2003. Conclusion: The global prevalence of S. suis serotype 2 isolated from pigs was estimated to be 13.6% (approximately 10% in healthy pigs and around 16% in diseased pigs). S. suis serotype 2 isolated from pigs did not change significantly over time. These results indicate that S. suis serotype 2 remains a problem for the pig industry and poses a threat to human health.

Persistence of dengue serotype 2 viral RNA in blood cells of a returned traveler with dengue fever.

Dengue virus (DENV) is one of the most significant vector-borne pathogens worldwide. In this report, we describe clinical features and laboratory detection of dengue in a 45-year-old traveler to Nicaragua on return home to the United States in 2019. Clinical presentation was mild, with rash, headache, and fatigue, with only low-grade transient fever. Infection dynamics were documented by serology and PCR of serially collected body fluids. DENV serotype 2 was detected in whole blood 1 day after symptoms emerged, with viral RNA isolated to the red cell fraction, and remained detectable through day 89. DENV-2 RNA was detected in serum only on day 4, and IgM was undetectable on day 4 but evident by day 13. Viral RNA was also detected in urine. This report of DENV-2 RNA persistence in blood cells but only transient appearance in serum, supports the potential diagnostic value of whole blood over serum for PCR and opportunity of an expanded testing window. Informed testing approaches can improve diagnostic accuracy and inform strategies that preserve individual and public health.

Reemergence of Sylvatic Dengue Virus Serotype 2 in Kedougou, Senegal, 2020.

In 2020, a sylvatic dengue virus serotype 2 infection outbreak resulted in 59 confirmed dengue cases in Kedougou, Senegal, suggesting those strains might not require adaptation to reemerge into urban transmission cycles. Large-scale genomic surveillance and updated molecular diagnostic tools are needed to effectively prevent dengue virus infections in Senegal.

Enolase of Streptococcus suis serotype 2 promotes biomolecular condensation of ribosomal protein SA for HBMECs apoptosis.

BACKGROUND: Ribosomal protein SA (RPSA) of human brain microvascular endothelial cells (HBMECs) can transfer from the cytosol to the cell surface and act as a receptor for some pathogens, including Streptococcus suis serotype 2 (SS2), a zoonotic pathogen causing meningitis in pigs and humans. We previously reported that SS2 virulence factor enolase (ENO) binds to RPSA on the cell surface of HBMECs and induces apoptosis. However, the mechanism that activates RPSA translocation to the cell surface and induces ENO-mediated HBMEC apoptosis is unclear. RESULTS: Here, we show that RPSA localization and condensation on the host cell surface depend on its internally disordered region (IDR). ENO binds to the IDR of RPSA and promotes its interaction with RPSA and vimentin (VIM), which is significantly suppressed after 1,6-Hexanediol (1,6-Hex, a widely used tool to disrupt phase separation) treatment, indicating that ENO incorporation and thus the concentration of RPSA/VIM complexes via co-condensation. Furthermore, increasing intracellular calcium ions (Ca2+) in response to SS2 infection further facilitates the liquid-like condensation of RPSA and aggravates ENO-induced HBMEC cell apoptosis. CONCLUSIONS: Together, our study provides a previously underappreciated molecular mechanism illuminating that ENO-induced RPSA condensation activates the migration of RPSA to the bacterial cell surface and stimulates SS2-infected HBMEC death and, potentially, disease progression. This study offers a fresh avenue for investigation into the mechanism by which other harmful bacteria infect hosts via cell surfaces' RPSA.

Detection of a Multiple Circulation Event of Dengue Virus 2 Strains in the Northern Region of Brazil.

Dengue virus serotype 2 (DENV-2) is responsible for dengue epidemics on a global scale and is associated with severe cases of the disease. This study conducted a phylogenetic investigation of DENV-2 isolates from 2017 to 2021 originating from the northern states of Brazil. A total of 32 samples from DENV-2 isolates were analyzed, including 12 from Acre, 19 from Roraima, and one from Tocantins. Only one lineage of the Asian-American genotype and one lineage of the cosmopolitan genotype were observed: Lineage 1, Asian-American genotype (connection to Puerto Rico); Lineage 5, cosmopolitan genotype (connection to Peru). Our results provide important data regarding the study of DENV genotypes and lineage distribution and open up possibilities for probable introduction and dissemination routes.

O-acetyl-homoserine sulfhydrylase deficient Streptococcus suis serotype 2 strain SC19 becomes an avirulent strain and provides immune protection against homotype infection in mice.

O-acetyl-homoserine sulfhydrylase (OAHS) is a pyridoxal 5'-phosphate-dependent enzyme involved in microbial methionine biosynthesis, which catalyzes the conversion of o-acetyl-homoserine (OAH) to homocysteine. In our previous study, we found that OAHS of Streptococcus suis serotype 2 (SS2) can interact with the porcine blood-brain barrier (BBB) model, but whether OAHS regulates the penetration of BBB during SS2 infection is still unclear. To explore the role of OAHS in SS2 infection, OAHS-deficient SS2 mutant strain (SC19-ΔOAHS) and gene complemental strain (SC19-cΔOAHS) were constructed. Compared to the parent strain, with the loss of oahs, the chain length of SC19-ΔOAHS was shortened, the virulence was significantly reduced, the survival rate of mice infected with SC19-ΔOAHS was obviously increased accompanied by the relieved clinical symptoms. And the survival ability of SC19-ΔOAHS in whole blood was also remarkably decreased. Interestingly, the adhesion of SC19-ΔOAHS to endothelial cells was markedly increased, but the deficiency of OAHS significantly inhibited the strain penetrating BBB both in vivo and in vitro. Most of these phenomena can be reversed by the complemental strain (SC19-cΔOAHS). Further study showed that the deficiency of OAHS severely reduced SC19-induced endothelial cell apoptosis, tight junctions (TJs) protein impairment and the expression of SS2 virulence factor Enolase (Eno), involved in the destruction of BBB. Additionally, SC19-ΔOAHS immunized mice were able to resist SC19 or JZLQ022 infection. In conclusion, we confirmed that OAHS promoted the pathogenicity by enhancing host's BBB permeability and immune escape, and SC19- ΔOAHS is a potential live vaccine.

Study of the Role of Lipoprotein Maturation Enzymes in the Pathogenesis of the Infection Caused by the Streptococcus suis Serotype 2 Sequence Type 25 North American Prototype Strain.

Streptococcus suis serotype 2 is an important swine bacterial pathogen causing sudden death, septic shock, and meningitis. However, serotype 2 strains are phenotypically and genotypically heterogeneous and composed of a multitude of sequence types (STs) whose distributions greatly vary worldwide. It has been previously shown that the lipoprotein (LPP) maturation enzymes diacylglyceryl transferase (Lgt) and signal peptidase (Lsp) significantly modulate the inflammatory host response and play a differential role in virulence depending on the genetic background of the strain. Differently from Eurasian ST1/ST7 strains, the capsular polysaccharide of a North American S. suis serotype 2 ST25 representative strain only partially masks sub-capsular domains and bacterial wall components. Thus, our hypothesis is that since LPPs would be more surface exposed in ST25 strains than in their ST1 or ST7 counterparts, the maturation enzymes would play a more important role in the pathogenesis of the infection caused by the North American strain. Using isogenic Δlgt and Δlsp mutants derived from the wild-type ST25 strain, our studies suggest that these enzymes do not seem to play a role in the interaction between S. suis and epithelial and endothelial cells, regardless of the genetics background of the strain used. However, a role in the formation of biofilms (also independently of the STs) has been demonstrated. Moreover, the involvement of LPP dendritic cell activation in vitro seems to be somehow more pronounced with the ST25 strain. Finally, the Lgt enzyme seems to play a more important role in the virulence of the ST25 strain. Although some differences between STs could be observed, our original hypothesis that LPPs would be significantly more important in ST25 strains due to a better bacterial surface exposition could not be confirmed.

Ratiometric electrochemical lateral flow immunoassay for the detection of Streptococcus suis serotype 2.

An electrochemical lateral flow immunoassay (eLFIA) strip with high reproducibility was developed to rapidly and accurately detect Streptococcus suis serotype 2. This proposed strip was fabricated by integrating ratiometric electrochemical detection and LFIA (R-eLFIA). The R-eLFIA exhibited excellent reproducibility, which was improved by 3.8 times compared to a single electrode. A dual-working screen-printed graphene electrode (SPGE) was designed by tuning the working electrode with electroactive species in the biosensing system. Ferrocene carboxylic acid (Fc) was used as a signal probe, and sunset yellow (SY) at one working electrode was used as an internal reference signal to provide a built-in correction for reducing the effects of inherent background current. S. suis serotype 2-specific antibodies were immobilized on a nitrocellulose membrane of LFIA, which is located on the position of Fc-SPGE. In the presence of the analyte, an immunocomplex formed on the region of Fc-SPGE, causing a decrease in Fc current while SY current remained constant. The current ratio's decrease was proportional to S. suis serotype 2's concentration. Under optimization, this biosensor showed good linearity in the range of 102-1010 CFU/mL with a limit of detection of 10 CFU/mL and achieved a rapid detection time (15 min). Moreover, the R-eLFIA biosensor exhibited excellent reproducibility and high selectivity and was applied in human serum samples. Thus, this study successfully matched the advantages of the ratiometric strategy and LFIA and has great potential to be used as an effective tool for rapidly detecting S. suis serotype 2 in clinical samples.

Reemergence of Cosmopolitan Genotype Dengue Virus Serotype 2, Southern Vietnam.

We performed phylogenetic analysis on dengue virus serotype 2 Cosmopolitan genotype in Ho Chi Minh City, Vietnam. We document virus emergence, probable routes of introduction, and timeline of events. Our findings highlight the need for continuous, systematic genomic surveillance to manage outbreaks and forecast future epidemics.

Liang-Ge-San inhibits dengue virus serotype 2 infection by reducing caveolin1-induced cytoplasmic heat shock protein 70 translocation into the plasma membrane.

BACKGROUND: Dengue virus (DENV) is a major public health threat. However, there are no specific therapeutic drugs for DENV. Many Chinese heat-cleaning formulas, such as Liang-Ge-San (LGS), have been frequently used in the virus-induced diseases. The antiviral effect of LGS has not been reported yet. PURPOSE: In this study, the effect of LGS on the inhibition of dengue virus serotype 2 (DENV-2) was investigated and the relevant mechanism was explored. METHODS: High-performance liquid chromatography was applied to analyze the chemical characterization of LGS. The in vitro antiviral activities of LGS against DENV-2 were evaluated by time-of-drug-addition assay. The binding of heat shock protein 70 (Hsp70) and envelope (E) protein or caveolin1 (Cav1) were analyzed by immunofluorescence and immunoprecipitation assays. Then the role of Cav1 in the anti-DENV-2 effects of LGS was further examined. DENV-2 infected Institute of Cancer Research suckling mice (n = 10) and AG129 mice (n = 8) were used to examine the protective effects of LGS. RESULTS: It was found that geniposide, liquiritin, forsythenside A, forsythin, baicalin, baicalein, rhein, and emodin maybe the characteristic components of LGS. LGS inhibited the early stage of DENV-2 infection, decreased the expression levels of viral E and non-structural protein 1 (NS1) proteins. LGS also reduced E protein and Hsp70 binding and attenuated the translocation of Hsp70 from cytoplasm to the cell membrane. Moreover, LGS decreased the binding of Hsp70 to Cav1. Further study showed that the overexpression of Cav1 reversed LGS-mediated E protein and Hsp70 inhibition in the plasma membrane. In the in vivo study, LGS was highly effective in prolonging the survival time, reducing viral loads. CONCLUSION: This work demonstrates for the first time that LGS exerts anti-DENV-2 activity in vitro and in vivo. LGS decreases DENV-2-stimulated cytoplasmic Hsp70 translocation into the plasma membrane by Cav1 inhibition, thereby inhibiting the early stage of virus infection. These findings indicate that LGS may be a candidate for the treatment of DENV.

Emergence of a New Strain of DENV-2 in South America: Introduction of the Cosmopolitan Genotype through the Brazilian-Peruvian Border.

Dengue virus 2 (DENV-2) seriously contributes to dengue-related mortality. It includes five nonsylvatic genotypes, with cosmopolitan being the most widespread with a significant contribution to the total number of DENV-2 cases globally. In South America, the cosmopolitan genotype was first recorded in 2019 in Madre de Dios, Peru, and then in Goiás (Midwest Brazil) in November 2021. In this study, we tested 163 human serum samples from Acre (Northern Brazil) collected during a DENV outbreak between 2020 and 2021 for all DENV genotypes by RT-qPCR. Of the 163 samples, 139 were positive for DENV-2, and 5 were positive for DENV-1. Five DENV-2-positive samples from early 2021 were sequenced, and the sequences clustered with the three other DENV-2 cosmopolitan genotype sequences already recorded on the continent. These results create a geographical link, suggesting the possible route of introduction of the DENV-2 cosmopolitan genotype into Brazil through the border with Peru, from which it may have dispersed to Midwest Brazil.

Thioredoxin A of Streptococcus suis Serotype 2 Contributes to Virulence by Inhibiting the Expression of Pentraxin 3 to Promote Survival Within Macrophages.

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that can infect humans in contact with infected pigs or their byproducts. It can employ different types of genes to defend against oxidative stress and ensure its survival. The thioredoxin (Trx) system is a key antioxidant system that contributes adversity adaptation and pathogenicity. SS2 has been shown to encode putative thioredoxin genes, but the biological roles, coding sequence, and underlying mechanisms remains uncharacterized. Here, we demonstrated that SSU05_0237-ORF, from a clinical SS2 strain, ZJ081101, encodes a protein of 104 amino acids with a canonical CGPC active motif and an identity 70-85% similar to the thioredoxin A (TrxA) in other microorganisms. Recombinant TrxA efficiently catalyzed the thiol-disulfide oxidoreduction of insulin. The deletion of TrxA led to a significantly slow growth and markedly compromised tolerance of the pathogen to temperature stress, as well as impaired adhesion ability to pig intestinal epithelial cells (IPEC-J2). However, it was not involved in H2O2 and paraquat-induced oxidative stress. Compared with the wild-type strain, the ΔTrxA strain was more susceptible to killing by macrophages through increasing NO production. Treatment with TrxA mutant strain also significantly attenuated cytotoxic effects on RAW 264.7 cells by inhibiting inflammatory response and apoptosis. Knockdown of pentraxin 3 in RAW 264.7 cells was more vulnerable to phagocytic activity, and TrxA promoted SS2 survival in phagocytic cells depending on pentraxin 3 activity compared with the wild-type strain. Moreover, a co-inoculation experiment in mice revealed that TrxA mutant strain is far more easily cleared from the body than the wild type strain in the period from 8-24 h, and exhibits significantly attenuated oxidative stress and liver injury. In summary, we reveal the important role of TrxA in the pathogenesis of SS2.

Vimentin affects inflammation and neutrophil recruitment in airway epithelium during Streptococcus suis serotype 2 infection.

Streptococcus suis serotype 2 (SS2) frequently colonizes the swine upper respiratory tract and can cause Streptococcal disease in swine with clinical manifestations of pneumonia, meningitis, and septicemia. Previously, we have shown that vimentin, a kind of intermediate filament protein, is involved in the penetration of SS2 through the tracheal epithelial barrier. The initiation of invasive disease is closely related to SS2-induced excessive local inflammation; however, the role of vimentin in airway epithelial inflammation remains unclear. Here, we show that vimentin deficient mice exhibit attenuated lung injury, diminished production of proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and the IL-8 homolog, keratinocyte-derived chemokine (KC), and substantially reduced neutrophils in the lungs following intranasal infection with SS2. We also found that swine tracheal epithelial cells (STEC) without vimentin show decreased transcription of IL-6, TNF-α, and IL-8. SS2 infection caused reassembly of vimentin in STEC, and pharmacological disruption of vimentin filaments prevented the transcription of those proinflammatory cytokines. Furthermore, deficiency of vimentin failed to increase the transcription of nucleotide oligomerization domain protein 2 (NOD2), which is known to interact with vimentin, and the phosphorylation of NF-κB protein p65. This study provides insights into how vimentin promotes excessive airway inflammation, thereby exacerbating airway injury and SS2-induced systemic infection.

Molecular characterization of recombinant premembrane protein of dengue virus serotype-2 for development of diagnostic assay.

Dengue is an acute arboviral infection common in tropical and subtropical countries. Dengue has been highlighted as a public health concern in the last five decades, affecting almost 50% of the population in developing nations. Dengue infection results in a complex symptomatic disease that ranges from headache, fever, and skin rash to extreme hemorrhage fever and liver dysfunction. The diagnosis of the disease is essential for effective treatment. The early onset of the infection can be detected through viral structural peptides that act as markers for detection, including Pre-Membrane (Pre-M) protein. In the currently proposed research, the structural gene obtained from local isolates was targeted for studies. For this purpose, recombinant structural protein Pre-M was amplified, cloned, and expressed in the bacterial expression system. The expression of the structural protein (Pre-M) was scrutinized by Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) and validated by western blot and dot blot, and afterwards, the antigen was purified. The purified Pre-M protein carries the potential for the development of in-house diagnostic assay as well as for vaccine production. This study aimed to develop a highly specific, sensitive, and cost-effective in-house enzyme-linked immunoassay (ELISA) for the detection of antibodies of Pakistani most prevalent dengue virus serotype 2 (DENV-2). The success of this research would also pave the way toward developing novel vaccines for the future prevention of dengue infection.

Multiple introductions and country-wide spread of DENV-2 genotype II (Cosmopolitan) in Brazil.

Dengue virus serotype 2, genotype Cosmopolitan (DENV-2-GII), is one of the most widespread DENV strains globally. In the USA, DENV-2 epidemics have been dominated by DENV-2 genotype Asian-American (DENV-2-GIII), and the first cases of DENV-2-GII were only described in 2019, in Peru, and in 2021 in Brazil. To gain new information about the circulation of DENV-2-GII in Brazil, we sequenced 237 DENV-2 confirmed cases sampled between March 2021 and March 2023 and revealed that DENV-2-GII is already present in all geographic regions of Brazil. The phylogeographic analysis inferred that DENV-2-GII was introduced at least four times in Brazil, between May 2020 and August 2022, generating multiple clades that spread throughout the country with different success. Despite multiple introductions of DENV-2-GII, analysis of the country-wide laboratory surveillance data showed that the Brazilian dengue epidemic in 2022 was dominated by DENV-1 in most states. We hypothesize that massive circulation of DENV-2-GIII in previous years in Brazil might have created a population immune barrier against symptomatic homotypic reinfections by DENV-2-GII, leading to sustained cryptic circulation in asymptomatic cases and localized outbreaks of this new genotype. In summary, our study stresses the importance of arboviral genomic surveillance to close monitoring and better understanding the potential impact of DENV-2-GII in the coming years.

A Comprehensive Study to Unleash the Putative Inhibitors of Serotype2 of Dengue Virus: Insights from an In Silico Structure-Based Drug Discovery.

Dengue fever is a mosquito-borne disease that claims the lives of millions of people around the world. A number of factors like disease's non-specific symptoms, increased viral mutation, growing antiviral drug resistance due to reduced susceptibility, unavailability of an effective vaccine for dengue, weak immunity against the virus, and many more are involved. Dengue belongs to the Flaviviridae family of viruses. The two species of the vector transmitting dengue are Aedes aegypti and Aedes albopictus, with the former one being dominant. Serotypes 2 of dengue fever are spread to the human body and cause severe illness. Recently, dengue has imposed an aggressive effect synergistically with the COVID-19 pandemic. As a result, we concentrated our efforts on finding a potential therapeutic. For this, we chose natural compounds to fight dengue fever, which is currently regarded as successful among many drug therapies. Following this, we started the in silico experiment with 922 plant extracts as lead compounds to fight serotype 2. In this study, we used SwissADME for analyzing ligand drug-likeness, pkCSM for designing an ADMET profile, Autodock vina 4.2 and Swissdock tools for molecular docking, and finally Desmond for molecular dynamics simulation. Ultimately 45 were found effective against the 2'O methyltransferase protein of serotype 2. CHEMBL376820 was found as possible therapeutic candidates for inhibiting methyltransferase protein in this thorough analysis. Nevertheless, more in vitro and in vivo research are required to substantiate their potential therapeutic efficacy.

IL-18 Signaling Is Essential for Causing Streptococcal Toxic Shock-like Syndrome (STSLS).

Streptococcus suis (S. suis) is an emerging zoonotic pathogen that can cause multiple diseases, including streptococcal toxic shock-like syndrome (STSLS). The S. suis SC-19 strain could cause NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome hyperactivation, then induce a cytokine storm and STSLS. Although IL-18 is the downstream effector of NLRP3 signaling, the role of IL-18 signaling on STSLS remains to be elucidated. Thus, il18r1 gene knockout mice were constructed and challenged with the SC-19 strain. Alleviated clinical signs and tissue damages, as well as improved survival were observed in il18r-/- mice compared with the WT mice post-SC-19 challenge. Meanwhile, an obvious decrease in the inflammatory cytokine levels in blood was observed in the il18r-/- mice infected with SC-19. Therefore, IL-18, the downstream effector of NLRP3 inflammasome activation, was responsible for the cytokine storm and STSLS development caused by S. suis, suggesting that IL-18/IL-18Rα signaling could serve as a new target for STSLS.