Group A Streptococcus Research Articles

Recombinational exchange of M-fibril and T-pilus genes generates extensive cell surface diversity in the global group A Streptococcus population.

Among genes present in all group A streptococci (GAS), those encoding M-fibril and T-pilus proteins display the highest levels of sequence diversity, giving rise to the two primary serological typing schemes historically used to define strain. A new genotyping scheme for the pilin adhesin and backbone genes is developed and, when combined with emm typing, provides an account of the global GAS strain population. Cluster analysis based on nucleotide sequence similarity assigns most T-serotypes to discrete pilin backbone sequence clusters, yet the established T-types correspond to only half the clusters. The major pilin adhesin and backbone sequence clusters yield 98 unique combinations, defined as "pilin types." Numerous horizontal transfer events that involve pilin or emm genes generate extensive antigenic and functional diversity on the bacterial cell surface and lead to the emergence of new strains. Inferred pilin genotypes applied to a meta-analysis of global population-based collections of pharyngitis and impetigo isolates reveal highly significant associations between pilin genotypes and GAS infection at distinct ecological niches, consistent with a role for pilin gene products in adaptive evolution. Integration of emm and pilin typing into open-access online tools (pubmlst.org) ensures broad utility for end-users wanting to determine the architecture of M-fibril and T-pilus genes from genome assemblies.IMPORTANCEPrecision in defining the variant forms of infectious agents is critical to understanding their population biology and the epidemiology of associated diseases. Group A Streptococcus (GAS) is a global pathogen that causes a wide range of diseases and displays a highly diverse cell surface due to the antigenic heterogeneity of M-fibril and T-pilus proteins which also act as virulence factors of varied functions. emm genotyping is well-established and highly utilized, but there is no counterpart for pilin genes. A global GAS collection provides the basis for a comprehensive pilin typing scheme, and online tools for determining emm and pilin genotypes are developed. Application of these tools reveals the expansion of structural-functional diversity among GAS via horizontal gene transfer, as evidenced by unique combinations of surface protein genes. Pilin and emm genotype correlations with superficial throat vs skin infection provide new insights on the molecular determinants underlying key ecological and epidemiological trends.

Epidemiological changes of acute respiratory infections in children: A single-center experience after COVID-19 lockdown.

Since the start of the COVID-19 pandemic, the epidemiology of acute respiratory infections (ARIs) has continually changed, making it difficult to predict. Our study aimed to evaluate epidemiological changes and clinical outcomes of ARIs in pediatric patients in the post-lockdown period. A single-center retrospective cross-sectional study was performed in one of the largest pediatric emergency departments in Lithuania during two cold seasons-from October 1, 2021, to April 30, 2022 (Season I) and in the same period in 2022-2023 (Season II). Patients under 18 years of age who had been tested for COVID-19 were enrolled in the study. Additional data about other respiratory pathogens in the study group (specifically influenza A/B, respiratory syncytial virus (RSV) and group A Streptococcus (GAS)), were included. During both seasons of our study, 19,366 children were screened for COVID-19. Positive tests for COVID-19 decreased from 14.5% in Season I to 5.9% in Season II, while at the same time, the rates of other infections increased significantly: influenza from 17.5% to 27.1%, RSV from 8.8% to 27.6%, and GAS from 8.4% to 44%, respectively. In Season II, COVID-19 infection presented in fewer admissions to pediatric intensive care (0.8% vs. 3.7%, p<0.01) and there were no deaths, while influenza presented in a higher proportion of hospitalizations (10.5% vs. 6.1%, p<0.01) and there was one death. The proportion of RSV hospitalizations also increased in Season II (34.6% vs. 44.0%, p<0.01). The early post-lockdown period saw a decline of COVID-19 and re-emergence of influenza, RSV and GAS infections in children. In Season II, COVID-19 cases became milder contrary to influenza. RSV infection contributed significantly to hospitalizations for respiratory infections in children in both seasons, particularly in Season II. Coinfections were not associated with a more severe course of the disease.

Efficacy of Alum-Adjuvanted Peptide and Carbohydrate Conjugate Vaccine Candidates against Group A Streptococcus Pharyngeal Infection in a Non-Human Primate Model.

Vaccine development against group A Streptococcus (GAS) has gained traction in the last decade, fuelled by recognition of the significant worldwide burden of the disease. Several vaccine candidates are currently being evaluated in preclinical and early clinical studies. Here, we investigate two conjugate vaccine candidates that have shown promise in mouse models of infection. Two antigens, the J8 peptide from the conserved C-terminal end of the M protein, and the group A carbohydrate lacking N-acetylglucosamine side chain (ΔGAC) were each conjugated to arginine deiminase (ADI), an anchorless surface protein from GAS. Both conjugate vaccine candidates combined with alum adjuvant were tested in a non-human primate (NHP) model of pharyngeal infection. High antibody titres were detected against J8 and ADI antigens, while high background antibody titres in NHP sera hindered accurate quantification of ΔGAC-specific antibodies. The severity of pharyngitis and tonsillitis signs, as well as the level of GAS colonisation, showed no significant differences in NHPs immunised with either conjugate vaccine candidate compared to NHPs in the negative control group.

Complicated pneumonia caused by group A Streptococcus in children - 2022/2023 infectious season outbreak and update on clinical characteristics

BackgroundAn increased incidence of group A Streptococcus (GAS) infections has been observed in pediatric population post-COVID-19 pandemic. While the majority of reports refer to scarlet fever or invasive GAS disease, detailed data on pulmonary manifestations such as complicated community-acquired pneumonia (CAP) are scarce. The aim of this study was to assess the contribution of GAS to complicated CAP in children during the 2022/2023 infectious season. MethodsWe retrospectively analyzed the etiology and clinical presentation of complicated CAP patients hospitalized in our tertiary care center in Warsaw, Poland, between August 2022 and May 2023. ResultsAmong 91 patients with complicated CAP, GAS was the dominant cause constituting 24.2% (22/91; 95% CI 15.8–34.3%) of the study group. 68.2% of GAS pneumonia patients presented symptoms of scarlet fever, and 27.3% had preceding or concurrent viral infection. GAS complicated CAP was associated with longer hospitalization, higher incidence of chest tube insertion, but shorter duration of chest tube drainage than complicated CAP of other etiology. Children with GAS complicated CAP had higher procalcitonin concentration (28.1 vs. 1.5 ng/dL; p<0.0001) and a lower platelets level (254.5 vs. 422 × 103/μL; p = 0.0031) than those with non-GAS infection. ConclusionsGAS is currently the predominant pathogen of complicated CAP in children. Clinicians should be aware of the current epidemiological situation and a more severe course of GAS pneumonia in this age group, and should monitor patients presenting with symptoms of scarlet fever and preceding viral infection closely.

Serological Diagnosis of Acute Tonsillitis in Salah Al-Din Province

Abstract Background: Tonsillitis is one of the most important diseases in the community, especially in children, but its complications can affect adults at any age. The most bacterial causative agent is group A streptococci (GAS) infections, like tonsillitis, can progress into rheumatic fever and lead to complications like heart, kidney, and joint damage, known as poststreptococcal diseases. In Iraq, rheumatism is diagnosed based on antistreptolysin O titer (ASO) antigen serological titers. Objectives: This study aimed to recognize ASO in patients who had tonsillitis in Salah Al-Din Province, Iraq, where information about the test was lacking. Materials and Methods: The cross-sectional study was conducted in Salah Al-Din Province, with 235 patients aged 5–45 years examined at the Primary Health Care Center. Blood samples were taken and examined for antistreptolysin O using turbidimetry. Results: The results showed that ASO tonsillitis often increases in early childhood and decreases in urban areas (32.5%) presenting fever, joint, and loin pain. Conclusion: In conclusion, 40% of patients with tonsillitis had elevated antistreptolysin O levels, especially in the 5–14 years age group (47.36%), in urban areas (32.5%), and associated with fever (42.1%), cough (24.2%), and loin with joint pain (33.6%). These cases may progress into rheumatic heart disease, therefore, prompt treatment is necessary. A plan to prevent GAS infection and its complications should be implemented, along with more sensitive and specific investigations.

Surge for narrow-spectrum antibiotics in times of the MDR crisis: Systematic literature review to establish the role of amoxicillin in tonsillopharyngitis

Background: Group A Streptococcus (GAS) is the predominant pathogen accountable for tonsillitis, making it the most prevalent and frequently encountered bacterial cause of upper respiratory infections. Although amoxicillin is a frequently prescribed antibiotic for the treatment of tonsillopharyngitis, alternate agents like macrolides are regularly recommended. The objective of this study was to evaluate and compare the effectiveness of amoxicillin, its side effects, and the associated risk ratio with alternative antibiotic treatments for respiratory tract infections and tonsillopharyngitis in both children and adults. Material and Methods: An initial search was performed via five basic databases PubMed, Medline, Embase, clinicaltrial.gov and the Cochrane Central Register of Controlled Trials, to identify studies meeting the inclusion criteria spanning from July 2012 to June 2023. The primary search of studies resulted in 6260 from four databases during the study period. Results: After the initial scan of titles and abstracts, 06 studies were included in the review, which reported clinical cure rates. Four out of six studies reported adverse events. Conclusion: Our analysis infers that given their narrow spectrum of activity, low incidence of side effects, comparable efficacy and cost-effectiveness, penicillin or amoxicillin can be considered as preferable choice for the management of tonsillopharyngitis and broad-spectrum antibiotics offer no added advantage in disease management. Keywords: Amoxicillin, Tonsillopharyngitis, Tonsillitis, Acute respiratory infection, Streptococcal infection, GAS, SLR, Systematic literature Review, Antibiotics

Emerging Clinical Features of Acute Mastoiditis in Israel: A Registry Based Cohort.

Acute mastoiditis (AM) is a severe infection in the young population, with possible life-threatening complications. This study aimed to characterize AM presentation, symptoms and signs, complications, and management, over a period of 10 years. This large-scale population-based cohort studied "Clalit Health Care" records, to include patients <18 years diagnosed with AM, hospitalized between the years 2008-2018. After validation, we investigated clinical symptoms and signs, pneumococcal vaccination status, complications, laboratory and microbiological parameters, imaging, antibiotic treatment and surgical interventions. AM was diagnosed in 1189 patients, mean age of 2.71 years and 591 (49.71%) were female. Most presented with protrusion of pinna (83.1%), retro auricular redness (73.5%) and fever (71.8%). Patients <2 years of age had more symptoms (3.8 ± 1.4, opposed to 3.6 ± 1.5, P = 0.006) and showed higher white blood cell count and C-reactive protein values. Local and intracranial complications occurred in 233 (20.8%) and 75 (6.5%) patients, respectively. Complications were associated with increased white blood cell count and C-reactive protein and related to bacterial type, specifically Fusobacterium necrophorum ( P < 0.0001), for which 50% had an intracranial complication. Between the years 2008-2018, Streptococcus pneumoniae -positive cultures decreased (30.9% to 10.3%, P > 0.0001) as opposed to group-A Streptococcus (10.9% to 30.9%, P = 0.002). This study shows a difference in AM appearance in the <2 years population and the association between white blood cell count, C-reactive protein and microbiology results with the occurrence of a complication. This may play a role in the management process, such as imaging and intervention needs. Although performed during the pneumococcal vaccine era, the disease microbiology was shown to change significantly throughout the study.

Determination of the upper limit of normal for serum anti-streptolysin-O titre in primary school children in Southern Nigeria; A model for other low resource settings

The prevention and treatment of Rheumatic Heart disease is hinged on antibiotic administration in children with Group A Streptococcal (GAS) pharyngitis and Acute Rheumatic Fever (ARF). The Upper Limit of Normal (ULN) for serum Anti-streptolysin O titre (ASOT) has been employed as proof of antecedent GAS pharyngitis to fulfil the Jones’ criteria for diagnosis of ARF. This value has not been generated among West African children. Generalization of values from Caucasians (200 IU/ml) is likely to result in over-diagnosis, owing to higher GAS pharyngitis incidence in Africa. We aimed to determine the serum ASOT and its ULN in apparently healthy school-aged children in Egor Local Government Area (LGA), south-south Nigeria and to determine their relationship with socio-demographic characteristics.We recruited 384 apparently healthy school-aged pupils across eleven schools. Serum ASOT was determined by turbidimetry. Statistical analysis was done using student's t-test and Analysis of Variance (ANOVA). Level of significance was set at p < 0.05.The mean age was 8.53 ± 1.97(range 6–12) years and male-female ratio was 1.1:1. The ULN and geometric mean serum ASOT were 390.76 IU/ml and 230.04 ± 1.86 IU/ml respectively. No significant correlation was found between serum ASOT and age (r-value of −4.8%). The ULN did not vary significantly with gender, socio-economic class and the presence/absence of over-crowding in homes. The ULN for serum ASOT in apparently healthy school-aged children in Egor LGA is higher than the currently used international value. Clinicians in West Africa should consider applying higher cut-off values for the diagnosis of ARF.

PRELIMINARY EVALUATION OF ANTIBIOTIC SUSCEPTIBILITY PATTERNS OF PATHOGENS ISOLATED FROM PRIVATE LABORATORY SPECIMENS IN UKRAINE

Objective. This study aims at conducting an analysis of data on antibiotic resistance to antimicrobials that were obtained for the period from April 28, 2018, to December 31, 2019, in a private laboratory in the city of Kharkiv. Materials and methods. We conducted an investigation into the identification and analysis of antimicrobial sensitivity for isolates obtained from patients at a private clinic in the city of Kharkiv from 2018 to 2019. Results. The analysis revealed that patients most frequently sought bacteriological examination for materials from the throat (34.5%) and nose (29.9%), while the least common requests were for examination of the mucous membrane of the oral cavity (2.3%) and skin (3.4%). The positive results accounted for 94.3% of the cases. The isolated strains included Staphylococcus aureus (29.4%), Neisseria spp. (16.5%), Staphylococcus epidermidis (14.1%), Streptococcus spp. of the Viridans group (12.9%), Candida albicans (5.9%), Moraxella spp. (1.2%), Streptococcus anhaemolyticus, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa (each constituting 3.5%), molds (2.4%), and Streptococcus haemolyticus, Enterobacter aerogenes, and Enterococcus faecalis (each accounting for 1.2%). The isolated strains obtained from patients of the private laboratory had a pronounced antibiotic resistance to antimicrobial drugs of the following groups: beta-lactams, tetracycline, aminoglycosides, and sulfonamides. This should be taken into account by doctors when prescribing antibacterial therapy. Conclusions. The data indicate disturbingly high levels of antimicrobial resistance in isolates collected from patients at a private clinic in the city of Kharkiv.

IMPACT OF A GEL COMPOSITION CONTAINING VARIOUS SUBSTANCES ON INDICES OF IMMUNITY AND TISSUE INFLAMMATION IN PALATINE TONSILS OF PATIENTS WITH CATARRHAL GINGIVITIS DURING CHRONIC TONSILLITIS

The study of pharmacotherapeutic (immunomodulating) action in conditions of in vitro cell cultures is currently considered appropriate and justified for determining the action of drugs at the preclinical level. It is also important to address the pathogenetic nature in using such agents, especially fro local application. This study investigated the efficacy of a multicomponent gel containing decamethoxine and hyaluronic acid in treating chronic catarrhal gingivitis among patients with chronic tonsillitis. The purpose of the work is to assess the efficacy of a gel containing decamethoxine and hyaluronic acid on the tissue of the palatine tonsils in the therapy of chronic catarrhal gingivitis in patients with chronic tonsillitis.&#x0D; Materials and methods. To investigate the effects of the main active components in the gel, we followed the recommendations of I.P. Kaidashev et al. for testing pharmacological preparations in in vitro cultures. Tissue samples from the palatine tonsils were obtained from 20 patients with chronic tonsillitis and chronic catarrhal gingivitis undergoing tonsillectomy. All procedures adhered to the guidelines set by the Laboratory of Pathophysiology and Immunology at Prof. O.S. Kolomiichenko Institute of Otolaryngology, National Academy of Sciences of Ukraine. Palatine tonsil tissue was incubated in 199 medium (Serva, Germany) containing gentamicin sulfate (Darnytsa, Ukraine) at a concentration of 120 μg/ml for 20 minutes at 4-8°C. After that, the hemorrhagic parts were removed from the whole tonsil and placed into Eagle's medium (Sigma, USA) and rinsed three to four times. Subsequently, the prepared tissue was placed in sterile vials containing enriched Eagle's medium supplemented with L-glutamine, sodium bicarbonate, 100x vitamin concentrate, 5% fetal calf serum, and 60 μg/mL gentamicin. Tonsil tissue was dissected using scissors and then washed repeatedly (5-7 times) with fresh medium to remove loosely attached cells, then, the resulting cell suspension was filtered. All procedures were conducted within a sterile laminar flow cabinet. Cell viability was assessed using light microscopy (Olympus-23, Japan) and a hemocytometer. A final cell suspension containing 2.5 million lymphocytes per milliliter of medium was prepared. Suspensions with a viability of less than 90% (blue, "dead" cells) were excluded from further experiments.&#x0D; Results. Treatment of in vitro palatine tonsil cells from patients with chronic catarrhal gingivitis and recurrent tonsillitis with the main components of the developed gel (decamethoxine and hyaluronic acid) did not induce significant changes in the concentration of α and γ-interferons. Our findings suggest that the gel composition reduces the levels of pro-inflammatory factors: interleukin-1β and immune complexes. Additionally, it appears to stimulate the production of the antimicrobial factor antistreptolysin-O by tonsil cells, potentially leading to increased antibody production against hemolytic streptococcus antigens.&#x0D; Conclusion. Based on the in vitro findings, the investigated gel composition containing decamethoxine and hyaluronic acid demonstrates potential anti-inflammatory and antimicrobial properties that stimulate the production of the antimicrobial factor antistreptolysin-O by tonsil cells, which might lead to increased antibody production against hemolytic streptococcus antigens.

MICROBIAL AIR POLLUTION IN POLTAVA

Regular monitoring of air quality indicators, including microbial composition, is crucial for public health and should be a cornerstone of national healthcare policy. However, existing scientific literature lacks comprehensive data on microbial air pollution in Ukraine, particularly in Poltava and its surrounding areas. This study aims to assess the level of microbial air pollution across various districts within Poltava city.&#x0D; Materials and methods. The Koch sedimentation method was used to assess the level of microbial air pollution in the districts of Poltava. For this purpose, atmospheric air sampling was taken in park zones of various districts in the city of Poltava during October 2023. For comparison, air samples were taken in deciduous and coniferous forests of villages adjacent to the city. According to the results of cultivation, the total microbial count (TCM) of the air in 1 m3 of each sample was calculated separately.&#x0D; Statistical analysis of the obtained results was carried out using the standard Microsoft Excel 2019 and GraphPad Prism Software 10.1.0 software packages. (US, 2023).&#x0D; Results. The study has revealed the greatest microbial pollution of atmospheric air was found in Pavlenkivskyi Park (Kyiv District, Poltava City). The air quality index of atmospheric air in Corpusnyi Park turned out to be 4 times lower, compared to the air index of the Kyiv district. During the cultivation of atmospheric air samples taken in the Voiniv-Afghantsiv park (Shevchenkivskyi district of the city), the TCM was determined to be 8.2 times lower than that of the Pavlenkivskyi park. Interestingly, the "Peremoha" park (Shevchenkivskyi district) exhibited the lowest levels of microbial contamination. Overall, the Podilskyi district demonstrated favorable air quality indicators, surpassed only by the "Peremoha" park. However, it's important to note the presence of hemolytic streptococci in this district, which poses a potential health risk.&#x0D; Conclusion. The highest level of microbial air pollution has been found in the Kyiv district of Poltava, the lowest level is within the boundaries of the Shevchenkivskyi district on the territory of the "Peremoha" park. Microbiological air quality in Poltava's park areas exhibits an inverse relationship with proximity to the city's central roads.

Molecular Point-of-Care Testing in the Emergency Department for Group A Streptococcus Pharyngitis : A Randomized Trial.

To compare clinical and health systems outcomes of rapid molecular testing versus throat culture recovery for the management of group A Streptococcus (GAS) pharyngitis in a pediatric emergency department (PED). We conducted a single-center randomized trial of children (3-17 years) presenting to a PED with suspected GAS pharyngitis. A single dual-headed throat swab was collected, and participants were randomized to 1 of 2 parallel treatment groups with 1:1 allocation: point-of-care (POC) nucleic acid amplification testing or standard throat culture. The primary outcomes were time to throat pain +/- fever resolution. Secondary outcomes included absenteeism, length of stay, return visits to care, and antibiotic prescriptions and utilization. A total of 227 children were randomly assigned to culture (n = 115) or POC (n = 112) testing. Antibiotics were initiated earlier in the POC group by approximately 1 day (95% confidence interval, -0.40 to -1.58). No associated difference in time to throat pain or fever resolution was observed between groups. There was a decrease in the proportion of prescribed antibiotics in the POC group (0.35) compared with the culture group (0.79; P < 0.001). Otherwise, no significant differences in secondary outcomes were observed. Establishing a POC nucleic acid amplification testing program for GAS in a PED facilitates earlier treatment and fewer antibiotic prescriptions. Although this did not translate to improved clinical and health systems outcomes in our study, it may serve as an important tool amid evolving pediatric febrile illnesses and growing antimicrobial resistance patterns.

Appropriateness of Use of Streptococcal Pharyngitis Testing and Associated Antibiotic Prescribing in the Urgent Care Setting.

The primary objective was to evaluate Group A streptococcal (GAS) tests performed with a Modified Centor Criteria (MCC) Score < 3 at Urgent Care Clinics (UCC). Secondary objectives included evaluating the MCC sensitivity and specificity, antibiotics prescribed with an MCC score < 3, and association between palatal petechiae and GAS pharyngitis infections. This was a retrospective review from July 1, 2018, to June 30, 2019, of Rapid Antigen Detection Tests (RADTs) on patients with ICD codes associated with pharyngitis. Fifteen hundred patient charts were reviewed. The majority of MCC scores were < 3 at 60.0% (878/1464). Sensitivity of GAS testing (RADT/culture) slightly increased for MCC scores ≥ 3 and was better than the specificity of those scores. In comparison, MCC scores < 3, showed better specificity compared to sensitivity. Over 50% of RADTs performed were inappropriate per clinical guidelines. MCC score < 3 had higher rates of negative test results.

Group A Streptococcus pharyngitis in Children: New Perspectives on Rapid Diagnostic Testing and Antimicrobial Stewardship.

The most common cause of bacterial pharyngitis is Group A Streptococcus (GAS). Accurate diagnosis of GAS pharyngitis is crucial to identify children who would benefit from antibiotic treatment. Rapid diagnosis has the potential to reduce antibiotic overuse. Current national guidelines differ in their recommendations for GAS testing. While rapid antigen detection tests (RADTs) are widely used, their sensitivity is considered too low for stand-alone testing by several expert bodies. Newer molecular tests using nucleic acid amplification show higher accuracy and fast results, but their cost, complexity, and very high sensitivity may limit widespread adoption. This review provides up-to-date evidence regarding rapid diagnostic testing and antimicrobial stewardship in children with sore throat. We discuss discrepancies across GAS testing guidelines at the international level, patient selection for testing for GAS, rapid test accuracy, and the potential role of rapid GAS tests to promote antibiotic stewardship, with emphasis on emerging rapid molecular tests.

Group A streptococcal collagen-like protein 1 restricts tumor growth in murine pancreatic adenocarcinoma and inhibits cancer-promoting neutrophil extracellular traps.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer associated with an immunosuppressive environment. Neutrophil extracellular traps (NETs) were initially described in the context of infection but have more recently been implicated in contributing to the tolerogenic immune response in PDAC. Thus, NETs are an attractive target for new therapeutic strategies. Group A Streptococcus (GAS) has developed defensive strategies to inhibit NETs. In the present work, we propose utilizing intra-tumoral GAS injection to stimulate anti-tumor activity by inhibiting cancer-promoting NETs. Mice harboring Panc02 or KPC subcutaneous tumors injected with three different M-type GAS strains. Tumors and spleens were harvested at the endpoint of the experiments to assess bacterial colonization and systemic spread, while sera were analyzed for humoral responses toward the streptococcal antigens, especially the M1 and Scl1 proteins. Role of the streptococcal collagen-like protein 1 (Scl1) in anti-PDAC activity was assessed in vivo after intratumoral injection with M1 GAS wild-type, an isogenic mutant strain devoid of Scl1, or a complemented mutant strain with restored scl1 expression. In addition, recombinant Scl1 proteins were tested for NET inhibition using in vitro and ex vivo assays assessing NET production and myeloperoxidase activity. Injection of three different M-type GAS strains reduced subcutaneous pancreatic tumor volume compared to control in two different murine PDAC models. Limitation of tumor growth was dependent on Scl1, as isogenic mutant strain devoid of Scl1 did not reduce tumor size. We further show that Scl1 plays a role in localizing GAS to the tumor site, thereby limiting the systemic spread of bacteria and off-target effects. While mice did elicit a humoral immune response to GAS antigens, tested sera were weakly immunogenic toward Scl1 antigen following intra-tumoral treatment with Scl1-expressing GAS. M1 GAS inhibited NET formation when co-cultured with neutrophils while Scl1-devoid mutant strain did not. Recombinant Scl1 protein inhibited NETs ex vivo in a dose-dependent manner by suppressing myeloperoxidase activity. Altogether, we demonstrate that intra-tumoral GAS injections reduce PDAC growth, which is facilitated by Scl1, in part through inhibition of cancer promoting NETs. This work offers a novel strategy by which NETs can be targeted through Scl1 protein and potentiates its use as a cancer therapeutic.

Recent Scientific Advancements towards a Vaccine against Group A Streptococcus.

Group A Streptococcus (GAS), or Streptococcus pyogenes, is a gram-positive bacterium that extensively colonises within the human host. GAS is responsible for causing a range of human infections, such as pharyngitis, impetigo, scarlet fever, septicemia, and necrotising fasciitis. GAS pathogens have the potential to elicit fatal autoimmune sequelae diseases (including rheumatic fever and rheumatic heart diseases) due to recurrent GAS infections, leading to high morbidity and mortality of young children and the elderly worldwide. Antibiotic drugs are the primary method of controlling and treating the early stages of GAS infection; however, the recent identification of clinical GAS isolates with reduced sensitivity to penicillin-adjunctive antibiotics and increasing macrolide resistance is an increasing threat. Vaccination is credited as the most successful medical intervention against infectious diseases since it was discovered by Edward Jenner in 1796. Immunisation with an inactive/live-attenuated whole pathogen or selective pathogen-derived antigens induces a potent adaptive immunity and protection against infectious diseases. Although no GAS vaccines have been approved for the market following more than 100 years of GAS vaccine development, the understanding of GAS pathogenesis and transmission has significantly increased, providing detailed insight into the primary pathogenic proteins, and enhancing GAS vaccine design. This review highlights recent advances in GAS vaccine development, providing detailed data from preclinical and clinical studies across the globe for potential GAS vaccine candidates. Furthermore, the challenges and future perspectives on the development of GAS vaccines are also described.

Clinical, microbiological, and molecular characterization of pediatric invasive infections by Streptococcus pyogenes in Spain in a context of global outbreak.

Group A Streptococcus (GAS) is a common bacterial pathogen in the pediatric population. In the last months of 2022, an unusual increase in GAS infections was detected in various countries. Certain strains were overrepresented, although the cause of this raise is not clear. In Spain, a significant increase in mild and severe cases was also observed; this study evaluates the clinical characteristics and the strains involved in both scenarios. Our study showed that the increase in incidence did not correlate with an increase in resistance or with an emm types shift. However, there seemed to be a rise in severity, partly related to a greater rate of pneumonia cases. These findings suggest a general increase in iGAS that highlights the need for surveillance. The introduction of whole genome sequencing in the diagnosis and surveillance of iGAS may improve the understanding of antibiotic resistance, virulence, and clones, facilitating its control and personalized treatment.

Preadmission course and management of severe pediatric group A streptococcal infections during the 2022-2023 outbreak: a single-center experience.

The massive increase of infections with Group A Streptococcus (GAS) in 2022-2023 coincided in Switzerland with a change of the recommendations for the management of GAS pharyngitis. Therefore, the objective of the present study was to investigate whether the clinical manifestations and management before hospitalization for GAS infection differed in 2022-2023 compared with 2013-2022. Retrospective study of GAS infections requiring hospitalization in patients below 16years. Preadmission illness (modified McIsaac score), oral antibiotic use, and outcome in 2022-2023 were compared with 2013-2022. Time series were compared with surveillance data for respiratory viruses. In 2022-2023, the median modified McIsaac score was lower (2 [IQR 2-3] vs. 3 [IQR 2-4], p = < 0.0001) and the duration of preadmission illness was longer (4days [3-7] vs. 3 [2-6], p = 0.004) than in 2013-2022. In both periods, withholding of preadmission oral antibiotics despite a modified McIsaac score ≥ 3 (12% vs. 18%, n.s.) or ≥ 4 (2.4% vs. 10.0%, p = 0.027) was rare. Respiratory disease, skeletal/muscle infection, and invasive GAS disease were significantly more frequent in 2022-2023, but there were no differences in clinical outcome. The time course of GAS cases in 2022-2023 coincided with the activity of influenza A/B. We found no evidence supporting the hypothesis that the 2022-2023 GAS outbreak was associated with a change in preadmission management possibly induced by the new recommendation for GAS pharyngitis. However, clinical manifestations before admission and comparative examination of time-series strongly suggest that viral co-circulation played an important role in this outbreak.

Conserved molecular chaperone PrsA stimulates protective immunity against group A Streptococcus

Group A Streptococcus (GAS) is a significant human pathogen that poses a global health concern. However, the development of a GAS vaccine has been challenging due to the multitude of diverse M-types and the risk of triggering cross-reactive immune responses. Our previous research has identified a critical role of PrsA1 and PrsA2, surface post-translational molecular chaperone proteins, in maintaining GAS proteome homeostasis and virulence traits. In this study, we aimed to further explore the potential of PrsA1 and PrsA2 as vaccine candidates for preventing GAS infection. We found that PrsA1 and PrsA2 are highly conserved among GAS isolates, demonstrating minimal amino acid variation. Antibodies specifically targeting PrsA1/A2 showed no cross-reactivity with human heart proteins and effectively enhanced neutrophil opsonophagocytic killing of various GAS serotypes. Additionally, passive transfer of PrsA1/A2-specific antibodies conferred protective immunity in infected mice. Compared to alum, immunization with CFA-adjuvanted PrsA1/A2 induced higher levels of Th1-associated IgG isotypes and complement activation and provided approximately 70% protection against invasive GAS challenge. These findings highlight the potential of PrsA1 and PrsA2 as universal vaccine candidates for the development of an effective GAS vaccine.

Microscopic identification of foodborne bacterial pathogens based on deep learning method

Accurate and rapid detection of foodborne bacterial pathogens is critical for food quality control. Nowadays, tracking morphological bacterial properties using microscope is still a priority at the grass-roots food supervision department due to its simplicity and low cost. However, the method requires highly professional personnel and there are certain misjudgments in the process of analysis. Automatically recognizing foodborne pathogen using deep learning algorithm to replace manual microscopy will not only reduce expert cost, artificial misjudgment, and operation time in detection, but also provide more objective and accurate identification. Here, we firstly constructed a high-quality and large-scale dataset of foodborne pathogenic bacteria, allowing the deep learning-based model to be efficiently trained and achieve accurate identification. The deep convolutional neural network-based model is capable of identifying six common foodborne pathogens, including Escherichia coli (O157:H7), Vibrio parahaemolyticus, Staphylococcus aureus, Bacillus cereus, Salmonella typhi, and Streptococcus hemolyticus, with accuracy rates of 90%–100%. This method can assist or replace the manual microscopic inspection step in traditional detection methods, and is promising to break through the traditional approach that heavily relies on manual judgment, greatly reduce the cost of experts and human errors, and provide rapid, accurate, and powerful discriminatory results in large quantities for detection.