The Innate Biologies of Adaptive Antigen Receptors.

Nonclonal innate immune responses mediated by germ line-encoded receptors, such as Toll-like receptors or natural killer receptors, are commonly contrasted with diverse, clonotypic adaptive responses of lymphocyte antigen receptors generated by somatic recombination. However, the Variable (V) regions of antigen receptors include germ line-encoded motifs unaltered by somatic recombination, and theoretically available to mediate nonclonal, innate responses, that are independent of or largely override clonotypic responses. Recent evidence demonstrates that such responses exist, underpinning the associations of particular γδ T cell receptors (TCRs) with specific anatomical sites. Thus, TCRγδ can make innate and adaptive responses with distinct functional outcomes. Given that αß T cells and B cells can also make nonclonal responses, we consider that innate responses of antigen receptor V-regions may be more widespread, for example, inducing states of preparedness from which adaptive clones are better selected. We likewise consider that potent, nonclonal T cell responses to microbial superantigens may reflect subversion of physiologic innate responses of TCRα/ß chains.

Obsessive-Compulsive Behavior Isn't Necessarily a Bad Thing.

It is difficult to believe that in about 1960 practically nothing was known about the thymus and some of its products, T cells bearing αß receptors for antigen. Thus I was lucky to join the field of T cell biology almost at its beginning, when knowledge about the cells was just getting off the ground and there was so much to discover. This article describes findings about these cells made by others and myself that led us all from ignorance, via complete confusion, to our current state of knowledge. I believe I was fortunate to practice science in very supportive institutions and with very collaborative colleagues in two countries that both encourage independent research by independent scientists, while simultaneously ignoring or somehow being able to avoid some of the difficulties of being a woman in what was, at the time, a male-dominated profession.

Virulence attributes of successful methicillin-resistant Staphylococcus aureus lineages.

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of severe and often fatal infections. MRSA epidemics have occurred in waves, whereby a previously successful lineage has been replaced by a more fit and better adapted lineage. Selection pressures in both hospital and community settings are not uniform across the globe, which has resulted in geographically distinct epidemiology. This review focuses on the mechanisms that trigger the establishment and maintenance of current, dominant MRSA lineages across the globe. While the important role of antibiotic resistance will be mentioned throughout, factors which influence the capacity of S. aureus to colonize and cause disease within a host will be the primary focus of this review. We show that while MRSA possesses a diverse arsenal of toxins including alpha-toxin, the success of a lineage involves more than just producing toxins that damage the host. Success is often attributed to the acquisition or loss of genetic elements involved in colonization and niche adaptation such as the arginine catabolic mobile element, as well as the activity of regulatory systems, and shift metabolism accordingly (e.g., the accessory genome regulator, agr). Understanding exactly how specific MRSA clones cause prolonged epidemics may reveal targets for therapies, whereby both core (e.g., the alpha toxin) and acquired virulence factors (e.g., the Panton-Valentine leukocidin) may be nullified using anti-virulence strategies.

Divergent effects of emm types 1 and 12 on invasive group A streptococcal infections-results of a retrospective cohort study, Germany 2023.

As a potential side effect of the severe acute respiratory syndrome coronavirus type 2 pandemic, invasive group A Streptococcus (iGAS) infections in Europe have increased dramatically in both children and adults in the end of 2022. This epidemiological and molecular study describes the distributions of streptococcal genes encoding the M antigen (emm types) and superantigens in patients with invasive and non-invasive GAS infections. From December 2022 to December 2023, a total of 163 GAS isolates were collected from sterile and non-sterile sites of patients at five hospitals in Germany including two tertiary care centers. Genes encoding M protein and superantigens were determined following the guidelines of CDC Streptococcus laboratory. Patients' characteristics were reviewed retrospectively. Correlations of clinical factors, emm types, and superantigens with rates of invasive infections were analyzed. Of the 163 included GAS cases, 112 (69%) were considered as invasive. In total, 33 different emm types were observed, of which emm1.0 (n = 49; 30%), emm89.0 (n = 15; 9%), and emm12.0 (n = 14; 9%) were most prevalent. In total, 70% of emm1.0 isolates belonged to M1UK lineage. No difference in invasive infections was observed for the M1UK lineage compared with other emm1.0 isolates. However, the emm1.0 type, presence of speA1-3, speG, or speJ, as well as adulthood were significantly associated with invasive infections. In contrast, emm12.0 isolates were significantly less associated with invasive infections. Multivariable analysis confirmed a significant influence of speJ and adulthood on iGAS infections. This study underlines the importance of continuous monitoring of genomic trends and identification of emerging GAS variants. This may aid in delineating pathogenicity factors of Streptococcus pyogenes that propel invasive infections.

Tumor-targeted superantigens produce curative tumor immunity with induction of memory and demonstrated antigen spreading.

BACKGROUND: Despite remarkable progress, the immunotherapies currently used in the clinic, such as immune checkpoint blockade (ICB) therapy, still have limited efficacy against many types of solid tumors. One major barrier to effective treatment is the lack of a durable long-term response. Tumor-targeted superantigen (TTS) therapy may overcome this barrier to enhance therapeutic efficacy. TTS proteins, such as the clinical-stage molecule naptumomab estafenatox (NAP), increase tumor recognition and killing by both coating tumor cells with bacterial-derived superantigens (SAgs) and selectively expanding T-cell lineages that can recognize them. The present study investigated the efficacy and mechanism of action of repeated TTS (C215Fab-SEA) treatments leading to a long-term antitumor immune response as monotherapy or in combination with PD-1/PD-L1 inhibitors in murine tumor models. METHODS: We used syngeneic murine tumor models expressing the human EpCAM target (C215 antigen) to assess the efficacy and mechanism of action of repeated treatment with TTS C215Fab-SEA alone or with anti-PD-1/PD-L1 monoclonal antibodies. Tumor draining lymph nodes (TDLNs) and tumor tissues were processed and analyzed by immunophenotyping and immunohistochemistry. Isolated RNA from tumors was used to analyze gene expression and the TCR repertoire. Tumor rechallenge and T-cell transfer studies were conducted to test the long-term antitumor memory response. RESULTS: TTS therapy inhibited tumor growth and achieved complete tumor rejection, leading to a T-cell-dependent long-term memory response against the tumor. The antitumor effect was derived from inflammatory responses converting the immunosuppressive TME into a proinflammatory state with an increase in T-cell infiltration, activation and high T-cell diversity. The combination of TTS with ICB therapy was significantly more effective than the monotherapies and resulted in higher tumor-free rates. CONCLUSIONS: These new results indicate that TTSs not only can turn a "cold" tumor into a "hot" tumor but also can enable epitope spreading and memory response, which makes TTSs ideal candidates for combination with ICB agents and other anticancer agents.

Photoactivated Gallium Porphyrin Reduces Staphylococcus aureus Colonization on the Skin and Suppresses Its Ability to Produce Enterotoxin C and TSST-1.

Staphylococcus aureus is a key pathogen in atopic dermatitis (AD) pathogenicity. Over half of AD patients are carriers of S. aureus. Clinical isolates derived from AD patients produce various staphylococcal enterotoxins, such as staphylococcal enterotoxin C or toxic shock syndrome toxin. The production of these virulence factors is correlated with more severe AD. In this study, we propose cationic heme-mimetic gallium porphyrin (Ga3+CHP), a novel gallium metalloporphyrin, as an anti-staphylococcal agent that functions through dual mechanisms: a light-dependent mechanism (antimicrobial photodynamic inactivation, aPDI) and a light-independent mechanism (suppressing iron metabolism). Ga3+CHP has two additive quaternary ammonium groups that increase its water solubility. Furthermore, Ga3+CHP is an efficient generator of singlet oxygen and can be recognized by heme-target systems such as Isd, which improves the intracellular accumulation of this compound. Ga3+CHP activated with green light effectively reduced the survival of clinical S. aureus isolates derived from AD patients (>5 log10 CFU/mL) and affected their enterotoxin gene expression. Additionally, there was a decrease in the biological functionality of studied toxins regarding their superantigenicity. In aPDI conditions, there was no pronounced toxicity in HaCaT keratinocytes with both normal and suppressed filaggrin gene expression, which occurs in ∼50% of AD patients. Additionally, no mutagenic activity was observed. Green light-activated gallium metalloporphyrins may be a promising chemotherapeutic to reduce S. aureus colonization on the skin of AD patients.

Autoimmunity: A New Focus on Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) has long been considered a benign, chronic inflammatory, and hyperplastic disease. Recent studies have shown that autoimmune-related mechanisms are involved in the pathology of nasal polyps. Activated plasma cells, eosinophils, basophils, innate type 2 lymphocytes, mast cells, and proinflammatory cytokine in polyp tissue indicate the mobilization of innate and adaptive immune pathways during polyp formation. The discovery of a series of autoantibodies further supports the autoimmune nature of nasal polyps. Local homeostasis dysregulation, infection, and chronic inflammation may trigger autoimmunity through several mechanisms, including autoantigens overproduction, microbial translocation, molecular mimicry, superantigens, activation or inhibition of receptors, bystander activation, dysregulation of Toll-Like Receptors (TLRs), epitope spreading, autoantigens complementarity. In this paper, we elaborated on the microbiome-mediated mechanism, abnormal host immunity, and genetic changes to update the role of autoimmunity in the pathogenesis of chronic rhinosinusitis with nasal polyps.

Molecular Genetic Characterization of Streptococcus pyogenes Strains Isolated from Patients with Various Manifestations of Streptococcal Infection.

In 82 clinical strains of Streptococcus pyogenes (group A streptococci) isolated from patients with various manifestations of streptococcal infection, emm-typing revealed 27 emm-types (n=77) with a predominance of emm-89 (n=15; 18%), emm-75 (n=9; 11%), and emm-1 (n=6; 7%); types emm-3, emm-12, and emm-58 (n=4; 5% each) were found with almost equal frequency; other types were less common. The superantigen genes speC, speG, speH, speI, speJ, speK, speL, speM, smeZ, and SSA were identified in S. pyogenes strains using multiprimer PCR; the genes of the superantigen SpeA and cysteine proteinase SpeB were detected using real-time PCR. All the studied S. pyogenes strains contained superantigen genes, and 98% of the strains had several (from 2 to 7) genes. The number of variants of these sets reached 37; 2% of the strains contained only one superantigen gene. The distribution frequencies of superantigen genes in the studied strains were: speA - 43%; speC - 38%; speG - 93%; speH - 13%; speI - 6%; speJ - 24%; speK - 13%; speL and speM - 11% each; smeZ - 98%; SSA - 15%. All studied S. pyogenes strains contained the speB gene. Our studies have demonstrated that the sets of superantigen genes of group A streptococci are characterized by pronounced diversity to some extent associated with emm-type.

Immunological characteristics of severe acute hepatitis of unknown origin in a child post SARS-CoV-2 infection.

Recent studies have reported that pediatric acute liver failure of unknown origin is immune-mediated, with CD8+ T cells playing a key role. Moreover, investigation of superantigen-mediated T-cell activation by the SARS-CoV-2 spike protein in pediatric severe acute hepatitis is needed in the context of the proposed mechanism of multisystem inflammatory syndrome in children (MIS-C). We investigated the immunological characteristics of a Japanese pediatric patient with severe acute hepatitis post SARS-CoV-2 infection. The patient demonstrated autoimmune hepatitis-like liver histology with CD8+ lymphocyte-predominant infiltration. There was Th1-type immune skewing, including remarkable peripheral CD8+ T-cell activation and a skewed T cell receptor repertoire. We also found elevated plasma levels of the anti-SARS-CoV-2 spike-specific IgG antibody, and the titer peaked after treatment, as seen with MIS-C. These findings support that immunological activation involving SARS-CoV-2 spike protein plays a crucial role in a pediatric patient with acute severe hepatitis post SARS-CoV-2 infection.

MAIT Cells Are Major Contributors to the Cytokine Response in Group A Streptococcal Toxic Shock Syndrome.

Streptococcal toxic shock syndrome (STSS) is a rapidly progressing, life-threatening, systemic reaction to invasive infection caused by group A streptococci (GAS). GAS superantigens are key mediators of STSS through their potent activation of T cells leading to a cytokine storm and consequently vascular leakage, shock, and multiorgan failure. Mucosal-associated invariant T (MAIT) cells recognize MR1-presented antigens derived from microbial riboflavin biosynthesis and mount protective innate-like immune responses against the microbes producing such metabolites. GAS lack de novo riboflavin synthesis, and the role of MAIT cells in STSS has therefore so far been overlooked. Here we have conducted a comprehensive analysis of human MAIT cell responses to GAS, aiming to understand the contribution of MAIT cells to the pathogenesis of STSS. We show that MAIT cells are strongly activated and represent the major T cell source of IFNγ and TNF in the early stages of response to GAS. MAIT cell activation is biphasic with a rapid TCR Vß2-specific, TNF-dominated response to superantigens and a later IL-12- and IL-18-dependent, IFNγ-dominated response to both bacterial cells and secreted factors. Depletion of MAIT cells from PBMC resulted in decreased total production of IFNγ, IL-1ß, IL-2, and TNFß. Peripheral blood MAIT cells in patients with STSS expressed elevated levels of the activation markers CD69, CD25, CD38, and HLA-DR during the acute compared with the convalescent phase. Our data demonstrate that MAIT cells are major contributors to the early cytokine response to GAS, and are therefore likely to contribute to the pathological cytokine storm underlying STSS.

Distribution of emm, superantigen and other virulence genotypes and detection of phylogenetic relationships in group A streptococcal isolates.

Group A streptococci are important pathogens with various virulence factors, such as M protein, superantigens, hemolysins, deoxyribonuclease, and proteases. The aims of this study are to investigate the detection of emm genotypes and other virulence genes, such as SAgs, DNase, protease, antibiotic resistance, and phylogenetic relationships in GAS strains isolated from clinical samples.Test strains were obtained from Çukurova University Balcali Hospital and regional hospitals in Adana province. The M proteins were detected by sequence analysis of emm genes. SAgs and other virulence gene profiles were determined using the Multiplex-PCR method. The antibiotic susceptibility of the isolates was performed by the disc diffusion method and evaluated according to CLSI criteria. The PFGE method was used to determine the clonal relationship between the strains.The emm gene was positive in 86 isolates. The most common emm genotypes were emm28 (22%), emm1 (18.6%), emm12 (13.9%), and emm3 (11.6%). Also, the most common virulence genes were speG (58.1%), speC (56.9%), sdaB (53.4%), and mac (53.4%). The rates of resistance to erythromycin, clindamycin, levofloxacin, ciprofloxacin and telithromycin were 19.8%, 16.3%, 4.7%, 3.5%, and 3.5%, respectively.As a result, additional regional studies on the detection and prevalence of GAS virulence factors in Turkey are required. We believe that this study will provide valuable information for epidemiological studies on emm sequences, Sags, and other virulence factors of Streptococcus pyogenes in Turkey.

SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19.

The review aims to consolidate research findings on the molecular mechanisms and virulence and pathogenicity characteristics of coronavirus disease (COVID-19) causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their relevance to four typical stages in the development of acute viral infection. These four stages are invasion; primary blockade of antiviral innate immunity; engagement of the virus's protection mechanisms against the factors of adaptive immunity; and acute, long-term complications of COVID-19. The invasion stage entails the recognition of the spike protein (S) of SARS-CoV-2 target cell receptors, namely, the main receptor (angiotensin-converting enzyme 2, ACE2), its coreceptors, and potential alternative receptors. The presence of a diverse repertoire of receptors allows SARS-CoV-2 to infect various types of cells, including those not expressing ACE2. During the second stage, the majority of the polyfunctional structural, non-structural, and extra proteins SARS-CoV-2 synthesizes in infected cells are involved in the primary blockage of antiviral innate immunity. A high degree of redundancy and systemic action characterizing these pathogenic factors allows SARS-CoV-2 to overcome antiviral mechanisms at the initial stages of invasion. The third stage includes passive and active protection of the virus from factors of adaptive immunity, overcoming of the barrier function at the focus of inflammation, and generalization of SARS-CoV-2 in the body. The fourth stage is associated with the deployment of variants of acute and long-term complications of COVID-19. SARS-CoV-2's ability to induce autoimmune and autoinflammatory pathways of tissue invasion and development of both immunosuppressive and hyperergic mechanisms of systemic inflammation is critical at this stage of infection.

Comparison of superantigens and attachment factors genes of Staphylococcus aureus in clinical isolates and nasal colonizers in the same patients.

BACKGROUND: Staphylococcus aureus (S. aureus) is a bacterial pathogen can cause a wide range of nosocomial infections. Nasal colonization by S.aureus plays important role both in the epidemiology and pathogenesis of infection. OBJECTIVES: The purpose of this study was to investigate the association of clinical isolates and nasal colonizers of S. aureus in the same patients by molecular methods, and their antibiotic susceptibility pattern. METHODS: A total of 181 S. aureus isolates were collected from 100 patients admitted that including 100 clinical isolates and 81 nasal swabs from the same patients (19 cases were found as noncarriers). Superantigens and adhesion genes were identified by PCR. Molecular typing of the isolates was performed by repetitive element polymerase chain reaction (Rep-PCR). Antimicrobial susceptibility pattern of the isolates was conducted by disk diffusion. MIC of the isolates to vancomycin was determined by microbroth dilution. The ability of S. aureus isolates to form biofilm was determined by microtiter plate assay. RESULTS: The most frequent adhesion gene in both clinical isolates and nasal colonizer was clfA with 93% and 76%, respectively. Staphylococcal enterotoxin A (SEA) was the most commonly superantigen (68%) in both nasal colonizers (71.6%) and clinical isolates (65%). The highest resistance rate was to erythromycin (45.3%) with 36% and 56.8% in clinical and nasal colonizer isolates, respectively. All S. aureus isolates were susceptible to linezolid and vancomycin. Multiple drug resistance (MDR) was detected in 36% (n = 65) of the isolates. Biofilm formation was identified in 160 (88.4%) isolates with 87% and 90% in clinical isolates and nasal colonizers, respectively. Repetitive element polymerase chain reaction (Rep-PCR) typing divided 181 S. aureus isolates into six clusters. Twelve isolates from clinical isolates and nasal carriers were closely related. CONCLUSION: There is a high concordance rate between colonizing and clinical isolates of S. aureus in terms of adhesion factors and superantigen genes. It is suggested that nasal decolonization could be effective in the preventing of S. aureus infections.

Antigen-Antibody Complexes.

In vertebrates, immunoglobulins (Igs), commonly known as antibodies, play an integral role in the armamentarium of immune defense against various pathogens. After an antigenic challenge, antibodies are secreted by differentiated B cells called plasma cells. Antibodies have two predominant roles that involve specific binding to antigens to launch an immune response, along with activation of other components of the immune system to fight pathogens. The ability of immunoglobulins to fight against innumerable and diverse pathogens lies in their intrinsic ability to discriminate between different antigens. Due to this specificity and high affinity for their antigens, antibodies have been a valuable and indispensable tool in research, diagnostics and therapy. Although seemingly a simple maneuver, the association between an antibody and its antigen, to make an antigen-antibody complex, is comprised of myriads of non-covalent interactions. Amino acid residues on the antigen binding site, the epitope, and on the antibody binding site, the paratope, intimately contribute to the energetics needed for the antigen-antibody complex stability. Structural biology methods to study antigen-antibody complexes are extremely valuable tools to visualize antigen-antibody interactions in detail; this helps to elucidate the basis of molecular recognition between an antibody and its specific antigen. The main scope of this chapter is to discuss the structure and function of different classes of antibodies and the various aspects of antigen-antibody interactions including antigen-antibody interfaces-with a special focus on paratopes, complementarity determining regions (CDRs) and other non-CDR residues important for antigen binding and recognition. Herein, we also discuss methods used to study antigen-antibody complexes, antigen recognition by antibodies, types of antigens in complexes, and how antigen-antibody complexes play a role in modern day medicine and human health. Understanding the molecular basis of antigen binding and recognition by antibodies helps to facilitate the production of better and more potent antibodies for immunotherapy, vaccines and various other applications.

Staphylococcus aureus internalization in mast cells in nasal polyps: Characterization of interactions and potential mechanisms.

BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps is a common chronic condition. The exact cause of nasal polyps remains unknown. Recently, we made the novel observation of intracellular localization of Staphylococcus aureus within mast cells in nasal polyps. OBJECTIVE: This follow-up study aimed to further characterize interactions between S aureus and mast cells in this setting and elucidate potential internalization mechanisms with particular emphasis on the role of staphylococcal enterotoxin B (SEB). METHODS: A prospective study was performed using an explant tissue model with ex vivo inferior turbinate mucosa obtained from patients with chronic rhinosinusitis with nasal polyps (n = 7) and patients without CRS (n = 5). Immunohistochemistry was used to characterize S aureus uptake into mast cells and investigate the effects of SEB on this process. An in vitro cell-culture model was used to investigate mast cell-S aureus interactions by using a combination of fluorescent in situ hybridization, confocal laser scanning microscopy, scanning electron microscopy, transmission electron microscopy, and proliferation assays. RESULTS: S aureus was captured by extracellular traps and entered mast cells through phagocytosis. Proliferating intracellular S aureus led to the expansion and eventual rupture of mast cells, resulting in release of viable S aureus into the extracellular space. The presence of SEB appeared to promote internalization of S aureus into mast cells. CONCLUSION: This study provides new insights into the interactions between S aureus and mast cells, including the internalization process, and demonstrates a prominent role for SEB in promoting uptake of the bacteria into these cells.

Staphylococcus aureus Isolated from Skin from Atopic-Dermatitis Patients Produces Staphylococcal Enterotoxin Y, Which Predominantly Induces T-Cell Receptor Vα-Specific Expansion of T Cells.

While investigating the virulence traits of Staphylococcus aureus adhering to the skin of atopic-dermatitis (AD) patients, we identified a novel open reading frame (ORF) with structural similarity to a superantigen from genome sequence data of an isolate from AD skin. Concurrently, the same ORF was identified in a bovine isolate of S. aureus and designated SElY (H. K. Ono, Y. Sato'o, K. Narita, I. Naito, et al., Appl Environ Microbiol 81:7034-7040, 2015, https://doi.org/10.1128/AEM.01873-15). Recombinant SElYbov had superantigen activity in human peripheral blood mononuclear cells. It further demonstrated emetic activity in a primate animal model, and it was proposed that SElY be renamed SEY (H. K. Ono, S. Hirose, K. Narita, M. Sugiyama, et al., PLoS Pathog 15:e1007803, 2019, https://doi.org/10.1371/journal.ppat.1007803). Here, we investigated the prevalence of the sey gene in 270 human clinical isolates of various origins in Japan. Forty-two strains were positive for the sey gene, and the positive isolates were from patients with the skin diseases atopic dermatitis and impetigo/staphylococcal scalded skin syndrome (SSSS), with a detection rate of ∼17 to 22%. There were three variants of SEY (SEY1, SEY2, and SEY3), and isolates producing SEY variants formed three distinct clusters corresponding to clonal complexes (CCs) 121, 59, and 20, respectively. Most sey+ isolates produced SEY in broth culture. Unlike SEYbov, the three recombinant SEY variants exhibited stability against heat treatment. SEY predominantly activated human T cells with a particular T-cell receptor (TCR) Vα profile, a unique observation since most staphylococcal enterotoxins exert their superantigenic activities through activating T cells with specific TCR Vß profiles. SEY may act to induce localized inflammation via skin-resident T-cell activation, facilitating the pathogenesis of S. aureus infection in disrupted epithelial barriers.

Correlation Between Immunoglobulin Dose Administered and Plasma Neutralization of Streptococcal Superantigens in Patients With Necrotizing Soft Tissue Infections.

Analyses of plasma collected pre- and postadministration of intravenous immunoglobulin (IVIG) from patients with group A Streptococcus necrotizing soft tissue infections demonstrated a negative correlation between IVIG dose and toxin-triggered T-cell proliferation (r = -.67, P < .0001). One 25-g IVIG dose was sufficient to yield plasma-neutralizing activity against streptococcal superantigens. Clinical Trials Registration. NCT01790698 and NCT02111161.

Epidemiological analysis of Group A Streptococcus infections in a hospital in Beijing, China.

Our study aimed to investigate the epidemiological and molecular characteristics of isolates collected from Group A Streptococcus (GAS) infections in children in Beijing China during the year 2019. Emm typing, superantigens, and erythromycin resistance genotypes were determined by PCR. Antimicrobial susceptibility testing was performed as recommended by Clinical Laboratory Standards Institute (CLSI). A total of 271 GAS isolates were collected. Thirteen different emm types, including 31 subtypes, were identified. The most prevalent emm types were emm12 (52.77%), emm1 (36.9%), emm3.1 (2.95%), and emm75.0 (2.95%). Two variant subtypes, STC36.0 and STG840.2, were identified. There was no difference in the portion of emm12 and emm1 isolates in scarlet fever, impetigo, and psoriasis. The majority of superantigens detected were smeZ (94.46%), speC (91.14%), and ssa (74.91%), followed by speH (56.46%), speI (45.76%), speJ (36.9%), and speA (34.32%). More scarlet fever isolates harbored speA (35.6%) and speJ (38.4%), more psoriasis isolates harbored speI (57.9%), and more impetigo isolates harbored ssa (89.7%). Isolates were universally susceptible to penicillin and resistant to erythromycin (94.83%). Moreover, 89.67% erythromycin resistance isolates harbored the ermB gene. The erythromycin resistance rate of the isolates from the three diseases was different. Scarlet fever is the common streptococcal infectious disease in dermatology. Emm12 and emm1 were the most prevalent emm types. The most prevalent superantigens detected were smeZ, spec, and ssa. There is association between diversity of superantigens and disease manifestation. Hence, continuous surveillance of GAS molecular epidemiological characterizations in different diseases is needed.

Molecular epidemiology and antimicrobial resistance of group a streptococcus recovered from patients in Beijing, China.

BACKGROUND: Group A streptococcus (GAS) is an important human pathogen responsible for a broad range of infections. Epidemiological surveillance has been crucial to detect changes in the geographical and temporal variation of the disease pattern. The objective of this study was to investigate the molecular epidemiological characteristics and antimicrobial resistance of GAS isolates from patients in Children's Hospital in Beijing. METHODS: From 2016 to 2017, pharyngeal swab samples were collected from the outpatients in Children's Hospital, Capital Institute of Pediatrics, who were diagnosed with scarlet fever. Antimicrobial susceptibility test was performed according to the distribution of conventional antibiotics and Clinical and Laboratory Standards Institute (CLSI) recommendations. The distribution of the macrolide-resistance genes (ermB, ermA, mefA), emm (M protein-coding gene) typing, and superantigens (SAg) gene profiling were examined by polymerase chain reaction (PCR). RESULTS: A total of 297 GAS isolates were collected. The susceptibility of the isolates to penicillin, ceftriaxone, and levofloxacin was 100%. The resistance rate to erythromycin and clindamycin was 98.3 and 96.6%, respectively. The dominant emm types were emm12 (65.32%), emm1 (27.61%), emm75 (2.69%), and emm89 (1.35%). Of the 297 isolates, 290 (97.64%) carried the ermB gene, and 5 (1.68%) carried the mefA gene, while none carried the ermA gene. The most common superantigen genes identified from GAS isolates were smeZ (96.97%), speC (92.59%), speG (91.58%), ssa (85.52%), speI (54.55%), speH (52.19%), and speA (34.34%). Isolates with the genotype emm1 possessed speA, speC, speG, speJ, speM, ssa, and smeZ, while emm12 possessed speC, speG, speH, speI, speM, ssa, and smeZ superantigens. CONCLUSIONS: The prevalent strain of GAS isolates in Beijing has a high resistance rate to macrolides; however, penicillin can still be the preferred antibiotic for treatment. Erythromycin resistance was predominantly mediated by ermB. The common emm types were emm12 and emm1. There was a correlation between emm and the superantigen gene. Thus, long-term monitoring and investigation of the emm types and superantigen genes of GAS prevalence are imperative.

T Cell Immunity to Bacterial Pathogens: Mechanisms of Immune Control and Bacterial Evasion.

The human body frequently encounters harmful bacterial pathogens and employs immune defense mechanisms designed to counteract such pathogenic assault. In the adaptive immune system, major histocompatibility complex (MHC)-restricted αß T cells, along with unconventional αß or γδ T cells, respond to bacterial antigens to orchestrate persisting protective immune responses and generate immunological memory. Research in the past ten years accelerated our knowledge of how T cells recognize bacterial antigens and how many bacterial species have evolved mechanisms to evade host antimicrobial immune responses. Such escape mechanisms act to corrupt the crosstalk between innate and adaptive immunity, potentially tipping the balance of host immune responses toward pathological rather than protective. This review examines the latest developments in our knowledge of how T cell immunity responds to bacterial pathogens and evaluates some of the mechanisms that pathogenic bacteria use to evade such T cell immunosurveillance, to promote virulence and survival in the host.