Molecular characterization of a novel putative pathogen, Streptococcus nakanoensis sp. nov., isolated from sputum culture.

Reports of novel species of α-hemolytic Streptococcus have increased recently. However, limited information exists regarding the pathogenicity of these species, with the exception of Streptococcus pneumoniae and Streptococcus pseudopneumoniae. In this study, a quinolone-resistant α-Streptococcus strain, MTG105, was isolated from the sputum of a patient with pneumonia. This strain was first identified as S. pneumoniae at the hospital laboratory; however, it exhibited unique genetic features upon further analysis. Digital DNA-DNA hybridization and average nucleotide identity based on BLAST values from whole-genome sequencing revealed MTG105 to be a novel species closely related to S. pseudopneumoniae. Although MTG105 carried two copies of the pneumolysin gene, similar to S. pseudopneumoniae, this isolate exhibited susceptibility to optochin under both aerobic and 5% CO2 conditions. Notably, no biochemical features could be used to definitively identify this species. In an infection assay using organotypic lung tissue models, MTG105 induced epithelial damage comparable to that of S. pneumoniae and S. pseudopneumoniae, possibly suggesting its potential as a pathogenic α-Streptococcus. The natural transformation abilities of Streptococcus species facilitate their exchange of genes within the same genus, resulting in the existence of species with increasingly more diverse genome structures. Therefore, the identification of this species highlights the importance of monitoring the emergence of novel species exhibiting virulence and/or multidrug resistance. This isolate was proposed as a novel species, designated Streptococcus nakanoensis sp. nov. The type strain was MTG 105T (= JCM 35953T = CCUG 76894T). IMPORTANCE: The genus Streptococcus encompasses a wide range of bacteria with more than 60 species. Recently, there has been a notable increase in reports of novel species of α-Streptococcus based on genomic analysis data. However, limited information exists regarding the pathogenicity of these species. In this study, a quinolone-resistant α-hemolytic Streptococcus strain, MTG105, was isolated from a patient with pneumonia. Genetic analysis revealed that this species was a novel species closely related to S. pseudopneumoniae. In an infection assay using organotypic lung tissue models, MTG105 induced epithelial damage comparable to that caused by S. pneumoniae and S. pseudopneumoniae, strongly suggesting its potential as a pathogenic α-Streptococcus. The natural transformation abilities of Streptococcus species facilitate gene exchange within the same genus, leading to the emergence of species with increasingly diverse genome structures. Therefore, the identification of this species underscores the importance of monitoring the emergence of novel species exhibiting virulence and/or multidrug resistance.

Analysis of bacteraemia caused by group C and G Streptococcus (Streptococcus dysgalactiae subsp. equisimilis) in Western Sydney over a 6-year period (2015-2020).

PURPOSE: Streptococcus dysgalactiae subsp. equisimilis (SDSE) has increasingly been recognised as a significant pathogen that causes a myriad of infections, ranging from cellulitis to invasive infections, including bacteraemia and even toxic shock syndrome. The aim of this study was to examine the epidemiology and disease manifestations of bacteraemia caused by SDSE. METHODS: We retrospectively reviewed cases of SDSE bacteraemia in adults aged ≥ 18 years admitted to four public hospitals in Western Sydney, Australia, between January 2015 and December 2020. We reviewed demographics, comorbidities, disease manifestations, management, and outcomes. RESULTS: There were 108 patients with SDSE bacteraemia over a six-year period. The median age of individuals with SDSE bacteraemia was 70 years (interquartile range, IQR, 58-85 years). Cardiovascular disease (46%), chronic skin conditions (44%) and diabetes (37%) were the most common comorbidities. Ten patients (9%) with SDSE bacteraemia had healthcare-acquired infections. Skin and skin structure infections (SSTIs) were the most common presentations (59%), while bone and joint infections (BJIs) represented 13% of the cases. Twenty patients (19%) had septic shock on presentation. Fifteen patients (14%) were prescribed clindamycin, while one patient received intravenous immunoglobulin (IVIg). Infective endocarditis (IE) was present in 3% of patients; however, only 44% of the total patients had an echocardiogram. The 30-day mortality rate was 13%, but it was greater in those aged > 75 years (21%). The average length of hospital stay for patients who survived was 15 days, and the average duration of intravenous therapy was 12 days. CONCLUSION: SDSE bacteraemia is typically a community-onset infection with a fifth of patients in our cohort presenting with septic shock. Though complications such as BJI (13%) and IE (3%) are infrequent, 30-day mortality is high at 21% in those aged > 75 years.

Streptococcus dysgalactiae subsp. equisimilis infection and its intersection with Streptococcus pyogenes.

SUMMARYStreptococcus dysgalactiae subsp. equisimilis (SDSE) is an increasingly recognized cause of disease in humans. Disease manifestations range from non-invasive superficial skin and soft tissue infections to life-threatening streptococcal toxic shock syndrome and necrotizing fasciitis. Invasive disease is usually associated with co-morbidities, immunosuppression, and advancing age. The crude incidence of invasive disease approaches that of the closely related pathogen, Streptococcus pyogenes. Genomic epidemiology using whole-genome sequencing has revealed important insights into global SDSE population dynamics including emerging lineages and spread of anti-microbial resistance. It has also complemented observations of overlapping pathobiology between SDSE and S. pyogenes, including shared virulence factors and mobile gene content, potentially underlying shared pathogen phenotypes. This review provides an overview of the clinical and genomic epidemiology, disease manifestations, treatment, and virulence determinants of human infections with SDSE with a particular focus on its overlap with S. pyogenes. In doing so, we highlight the importance of understanding the overlap of SDSE and S. pyogenes to inform surveillance and disease control strategies.

Insights into the enigma of oral streptococci in carcinogenesis.

SUMMARYThe genus Streptococcus consists of a taxonomically diverse group of Gram-positive bacteria that have earned significant scientific interest due to their physiological and pathogenic characteristics. Within the genus Streptococcus, viridans group streptococci (VGS) play a significant role in the oral ecosystem, constituting approximately 80% of the oral biofilm. Their primary role as pioneering colonizers in the oral cavity with multifaceted interactions like adherence, metabolic signaling, and quorum sensing contributes significantly to the complex dynamics of the oral biofilm, thus shaping oral health and disease outcomes. Perturbations in oral streptococci composition drive oral dysbiosis and therefore impact host-pathogen interactions, resulting in oral inflammation and representing VGS as an opportunistic pathogen. The association of oral streptococci in tumors across distant organs, spanning the esophagus, stomach, pancreas, and colon, illuminates a potential association between oral streptococci, inflammation, and tumorigenesis. This finding emphasizes the need for further investigations into the role of oral streptococci in mucosal homeostasis and their involvement in carcinogenesis. Hence, here, we review the significance of oral streptococci in biofilm dynamics and how the perturbation may impact mucosal immunopathogenesis in the context of cancer, with a vision of exploiting oral streptococci for cancer intervention and for the development of non-invasive cancer diagnosis.

Epidemiological Profile of Patients with Infective Endocarditis at three Tertiary Centers in Brazil from 2003 to 2017

Abstract Background Infective endocarditis (IE) is a disease with high morbimortality and an increasing incidence. With improved diagnosis and treatment, a number of epidemiological changes have been reported over time. Objectives We sought to describe the epidemiological profile, mortality predictors, and analysis of a possible microbiological transition in patients admitted to three tertiary centers in Brazil. Methods In this cross-sectional retrospective study, data from 211 patients with definite or probable IE were analyzed according to the modified Duke criteria between 2003 and 2017. The association between categorical variables was assessed using the chi-square or Fisher's exact test, and binary logistic models were built to investigate mortality. We considered p <0.05 statistically significant. Results The median age of the sample was 48 (33-59) years old, 70.6% were men, and the most prevalent pathogen was Staphylococcus spp. (19%). Mortality was 22.3%, with increasing age being the leading risk factor for death (p = 0.028). Regarding the location of the disease, native valves were the most affected site, with the aortic valve being more affected in men than women (p = 0.017). The mean number of cases of Staphylococcus spp. (τ = 0.293, p = 0.148) and Streptococcus spp. (τ = -0.078, p = 0.727) has remained stable over the years. Conclusion No trend towards reduced or increased mortality was evident between 2003 and 2017. Although Staphylococcus spp. were the most prevalent pathogen, the expected epidemiological transition could not be observed.

Hematopoietic stem and progenitor cells improve survival from sepsis by boosting immunomodulatory cells.

New therapeutic strategies to reduce sepsis-related mortality are urgently needed, as sepsis accounts for one in five deaths worldwide. Since hematopoietic stem and progenitor cells (HSPCs) are responsible for producing blood and immune cells, including in response to immunological stress, we explored their potential for treating sepsis. In a mouse model of Group A Streptococcus (GAS)-induced sepsis, severe immunological stress was associated with significant depletion of bone marrow HSPCs and mortality within approximately 5-7 days. We hypothesized that the inflammatory environment of GAS infection drives rapid HSPC differentiation and depletion that can be rescued by infusion of donor HSPCs. Indeed, infusion of 10,000 naïve HSPCs into GAS-infected mice resulted in rapid myelopoiesis and a 50-60% increase in overall survival. Surprisingly, mice receiving donor HSPCs displayed a similar pathogen load compared to untreated mice. Flow cytometric analysis revealed a significantly increased number of myeloid-derived suppressor cells in HSPC-infused mice, which correlated with reduced inflammatory cytokine levels and restored HSPC levels. These findings suggest that HSPCs play an essential immunomodulatory role that may translate into new therapeutic strategies for sepsis.

Multiple Brain Abscesses by an Air Gun Shot: A Case Report

Introduction Low-velocity penetrating brain injury is not prevalent. In some conditions such as childhood, and with the penetration of a pellet in weak spots of skull, low-velocity penetrating brain injury is expected; however, high-velocity projectiles have also been reported as the cause of severe brain injuries. One of the complications of penetrating brain injury is infection, in which different types ofmicroorganisms play a role. The Streptococcus genus is the leading cause of abscess formation in nontraumatic patients. Multiple brain abscesses are not common. Case Presentation A 10-year-old boy with penetrating brain injury caused by an air gun pellet, who developed signs and symptoms of high intracranial pressure 18 days after the trauma. After the imaging scans and the detection of multiple brain abscesses and severe brain edema, prompt surgical intervention was performed for all three lesions in a single operation. The culture of a pus specimen was positive for Streptococcus species, and, with adequate antibiotic therapy, the patient was discharged from the hospital in good condition. Conclusion Brain injurywith air gun shot is not prevalent. The penetration of a low-velocity air gun pellet in weak points of the skull (such as the orbit, the squamous portion of the temporal bone, and the cranial suture), specially in children, can cause significant brain injuries.

The immunomodulatory function of the porcine ß-defensin 129: Alleviate inflammatory response induced by LPS in IPEC-J2 cells.

ß-defensin family plays a critical role in host defense against infections. In this study, we found that pBD129 are widely expressed in porcine tissues such as the intestine, liver, and spleen. Interestingly, the expression level of pBD129 in most tissues was higher in Tibetan pigs than in DLY (Duroc × Landrace × Yorkshire) pigs (P < 0.05), and was significantly upregulated upon E. coli K88 infection (P < 0.05). The pBD129 protein was successfully expressed in E. coli and the molecule weight was estimated by SDS-PAGE to be 37.2 kDa. Mass spectrometry verified the protein as a pBD129. The protein showed antibacterial activities against Streptococcus and E. coli DH5α with a minimal inhibitory concentration (MIC) of 32 µg/mL. Hemolytic and cytotoxicity assays indicated that pBD129 had no detrimental effect on cell viability. Importantly, pBD129 significantly reduced the apoptosis of porcine intestinal epithelial cells exposure to bacterial endotoxins, which was associated with down-regulation of inflammatory cytokines such as the IL-1ß, IL-6 and TNFα (P < 0.05), and down-regulation of apoptosis-related genes such as the caspase-3, caspase-8, and caspase-9 (P < 0.05). These results suggested that pBD129 is a novel modulator of innate immunity involved in mammalian inflammatory responses.

Pathogenomics of Streptococcus ilei sp. nov., a newly identified pathogen ubiquitous in human microbiome.

Viridans group streptococci are a serious health concern because most of these bacteria cause life-threatening infections, especially in immunocompromised and hospitalized individuals. We focused on two alpha-hemolytic Streptococcus strains (I-G2 and I-P16) newly isolated from an ileostomy effluent of a colorectal cancer patient. We examined their pathogenic potential by investigating their prevalence in human and assessing their pathogenicity in a mouse model. We also predicted their virulence factors and pathogenic features by using comparative genomic analysis and in vitro tests. Using polyphasic and systematic approaches, we identified the isolates as belonging to a novel Streptococcus species and designated it as Streptococcus ilei. Metagenomic survey based on taxonomic assignment of datasets from the Human Microbiome Project revealed that S. ilei is present in most human population and at various body sites but is especially abundant in the oral cavity. Intraperitoneal injection of S. ilei was lethal to otherwise healthy C57BL/6J mice. Pathogenomics and in vitro assays revealed that S. ilei possesses a unique set of virulence factors. In agreement with the in vivo and in vitro data, which indicated that S. ilei strain I-G2 is more pathogenic than strain I-P16, only the former displayed the streptococcal group A antigen. We here newly identified S. ilei sp. nov., and described its prevalence in human, virulence factors, and pathogenicity. This will help to prevent S. ilei strain misidentification in the future, and improve the understanding and management of streptococcal infections.

Taurine Reprograms Mammary-Gland Metabolism and Alleviates Inflammation Induced by Streptococcus uberis in Mice.

Streptococcus uberis (S. uberis) is an important pathogen causing mastitis, which causes continuous inflammation and dysfunction of mammary glands and leads to enormous economic losses. Most research on infection continues to be microbial metabolism-centric, and many overlook the fact that pathogens require energy from host. Mouse is a common animal model for studying bovine mastitis. In this perspective, we uncover metabolic reprogramming during host immune responses is associated with infection-driven inflammation, particularly when caused by intracellular bacteria. Taurine, a metabolic regulator, has been shown to effectively ameliorate metabolic diseases. We evaluated the role of taurine in the metabolic regulation of S. uberis-induced mastitis. Metabolic profiling indicates that S. uberis exposure triggers inflammation and metabolic dysfunction of mammary glands and mammary epithelial cells (the main functional cells in mammary glands). Challenge with S. uberis upregulates glycolysis and oxidative phosphorylation in MECs. Pretreatment with taurine restores metabolic homeostasis, reverses metabolic dysfunction by decrease of lipid, amino acid and especially energy disturbance in the infectious context, and alleviates excessive inflammatory responses. These outcomes depend on taurine-mediated activation of the AMPK-mTOR pathway, which inhibits the over activation of inflammatory responses and alleviates cellular damage. Thus, metabolic homeostasis is essential for reducing inflammation. Metabolic modulation can be used as a prophylactic strategy against mastitis.

Inhibition of Fibrinolysis by Streptococcal Phage LysinSM1.

Expression of bacteriophage lysinSM1 by Streptococcus oralis strain SF100 is thought to be important for the pathogenesis of infective endocarditis, due to its ability to mediate bacterial binding to fibrinogen. To better define the lysinSM1 binding site on fibrinogen Aα, and to investigate the impact of binding on fibrinolysis, we examined the interaction of lysinSM1 with a series of recombinant fibrinogen Aα variants. These studies revealed that lysinSM1 binds the C-terminal region of fibrinogen Aα spanned by amino acid residues 534 to 610, with an affinity of equilibrium dissociation constant (KD) of 3.23 × 10-5 M. This binding site overlaps the known binding site for plasminogen, an inactive precursor of plasmin, which is a key protease responsible for degrading fibrin polymers. When tested in vitro, lysinSM1 competitively inhibited plasminogen binding to the αC region of fibrinogen Aα. It also inhibited plasminogen-mediated fibrinolysis, as measured by thromboelastography (TEG). These results indicate that lysinSM1 is a bi-functional virulence factor for streptococci, serving as both an adhesin and a plasminogen inhibitor. Thus, lysinSM1 may facilitate the attachment of bacteria to fibrinogen on the surface of damaged cardiac valves and may also inhibit plasminogen-mediated lysis of infected thrombi (vegetations) on valve surfaces. IMPORTANCE The interaction of streptococci with human fibrinogen and platelets on damaged endocardium is a central event in the pathogenesis of infective endocarditis. Streptococcus oralis can bind platelets via the interaction of bacteriophage lysinSM1 with fibrinogen on the platelet surface, and this process has been associated with increased virulence in an animal model of endocarditis. We now report that lysinSM1 binds to the αC region of the human fibrinogen Aα chain. This interaction blocks plasminogen binding to fibrinogen and inhibits fibrinolysis. In vivo, this inhibition could prevent the lysis of infected vegetations, thereby promoting bacterial persistence and virulence.

Prediction of Streptococcus uberis clinical mastitis treatment success in dairy herds by means of mass spectrometry and machine-learning.

Streptococcus uberis is one of the leading pathogens causing mastitis worldwide. Identification of S. uberis strains that fail to respond to treatment with antibiotics is essential for better decision making and treatment selection. We demonstrate that the combination of supervised machine learning and matrix-assisted laser desorption ionization/time of flight (MALDI-TOF) mass spectrometry can discriminate strains of S. uberis causing clinical mastitis that are likely to be responsive or unresponsive to treatment. Diagnostics prediction systems trained on 90 individuals from 26 different farms achieved up to 86.2% and 71.5% in terms of accuracy and Cohen's kappa. The performance was further increased by adding metadata (parity, somatic cell count of previous lactation and count of positive mastitis cases) to encoded MALDI-TOF spectra, which increased accuracy and Cohen's kappa to 92.2% and 84.1% respectively. A computational framework integrating protein-protein networks and structural protein information to the machine learning results unveiled the molecular determinants underlying the responsive and unresponsive phenotypes.

Psoriasis: Pathogenesis, Comorbidities, and Therapy Updated.

Psoriasis is a chronic inflammatory skin disease characterized by IL-17-dominant abnormal innate and acquired immunity, and the hyperproliferation and aberrant differentiation of epidermal keratinocytes, and comorbid arthritis or cardiometabolic diseases. This Special Issue presented updated information on pathogenesis, comorbidities, and therapy of psoriasis. The pathogenesis of psoriasis may involve the dysfunction of indoleamine 2,3-dioxygenase 2 or of UBA domain containing 1-mediated regulation of CARD14/CARMA2sh. The blood cells of psoriasis patients showed the enhanced oxidative stress/autophagy flux and decreased 20S proteasome activity. Elafin, clusterin, or selenoprotein P may act as biomarkers for psoriasis and comorbid metabolic diseases. The proteomic profile of psoriasis lesions showed the dysfunction of dermal fibroblasts; up-regulation of proinflammatory factors and signal transduction or down-regulation of structural molecules. The skin inflammation in psoriasis may populate certain gut bacteria, such as Staphylococcus aureus and Streptococcus danieliae, which worsen the skin inflammation in turn. The psoriasis-associated pruritus may be caused by immune, nervous, or vascular mechanisms. In addition to current oral treatments and biologics, a new treatment option for psoriasis is now being developed, such as retinoic-acid-receptor-related orphan nuclear receptor γt inhibitors, IL-36 receptor antagonist, or aryl hydrocarbon receptor agonist. Antimicrobial peptides and innate immune cells, involved in the pathogenesis of psoriasis, may be novel therapeutic targets. The pathomechanisms and responses to drugs in collagen diseases are partially shared with and partially different from those in psoriasis. Certain nutrients can exacerbate or regulate the progress of psoriasis. The articles in this Special Issue will encourage attractive approaches to psoriasis by future researchers.

Causative bacteria associated with a clinically relevant postoperative pancreatic fistula infection after distal pancreatectomy.

PURPOSE: Clinically relevant postoperative pancreatic fistulas (CR-POPF) occurring after distal pancreatectomy often cause intra-abdominal infections. We monitored the presence of bacterial contamination in the ascitic fluid after distal pancreatectomy to clarify the bacterial origin of intra-abdominal infections associated with CR-POPF. METHODS: In 176 patients who underwent distal pancreatectomy, ascitic fluid bacterial cultures were performed on postoperative days (POD) 1-4 and when the drainage fluid became turbid. The association between postoperative ascitic bacterial contamination and CR-POPF incidence was investigated. RESULTS: CR-POPF occurred in 18 cases (10.2%). Among the patients with CR-POPF, bacterial contamination was detected in 0% on POD 1, in 38.9% on POD 4, and in 72.2% on the day (median, day 9.5) when the drainage fluid became turbid. A univariate analysis revealed a significant difference in ascitic bacterial contamination on POD 4 (p < 0.001) and amylase level on POD 3-4 (p < 0.001). A multivariate analysis revealed the amylase level and ascitic bacterial contamination on POD 4 to be independent risk factors. CONCLUSIONS: In the CR-POPF group, ascitic bacterial contamination was not observed in the early postoperative stage, but the bacterial contamination rate increased after pancreatic juice leakage occurred. Therefore, CR-POPF-related infections in distal pancreatectomy may be caused by a retrograde infection of pancreatic juice.

Taurine Alleviates Streptococcus uberis-Induced Inflammation by Activating Autophagy in Mammary Epithelial Cells.

Streptococcus uberis infection can cause serious inflammation and damage to mammary epithelial cells and tissues that can be significantly alleviated by taurine. Autophagy plays an important role in regulating immunity and clearing invasive pathogens and may be regulated by taurine. However, the relationships between taurine, autophagy, and S. uberis infection remain unclear. Herein, we demonstrate that taurine augments PTEN activity and inhibits Akt/mTOR signaling, which decreases phosphorylation of ULK1 and ATG13 by mTOR and activates autophagy. Activating autophagy accelerates the degradation of intracellular S. uberis, reduces intracellular bacterial load, inhibits over-activation of the NF-κB pathway, and alleviates the inflammation and damage caused by S. uberis infection. This study increases our understanding of the mechanism through which taurine regulates autophagy and is the first to demonstrate the role of autophagy in S. uberis infected MAC-T cells. Our study also provides a theoretical basis for employing nutritional elements (taurine) to regulate innate immunity and control S. uberis infection. It also provides theoretical support for the development of prophylactic strategies for this important pathogen.

A multiomics approach to identify host-microbe alterations associated with infection severity in diabetic foot infections: a pilot study.

Diabetic foot infections (DFIs) are a major cause of hospitalization and can lead to lower extremity amputation. In this pilot study, we used a multiomics approach to explore the host-microbe complex within DFIs. We observed minimal differences in the overall microbial composition between PEDIS infection severities, however Staphylococcus aureus and Streptococcus genera were abundant and highly active in most mild to moderate DFIs. Further, we identified the significant enrichment of several virulence factors associated with infection pathogenicity belonging to both Staphylococcus aureus and Streptococcus. In severe DFIs, patients demonstrated a greater microbial diversity and differential gene expression demonstrated the enrichment of multispecies virulence genes suggestive of a complex polymicrobial infection. The host response in patients with severe DFIs was also significantly different as compared to mild to moderate DFIs. This was attributed to the enrichment of host genes associated with inflammation, acute phase response, cell stress and broad immune-related responses, while those associated with wound healing and myogenesis were significantly depleted.

Pathogenicity and drug resistance of animal streptococci responsible for human infections.

Bacteria of the genus Streptococcus, earlier considered typically animal, currently have also been causing infections in humans. It is necessary to make clinicians aware of the emergence of new species that may cause the development of human diseases. There is an increasing frequency of isolation of streptococci such as S. suis, S. dysgalactiae, S. iniae and S. equi from people. Isolation of Streptococcus bovis/Streptococcus equinus complex bacteria has also been reported. The streptococcal species described in this review are gaining new properties and virulence factors by which they can thrive in new environments. It shows the potential of these bacteria to changes in the genome and the settlement of new hosts. Information is presented on clinical cases that concern streptococcus species belonging to the groups Bovis, Pyogenic and Suis. We also present the antibiotic resistance profiles of these bacteria. The emerging resistance to ß-lactams has been reported. In this review, the classification, clinical characteristics and antibiotic resistance of groups and species of streptococci considered as animal pathogens are summarized.

Optimized GAPDH-truncated immunogen of Streptococcus equi elicits an enhanced immune response and provides effective protection in a mouse model.

Strangles is an acute and frequently diagnosed infectious disease caused by Streptococcus equi subsp. equi. Infection with this pathogen can cause grave losses to the equine industry. The present work investigates glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an important surface-localized virulence factor of S. equi, to determine whether it could be developed into an efficacious and suitable subunit vaccine against strangles. Two different recombinant fragments of S. equi GAPDH, namely, GAPDH-L and GAPDH-S, were constructed and expressed. Further, the antigenicity and immunogenicity of these two recombinant proteins were compared and evaluated in a mouse model. Our results revealed that immune responses were efficiently induced by the proteins in immunized mice. Remarkably, higher survival rates and significantly lower bacterial loads in the lung, liver, kidney, and spleen were observed in the GAPDH-S group compared with the GAPDH-L group after challenge with S. equi. High levels of specific antibodies, elevated antibody titers, and increased proportions of CD8 + T cells further indicated that GAPDH-S elicited better humoral and cellular immune responses than GAPDH-L. Furthermore, the induction of TCR, TLR-2, TLR-3, and TLR-4 significantly increased in the GAPDH-S group compared with those in the GAPDH-L and negative control groups. In summary, our results indicate that the optimized recombinant protein GAPDH-S is a promising candidate construct that may be further developed into a multivalent subunit vaccine for strangles.

Autoimmunity in Acute Poststreptococcal GN: A Neglected Aspect of the Disease.

Acute poststreptococcal GN (APSGN) is the prototype of immune complex GN and is associated with manifestations of autoimmune reactivity that have been neglected as epiphenomena. Recently, studies have demonstrated transient antifactor B autoantibodies that activate the alternative complement pathway, bringing self-immunity to a central position in the pathogenesis of APSGN. Therefore, examining other manifestations of autoimmunity that have been reported in association with poststreptococcal GN is of interest. This article reviews the renal and extrarenal manifestations of autoimmune reactivity in APSGN and considers their potential relevance in modifying the usually benign clinical course of the disease. It also discusses related aspects of the nephritogenic antigens, complement activation, and genetic elements associated with immune reactivity and their potential relevance to the familial incidence of the disease.