scholarly journals Streptococcus pyogenes Infection Induces Septic Arthritis with Increased Production of the Receptor Activator of the NF-κB Ligand

2003 ◽  
Vol 71 (10) ◽  
pp. 6019-6026 ◽  
Author(s):  
Atsuo Sakurai ◽  
Nobuo Okahashi ◽  
Ichiro Nakagawa ◽  
Shigetada Kawabata ◽  
Atsuo Amano ◽  
...  
Keyword(s):  
Septic Arthritis ◽  
Streptococcus Pyogenes ◽  
Group A Streptococcus ◽  
Bone Destruction ◽  
Joint Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Bacterial Arthritis ◽  
Receptor Activator ◽  
Number Of Microorganisms ◽  
Causative Agents

ABSTRACT Bacterial arthritis is a rapidly progressive and highly destructive joint disease in humans, with Staphylococcus aureus and Neisseria gonorrhoeae the major causative agents, although beta-hemolytic streptococci as well often induce the disease. We demonstrate here that intravenous inoculation of CD-1 mice with the group A streptococcus (GAS) species Streptococcus pyogenes resulted in a high incidence of septic arthritis. Signs of arthritis emerged within the first few days after injection, and bacterial examinations revealed that colonization of the inoculated GAS in the arthritic joints persisted for 21 days. Induction of persistent septic arthritis was dependent on the number of microorganisms inoculated. Immunohistochemical staining of GAS with anti-GAS antibodies revealed colonization in the joints of infected mice. Cytokine levels were quantified in the joints and sera of infected mice by using an enzyme-linked immunosorbent assay. High levels of interleukin-1β (IL-1β) and IL-6 were detected in the joints from 3 to 20 days after infection. We noted that an increase in the amount of receptor activator of NF-κB ligand (RANKL), which is a key cytokine in osteoclastogenesis, was also evident in the joints of the infected mice. RANKL was not detected in sera, indicating local production of RANKL in the infected joints. Blocking of RANKL by osteoprotegerin, a decoy receptor of RANKL, prevented bone destruction in the infected joints. These results suggest that GAS can colonize in the joints and induce bacterial arthritis. Local RANKL production in the infected joints may be involved in bone destruction.

Bone and Joint Infections

2019 ◽  
Author(s):  
Jayshree Dave ◽  
Rohma Ghani
Keyword(s):  
Septic Arthritis ◽  
Group A Streptococcus ◽  
Clinical History ◽  
Liver Function Tests ◽  
Joint Disease ◽  
Joint Fluid ◽  
Response To Treatment ◽  
Range Of Movement ◽  
Joint Infections ◽  
Bone And Joint Infections

Patients with bone and joint infections can present with native joint septic arthritis, osteomyelitis, or implant-associated bone and joint infections. Patients often present with an acute onset of hot, swollen, painful joint with restricted function in one or more joints over a couple of weeks. On examination the affected joint is painful with a limited range of movement, and fever is present. Risk factors for septic arthritis include an abnormal joint architecture due to pre-existing joint disease, e.g. patients with rheumatoid arthritis, or patients on haemodialysis, with diabetes mellitus, or older than 80 years of age. The differential diagnosis includes reactive arthritis, pre-patellar bursitis, gout, Lyme disease, brucellosis, and Whipples disease. Staphylococcus aureus is the most common cause of septic arthritis, followed by Group A streptococcus and other haemolytic streptococci including B, C and G. Gram-negative rods such as Escherichia coli are implicated in the elderly, immunosuppressed, or patients with comorbidities. Pseudomonas aeruginosa is implicated in intravenous (IV) drug users and patients post-surgery or intra-articular injections. Kingella kingae causes septic arthritis in children younger than four years of age. Neisseria gonorrhoeae, Neisseria meningitidis, and Salmonella species can also cause septic arthritis as part of a disseminated infection. Septic monoarthritis commonly occurs in patients with disseminated gonococcal infection. Blood cultures, white blood cell count, C reactive protein (CRP), electrolytes, and liver function tests are indicated. Serial CRP is useful in monitoring response to treatment. If there is a history of unprotected sexual intercourse, gonococcal testing is recommended. Brucella serology and Tropheryma whippei serology may be considered based on the clinical history. Joint fluid aspiration should be performed by a specialist within the hospital. Joint fluid aspirate is processed in the laboratory for microscopy, culture, and sensitivity. Gram stain can show an increase in neutrophils and presence of bacteria. The guidelines provided by the British Society for Rheumatology on the management of hot swollen joints in adults has provided advice for empirical treatment for suspected septic arthritis, but the local antibiotic policy should also be considered. Initial treatment is with intravenous flucloxacillin 2g four times daily, or 450– 600mg four times daily of intravenous clindamycin to cover S. aureus.

scholarly journals Infection by Streptococcus pyogenes Induces the Receptor Activator of NF-κB Ligand Expression in Mouse Osteoblastic Cells

2003 ◽  
Vol 71 (2) ◽  
pp. 948-955 ◽  
Author(s):  
Nobuo Okahashi ◽  
Atsuo Sakurai ◽  
Ichiro Nakagawa ◽  
Taku Fujiwara ◽  
Shigetada Kawabata ◽  
...  
Keyword(s):  
Western Blot ◽  
Streptococcus Pyogenes ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Bone Cells ◽  
Specific Inhibitor ◽  
Bone Destruction ◽  
Mitogen Activated Protein Kinase ◽  
No Production ◽  
Receptor Activator

ABSTRACT Group A Streptococcus pyogenes is known to induce nongonococcal septic arthritis in addition to pharyngitis, scarlet fever, and poststreptococcal sequelae. However, little is known about the interaction between S. pyogenes and bone cells. We report here that S. pyogenes strain JRS4 (M6) attached to and invaded mouse primary osteoblasts. Reverse transcription-PCR demonstrated that S. pyogenes infection of osteoblasts stimulated expression of mRNA for the receptor activator of NF-κB ligand (RANKL). Western blot analysis followed by ligand precipitation with the receptor activator of NF-κB receptor showed that there was an increase in RANKL protein in infected osteoblasts. Production of interleukin-6 was also stimulated, but no production of interleukin-1β or tumor necrosis factor alpha was observed. Stimulation of RANKL production was not observed in osteoblasts stimulated with heat-inactivated S. pyogenes, suggesting that an active interaction of S. pyogenes with osteoblasts is essential for this phenomenon. A Western blot analysis performed with antibodies specific for phosphorylated signal transduction proteins demonstrated that S. pyogenes infection induces phosphorylation of p38 mitogen-activated protein kinase. A specific inhibitor of this kinase, SB203580, inhibited RANKL production by infected osteoblasts. These results suggest that infection of osteoblasts by S. pyogenes stimulates RANKL production and may trigger bone destruction in infected bone tissue.

scholarly journals Degenerative Joint Damage Is Not a Risk Factor for Streptococcal Sepsis and Septic Arthritis in Mice

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 794
Author(s):  
Johann Volzke ◽  
Brigitte Müller-Hilke
Keyword(s):  
Risk Factor ◽  
Septic Arthritis ◽  
Bone Structure ◽  
Group A Streptococcus ◽  
Cruciate Ligament ◽  
Clinical Signs ◽  
Joint Damage ◽  
Joint Disease ◽  
Micro Computed Tomography ◽  
Bone Morphology

Septic arthritis (SA) is an aggressive joint disorder causing invalidity and mortality. Although epidemiological studies suggest osteoarthritis (OA) as a risk factor for SA, experimental insights into the relatedness of both diseases are lacking. We therefore sought to investigate whether pre-existing OA indeed promotes SA frequency or severity. We used STR/ort mice that spontaneously develop OA and, in addition, induced OA via anterior cruciate ligament transection (ACLT) in C57BL/6J mice. Mice were infected with Group A Streptococcus (GAS) and then were monitored for clinical signs of sepsis and SA. Sepsis was confirmed via elevated inflammatory cytokines in plasma, while bone morphology was assessed by micro-computed tomography. Cartilage integrity was evaluated histologically. Mice with spontaneous OA developed life-threatening SA, with GAS only moderately affecting the femoral bone structure. Surgically induced OA neither impacted on SA incidence nor on mortality when compared to infected mice without the preceding joint disease. Furthermore, only insignificant differences in bone morphology were detected between both groups. Our data indicate that degenerative joint damage due to ACLT, by itself, does not predispose mice to SA. Hence, we propose that other factors such as prosthetic joint replacement or high age, which frequently coincide with OA, pose a risk for SA development.

scholarly journals An 18 year clinical review of septic arthritis from tropical Australia

1996 ◽  
Vol 117 (3) ◽  
pp. 423-428 ◽  
Author(s):  
D. S. Morgan ◽  
D. Fisher ◽  
A. Merianos ◽  
B. J. Currie
Keyword(s):  
Staphylococcus Aureus ◽  
Septic Arthritis ◽  
Streptococcus Pyogenes ◽  
Needle Aspiration ◽  
Joint Disease ◽  
Medical Illness ◽  
Treatment Procedure ◽  
Aboriginal Australians ◽  
Tropical Australia ◽  
Open Arthrotomy

SummaryA retrospective study of 191 cases of septic arthritis was undertaken at Royal Darwin Hospital in the tropical north of Australia. Incidence was 9·2 per 100000 overall and 29·1 per 100000 in Aboriginal Australians (RR 6·6; 95% CI 5·0–8·9). Males were affected more than females (RR 1·6; 95% CI 1·2–2·1). There was no previous joint disease or medical illness in 54%. The commonest joints involved were the knee (54%) and hip (13%). Significant age associations were infected hips in those under 15 years and infected knees in those over 45 years. Seventy-two percent of infections were haematogenous. Causative organisms included Staphylococcus aureus (37%),Streptococcus pyogenes(16%) andNeisseria gonorrhoeae(12%). Unusual infections included three melioidosis cases. Polyarthritis occurred in 17%, withN. gonorrhoeae(11/23) more likely to present as polyarthritis than other organisms (22/168) (OR 6·0; 95% CI 2·1–16·7). Univariate and multivariate analysis showed the hip to be at greater risk forS. aureusthan other joints. Open arthrotomy was a more successful treatment procedure than arthroscopic washout or needle aspiration.

Etiology, clinical presentation, laboratory diagnostics, pathogenesis of impetigo and treatment methods

2020 ◽  
pp. 64-70
Author(s):  
Anastasiya Laknitskaya
Keyword(s):  
Streptococcus Pyogenes ◽  
Skin Diseases ◽  
Group A Streptococcus ◽  
Antibiotic Sensitivity ◽  
Antioxidant Defense System ◽  
Laboratory Diagnostics ◽  
Treatment Methods ◽  
Group A ◽  
The Individual

Currently, one of the priority medical and social problems is the optimization of treatment methods for pyoderma associated with Streptococcus pyogenes — group A streptococcus (GAS). To date, the proportion of pyoderma, the etiological factor of which is Streptococcus pyogenes, is about 6 % of all skin diseases and is in the range from 17.9 to 43.9 % of all dermatoses. Role of the bacterial factor in the development of streptococcal pyoderma is obvious. Traditional treatment complex includes antibacterial drugs selected individually, taking into account the antibiotic sensitivity of pathognomonic bacteria, and it is not always effective. Currently implemented immunocorrection methods often do not take into account specific immunological features of the disease, the individual, and the fact that the skin performs the function of not only a mechanical barrier, but it is also an immunocompetent organ. Such an approach makes it necessary to conduct additional studies clarifying the role of factors of innate and adaptive immunity, intercellular mediators and antioxidant defense system, that allow to optimize the treatment of this pathology.

The Impact of Proinflammatory Cytokynes of Rheumatoid Polyarthritis on the Generalized Loss of Bone Mass

2018 ◽  
Vol 69 (9) ◽  
pp. 2541-2545
Author(s):  
Raluca Barzoi ◽  
Elena Rezus ◽  
Codruta Badescu ◽  
Razan Al Namat ◽  
Manuela Ciocoiu
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Cells ◽  
Osteoclast Differentiation ◽  
Bone Destruction ◽  
Nuclear Factor ◽  
Receptor Activator ◽  
Level Function ◽  
Rheumatoid Polyarthritis ◽  
The Impact ◽  
Nuclear Factor Kb

There is a bidirectional interaction between most immune cells and osteoblasts, osteoclasts and their precursor cells. The receptor activator of nuclear factor-kB ligand (RANKL)/RANK/osteoprotegerin (OPG) system plays an essential role in the formation of osteoblasts, but it also has implications in osteoclast biology and implicitly on the diseases characterized by bone loss. Proinflammatory cytokines existing at synovial level function as direct or indirect stimulators of osteoclast differentiation, but also of its survival or activity, although some cytokines may also play an antiosteocastogenic role. The fate of bone destruction is determined by the balance between osteoclastogenic and antiosteoclastogenic mediators. Our study has shown that the early initiation of the therapy with anti-TNF and anti-IL6 biological agents, in patients with rheumatoid arthritis, inhibits bone destruction, regardless of the anti-inflammatory activity in patients with rheumatoid arthritis.

Treatment with Melittin Induces Apoptosis and Autophagy of Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis

2020 ◽  
Vol 21 (8) ◽  
pp. 734-740 ◽  
Author(s):  
Shou-di He ◽  
Ning Tan ◽  
Chen-xia Sun ◽  
Kang-han Liao ◽  
Hui-jun Zhu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Caspase 3 ◽  
Joint Destruction ◽  
Joint Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Caspase 9 ◽  
Inflammatory Processes ◽  
Related Proteins ◽  
Local Stimulation ◽  
Fibroblast Like Synoviocytes

Background: Melittin, the major medicinal component of honeybee venom, exerts antiinflammatory, analgesic, and anti-arthritic effects in patients with Rheumatoid Arthritis (RA). RA is an inflammatory autoimmune joint disease that leads to irreversible joint destruction and functional loss. Fibroblast-Like Synoviocytes (FLS) are dominant, special mesenchymal cells characterized by the structure of the synovial intima, playing a crucial role in both the initiation and progression of RA. Objective: In this study, we evaluated the effects of melittin on the viability and apoptosis of FLS isolated from patients with RA. Methods: Cell viability was determined using CCK-8 assays; apoptosis was evaluated by flow cytometry, and the expression levels of apoptosis-related proteins (caspase-3, caspase-9, BAX, and Bcl-2) were also determined. To explore whether melittin alters inflammatory processes in RA-FLS, IL-1β levels were determined using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we performed GFP-LC3 punctate fluorescence dot assays and western blotting (for LC3, ATG5, p62, and Beclin 1) to assess autophagy in RA-FLS. Results: Our results show that melittin can significantly impair viability, promote apoptosis and autophagy, and inhibit IL-1β secretion in RA-FLS. Conclusion: Melittin may be useful in preventing damage to the joints during accidental local stimulation.

scholarly journals Pediatric Septic Arthritis of the Knee Due to a Multi-Sensitive Streptococcus pyogenes Strain Responsive to Clindamycin—A Case Report

Children ◽  
2021 ◽  
Vol 8 (3) ◽  
pp. 189
Author(s):  
Giada Maria Di Pietro ◽  
Irene Maria Borzani ◽  
Sebastiano Aleo ◽  
Samantha Bosis ◽  
Paola Marchisio ◽  
...  
Keyword(s):  
Septic Arthritis ◽  
Streptococcus Pyogenes ◽  
Antibiotic Sensitivity ◽  
Antimicrobial Treatment ◽  
Antibiotic Regimen ◽  
Hematogenous Spread ◽  
Clinical Resistance ◽  
Antibiotic Sensitivity Test ◽  
Clinical Conditions

Septic arthritis is an inflammatory process usually generated by a bacterial infection. The knee is one of the most frequently involved joints. The etiology varies depending on age, and hematogenous spread remains the primary cause in children. Herein, we report a case of a previously healthy three-year-old female who was referred to our institution for acute swelling of her right knee. After a clinical and radiological diagnosis of septic arthritis, an empirical treatment with a combination of cefotaxime and clindamycin was initiated. The isolation of a multi-sensitive Streptococcus pyogenes strain from the joint’s effusion prompted the discontinuation of clindamycin and the usage of cefotaxime alone. One week later, an ultrasound was executed due to worsening in the patient’s clinical conditions, and an organized corpuscular intra-articular effusion with diffuse synovial thickening was revealed. Cefotaxime was therefore replaced with clindamycin, which improved the symptoms. Despite the antibiotic sensitivity test having revealed a microorganism with sensitivity to both cephalosporin and clindamycin, clinical resistance to cefotaxime was encountered and a shift in the antimicrobial treatment was necessary to ensure a full recovery. This case study confirms that an antibiotic regimen based solely on a susceptibility test may be ineffective for such cases.

scholarly journals Association between Resistance to Erythromycin and the Presence of the Fibronectin Binding Protein F1 Gene, prtF1, in Streptococcus pyogenes Isolates from German Pediatric Patients

2005 ◽  
Vol 49 (7) ◽  
pp. 2990-2993 ◽  
Author(s):  
Maria Haller ◽  
Kirsten Fluegge ◽  
Sandra Jasminder Arri ◽  
Brit Adams ◽  
Reinhard Berner
Keyword(s):  
Streptococcus Pyogenes ◽  
Pediatric Patients ◽  
Group A Streptococcus ◽  
Binding Protein ◽  
Macrolide Resistance ◽  
Group A ◽  
Fibronectin Binding Protein ◽  
Fibronectin Binding ◽  
Cell Invasiveness

ABSTRACT A total of 301 German pediatric group A streptococcus isolates were screened for the presence of macrolide resistance and the fibronectin binding protein F1 gene (prtF1) encoding an adhesin and cell invasiveness protein. The prtF1 gene was present significantly more often among macrolide-resistant isolates. The majority of these were not clonally related.

scholarly journals The Transcriptional Regulator CpsY Is Important for Innate Immune Evasion in Streptococcus pyogenes

2016 ◽  
Vol 85 (3) ◽  
Author(s):  
Luis A. Vega ◽  
Kayla M. Valdes ◽  
Ganesh S. Sundar ◽  
Ashton T. Belew ◽  
Emrul Islam ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Immune Evasion ◽  
Immune Cell ◽  
Group A Streptococcus ◽  
Transcriptional Regulator ◽  
Innate Immune ◽  
Content Type ◽  
Human Host

ABSTRACTAs an exclusively human pathogen,Streptococcus pyogenes(the group A streptococcus [GAS]) has specifically adapted to evade host innate immunity and survive in multiple tissue niches, including blood. GAS can overcome the metabolic constraints of the blood environment and expresses various immunomodulatory factors necessary for survival and immune cell resistance. Here we present our investigation of one such factor, the predicted LysR family transcriptional regulator CpsY. The encoding gene,cpsY, was initially identified as being required for GAS survival in a transposon-site hybridization (TraSH) screen in whole human blood. CpsY is homologous with transcriptional regulators ofStreptococcus mutans(MetR),Streptococcus iniae(CpsY), andStreptococcus agalactiae(MtaR) that regulate methionine transport, amino acid metabolism, resistance to neutrophil-mediated killing, and survivalin vivo. Our investigation indicated that CpsY is involved in GAS resistance to innate immune cells of its human host. However, GAS CpsY does not manifest thein vitrophenotypes of its homologs in other streptococcal species. GAS CpsY appears to regulate a small set of genes that is markedly different from the regulons of its homologs. The differential expression of these genes depends on the growth medium, and CpsY modestly influences their expression. The GAS CpsY regulon includes known virulence factors (mntE,speB,spd,nga[spn],prtS[SpyCEP], andsse) and cell surface-associated factors of GAS (emm1,mur1.2,sibA[cdhA], andM5005_Spy0500). Intriguingly, the loss of CpsY in GAS does not result in virulence defects in murine models of infection, suggesting that CpsY function in immune evasion is specific to the human host.

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