Immunopathological mechanisms in bacterial-host interactions

1983 ◽  
Vol 303 (1114) ◽  
pp. 177-187 ◽  
Keyword(s):  
Rheumatic Fever ◽  
Group A Streptococcus ◽  
Biological Properties ◽  
Antigenic Determinants ◽  
Bacterial Host ◽  
Poststreptococcal Glomerulonephritis ◽  
Host Interactions ◽  
Disease States ◽  
Group A ◽  
Specific Tissue

The ability of bacteria to cause immunopathological damage in the host may take a variety of forms. These pathways may be conveniently grouped under three major headings: (1) organisms that can cause damage via shared antigenic determinants between host and bacterium; (2) those organisms that suppress the host’s response; and (3) organisms that release substances with specific biological properties or have receptors for specific tissue sites. The group A streptococcus is among the most versatile of these bacteria because it appears that it may use all three pathways in various streptococcal-related disease states. In rheumatic fever and chorea it appears that cross-reactive antigens play a major role in inducing immunopathological damage in that there is both a heightened humoral and cellular reaction by the host to these cross-reactive determinants. Recent evidence also indicates that rheumatic fever individuals express certain B cell antigens that may be associated with susceptibility to the disease. In the other complications of streptococcal infections, namely poststreptococcal glomerulonephritis, the bacterium uses both suppression of the host’s immune response and the excretion of a particular protein common to all nephritis-associated strains to achieve its immunopathological damage. In this context, other examples of bacterial-host interactions will be discussed as evidence for the common pathways used by microbes to cause immunopathological damage in the host.

scholarly journals A brief review on Group A Streptococcus pathogenesis and vaccine development

2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Sowmya Ajay Castro ◽  
Helge C. Dorfmueller
Keyword(s):  
Rheumatic Fever ◽  
Prolonged Exposure ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Streptococcal Toxic Shock Syndrome ◽  
Host Immune System ◽  
Industrialized Countries ◽  
Poststreptococcal Glomerulonephritis ◽  
Group A ◽  
The Impact

Streptococcus pyogenes , also known as Group A Streptococcus (GAS), is a Gram-positive human-exclusive pathogen, responsible for more than 500 000 deaths annually worldwide. Upon infection, GAS commonly triggers mild symptoms such as pharyngitis, pyoderma and fever. However, recurrent infections or prolonged exposure to GAS might lead to life-threatening conditions. Necrotizing fasciitis, streptococcal toxic shock syndrome and post-immune mediated diseases, such as poststreptococcal glomerulonephritis, acute rheumatic fever and rheumatic heart disease, contribute to very high mortality rates in non-industrialized countries. Though an initial reduction in GAS infections was observed in high-income countries, global outbreaks of GAS, causing rheumatic fever and acute poststreptococcal glomerulonephritis, have been reported over the last decade. At the same time, our understanding of GAS pathogenesis and transmission has vastly increased, with detailed insight into the various stages of infection, beginning with adhesion, colonization and evasion of the host immune system. Despite deeper knowledge of the impact of GAS on the human body, the development of a successful vaccine for prophylaxis of GAS remains outstanding. In this review, we discuss the challenges involved in identifying a universal GAS vaccine and describe several potential vaccine candidates that we believe warrant pursuit.

scholarly journals Group a streptococcal antigens cross-reactive with myocardium. Purification of heart-reactive antibody and isolation and characterization of the streptococcal antigen

1977 ◽  
Vol 146 (2) ◽  
pp. 579-599 ◽  
Author(s):  
I Van De Rijn ◽  
JB Sabriskie ◽  
M McCarty
Keyword(s):  
Rheumatic Fever ◽  
Group A Streptococcus ◽  
Proteolytic Enzymes ◽  
Sodium Dodecyl ◽  
Antigenic Determinants ◽  
Isolation And Characterization ◽  
Nonionic Detergent ◽  
Group A ◽  
Purified Antigen ◽  
Reactive Antibody

Heart-reactive antibody (HRA) appears in the sera of experimental animals inoculated with group A streptococci as well as patients with acute rheumatic fever. Adsorption of either serum with group A streptococcal membranes will remove the HRA. Blocking experiments between these two types of HRAs have demonstrated that the antibodies are directed towards different antigenic determinants on either the same or different molecules. To isolate and purify the antigen from the group A streptococcus cross-reactive with sarcolemmal sheaths of cardiac myofibers, it became necessary to purify the HRA from rheumatic fever patients' sera. Isolated gamma globulin containing all of the HRA was adsorbed onto human sarcolemmal sheaths. The specific HRA was released by using potassium iodide. Over 99 percent of the purified HRA was shown to bind the sarcolemmal sheath whereas less than 1 percent of the antibody would bind nonspecifically to other material. Preparations of group A streptococcal membrane will bind HRA purified from the sera of acute rheumatic patients at levels of 97 percent or greater. The cross-reactive antigen solubilized by nonionic detergent was purified 120-fold by column chromatography. On sodium dodecyl sulfate polyacrylamide electrophoresis, the antigen was demonstrated to be composed of four polypeptides with mol wt of 32,000, 28,000, 26,000, and 22,000 daltons, respectively. Only proteolytic enzymes could destroy the antigenic determinant whereas glycosidases and lipases had no effect. The purified antigen blocked the binding of purified HRA to normal human heart sections.

Rheumatic Fever Article Questioned

PEDIATRICS ◽  
1984 ◽  
Vol 74 (6) ◽  
pp. 1133-1134
Author(s):  
SYLVIA P. GRIFFITHS
Keyword(s):  
Rheumatic Fever ◽  
Intramuscular Injection ◽  
Group A Streptococcus ◽  
Penicillin G ◽  
Benzathine Penicillin ◽  
Benzathine Penicillin G ◽  
Group A

To the Editor.— The suggestion of Nordin1 that there may be a need to re-evaluate the current recommended prophylaxis for children with rheumatic fever is valid, particularly if carefully planned and controlled studies could be carried out. However, the author's contention that "It has been assumed that the levels of penicillin [following monthly intramuscular injection of 1.2 million units of benzathine penicillin G] are adequate to prevent reinfection with group A streptococcus, and hence to prevent recurrences of rheumatic fever" has always been qualified by others.

Group A streptococcus, pyoderma, and rheumatic fever

The Lancet ◽  
1996 ◽  
Vol 347 (9010) ◽  
pp. 1271-1272 ◽  
Author(s):  
JonathanR. Carapetis ◽  
BartJ. Currie
Keyword(s):  
Rheumatic Fever ◽  
Group A Streptococcus ◽  
Group A

scholarly journals Identification of Group A Streptococcus Antigenic Determinants Upregulated In Vivo

2005 ◽  
Vol 73 (9) ◽  
pp. 6026-6038 ◽  
Author(s):  
Kowthar Y. Salim ◽  
Dennis G. Cvitkovitch ◽  
Peter Chang ◽  
Darrin J. Bast ◽  
Martin Handfield ◽  
...  
Keyword(s):  
Murine Model ◽  
Vibrio Vulnificus ◽  
Group A Streptococcus ◽  
Hypothetical Protein ◽  
Invasive Disease ◽  
Antigenic Determinants ◽  
Expression Library ◽  
Group A

ABSTRACT Group A Streptococcus (GAS) causes a range of diseases in humans, from mild noninvasive infections to severe invasive infections. The molecular basis for the varying severity of disease remains unclear. We identified genes expressed during invasive disease using in vivo-induced antigen technology (IVIAT), applied for the first time in a gram-positive organism. Convalescent-phase sera from patients with invasive disease were pooled, adsorbed against antigens derived from in vitro-grown GAS, and used to screen a GAS genomic expression library. A murine model of invasive GAS disease was included as an additional source of sera for screening. Sequencing DNA inserts from clones reactive with both human and mouse sera indicated 16 open reading frames with homology to genes involved in metabolic activity to genes of unknown function. Of these, seven genes were assessed for their differential expression by quantitative real-time PCR both in vivo, utilizing a murine model of invasive GAS disease, and in vitro at different time points of growth. Three gene products—a putative penicillin-binding protein 1A, a putative lipoprotein, and a conserved hypothetical protein homologous to a putative translation initiation inhibitor in Vibrio vulnificus—were upregulated in vivo, suggesting that these genes play a role during invasive disease.

Acute Rheumatic Fever After Group A Streptococcus Pyoderma and Group G Streptococcus Pharyngitis

2017 ◽  
Vol 36 (7) ◽  
pp. 692-694 ◽  
Author(s):  
Lance O’Sullivan ◽  
Nicole J. Moreland ◽  
Rachel H. Webb ◽  
Arlo Upton ◽  
Nigel J. Wilson
Keyword(s):  
Rheumatic Fever ◽  
Acute Rheumatic Fever ◽  
Group A Streptococcus ◽  
Group A

Cysteine proteinase SpeB from Streptococcus pyogenes – a potent modifier of immunologically important host and bacterial proteins

2011 ◽  
Vol 392 (12) ◽  
pp. 1077-1088 ◽  
Author(s):  
Daniel C. Nelson ◽  
Julia Garbe ◽  
Mattias Collin
Keyword(s):  
Streptococcus Pyogenes ◽  
Group A Streptococcus ◽  
Wide Spectrum ◽  
Cysteine Proteinase ◽  
Complement Components ◽  
Bacterial Surface ◽  
Bacterial Proteins ◽  
Disease States ◽  
Group A ◽  
Important Host

AbstractGroup A streptococcus (Streptococcus pyogenes) is an exclusively human pathogen that causes a wide spectrum of diseases ranging from pharyngitis, to impetigo, to toxic shock, to necrotizing fasciitis. The diversity of these disease states necessitates thatS. pyogenespossess the ability to modulate both the innate and adaptive immune responses. SpeB, a cysteine proteinase, is the predominant secreted protein fromS. pyogenes. Because of its relatively indiscriminant specificity, this enzyme has been shown to degrade the extracellular matrix, cytokines, chemokines, complement components, immunoglobulins, and serum protease inhibitors, to name but a few of the known substrates. Additionally, SpeB regulates other streptococcal proteins by degrading them or releasing them from the bacterial surface. Despite the wealth of literature on putative SpeB functions, there remains much controversy about this enzyme because many of reported activities would produce contradictory physiological results. Here we review all known host and bacterial protein substrates for SpeB, their cleavage sites, and discuss the role of this enzyme in streptococcal pathogenesis based on the current literature.

scholarly journals Characterization of Two Novel Pyrogenic Toxin Superantigens Made by an Acute Rheumatic Fever Clone of Streptococcus pyogenes Associated with Multiple Disease Outbreaks

2002 ◽  
Vol 70 (12) ◽  
pp. 7095-7104 ◽  
Author(s):  
Laura M. Smoot ◽  
John K. McCormick ◽  
James C. Smoot ◽  
Nancy P. Hoe ◽  
Ian Strickland ◽  
...  
Keyword(s):  
Rheumatic Fever ◽  
Acute Rheumatic Fever ◽  
Mononuclear Cells ◽  
Group A Streptococcus ◽  
Human Peripheral Blood ◽  
Disease Outbreaks ◽  
Peripheral Blood Mononuclear ◽  
Human T Cells ◽  
Group A

ABSTRACT The pathogenesis of acute rheumatic fever (ARF) is poorly understood. We identified two contiguous bacteriophage genes, designated speL and speM, encoding novel inferred superantigens in the genome sequence of an ARF strain of serotype M18 group A streptococcus (GAS). speL and speM were located at the same genomic site in 33 serotype M18 isolates, and no nucleotide sequence diversity was observed in the 33 strains analyzed. Furthermore, the genes were absent in 13 non-M18 strains tested. These data indicate a recent acquisition event by a distinct clone of serotype M18 GAS. speL and speM were transcribed in vitro and upregulated in the exponential phase of growth. Purified SpeL and SpeM were pyrogenic and mitogenic for rabbit splenocytes and human peripheral blood mononuclear cells in picogram amounts. SpeL preferentially expanded human T cells expressing T-cell receptors Vβ1, Vβ5.1, and Vβ23, and SpeM had specificity for Vβ1 and Vβ23 subsets, indicating that both proteins had superantigen activity. SpeL was lethal in two animal models of streptococcal toxic shock, and SpeM was lethal in one model. Serologic studies indicated that ARF patients were exposed to serotype M18 GAS, SpeL, and SpeM. The data demonstrate that SpeL and SpeM are pyrogenic toxin superantigens and suggest that they may participate in the host-pathogen interactions in some ARF patients.

scholarly journals The Role of Nephritis-Associated Plasmin Receptor (NAPlr) in Glomerulonephritis Associated with Streptococcal Infection

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Takashi Oda ◽  
Nobuyuki Yoshizawa ◽  
Kazuo Yamakami ◽  
Yutaka Sakurai ◽  
Hanako Takechi ◽  
...  
Keyword(s):  
Renal Biopsy ◽  
Streptococcal Infection ◽  
Group A Streptococcus ◽  
Plasmin Activity ◽  
Subsequent Formation ◽  
Poststreptococcal Glomerulonephritis ◽  
Circulating Antigen ◽  
Group A ◽  
Antigen Antibody

It is well known that glomerulonephritis can occur after streptococcal infection, which is classically referred to as acute poststreptococcal glomerulonephritis (APSGN). The pathogenic mechanism of APSGN has been described by so-called immune complex theory, which involves glomerular deposition of nephritogenic streptococcal antigen and subsequent formation of immune complexesin situand/or the deposition of circulating antigen-antibody complexes. However, the exact entity of the causative antigen has remained a matter of debate. We isolated a nephritogenic antigen for APSGN from the cytoplasmic fractions of group A streptococcus (GAS) depending on the affinity for IgG of APSGN patients. The amino acid and the nucleotide sequences of the isolated protein revealed to be highly identical to those of reported plasmin(ogen) receptor of GAS. Thus, we termed this antigen nephritis-associated plasmin receptor (NAPlr). Immunofluorescence staining of the renal biopsy tissues with anti-NAPlr antibody revealed glomerular NAPlr deposition in essentially all patients with early-phase APSGN. Furthermore, glomerular plasmin activity was detected byin situzymography in the distribution almost identical to NAPlr deposition in renal biopsy tissues of APSGN patients. These data suggest that NAPlr has a direct, nonimmunologic function as a plasmin receptor and may contribute to the pathogenesis of APSGN by maintaining plasmin activity.

scholarly journals Delayed Diagnosis of Acute Rheumatic Fever in a Patient with Multiple Emergency Department Visits

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Inna Kaminecki ◽  
Renuka Verma ◽  
Jacqueline Brunetto ◽  
Loyda I. Rivera
Keyword(s):  
Emergency Department ◽  
Rheumatic Fever ◽  
Health Care Providers ◽  
Acute Rheumatic Fever ◽  
Group A Streptococcus ◽  
The United States ◽  
Emergency Department Visits ◽  
Penicillin G ◽  
Care Providers ◽  
Group A

While the incidence of acute rheumatic fever (ARF) in the United States has declined over the past years, the disease remains one of the causes of severe cardiovascular morbidity in children. The index of suspicion for ARF in health care providers may be low due to decreasing incidence of the disease and clinical presentation that can mimic other conditions. We present the case of a 5-year-old boy with a history of intermittent fevers, fatigue, migratory joint pain, and weight loss followinggroup A Streptococcuspharyngitis. The patient presented to the emergency department twice with the complaints described above. On his 3rd presentation, the workup for his symptoms revealed the diagnosis of acute rheumatic fever with severe mitral and aortic valve regurgitation. The patient was treated with penicillin G benzathine and was started on glucocorticoids for severe carditis. The patient was discharged with recommendations to continue secondary prophylaxis with penicillin G benzathine every 4 weeks for the next 10 years. This case illustrates importance of primary prevention of acute rheumatic fever with adequate antibiotic treatment ofgroup A Streptococcuspharyngitis. Parents should also receive information and education that a child with a previous attack of ARF has higher risk for a recurrent attack of rheumatic fever. This can lead to development of severe rheumatic heart disease. Prevention of recurrent ARF requires continuous antimicrobial prophylaxis. Follow-up with a cardiologist every 1-2 years is essential to assess the heart for valve damage.

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