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.

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 Molecular Epidemiology of Group A Streptococcus Infections in The Gambia

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 124
Author(s):  
Sona Jabang ◽  
Annette Erhart ◽  
Saffiatou Darboe ◽  
Aru-Kumba Baldeh ◽  
Valerie Delforge ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Epidemiological Data ◽  
The Gambia ◽  
Strain Diversity ◽  
Group A ◽  
Considerable Strain

Molecular epidemiological data on Group A Streptococcus (GAS) infection in Africa is scarce. We characterized the emm-types and emm-clusters of 433 stored clinical GAS isolates from The Gambia collected between 2004 and 2018. To reduce the potential for strain mistyping, we used a newly published primer for emm-typing. There was considerable strain diversity, highlighting the need for vaccine development offering broad strain protection.

scholarly journals A Two-Component Regulatory System Impacts Extracellular Membrane-Derived Vesicle Production in Group A Streptococcus

mBio ◽  
2016 ◽  
Vol 7 (6) ◽  
Author(s):  
Ulrike Resch ◽  
James Anthony Tsatsaronis ◽  
Anaïs Le Rhun ◽  
Gerald Stübiger ◽  
Manfred Rohde ◽  
...  
Keyword(s):  
Lipid Composition ◽  
Secretory Pathway ◽  
Group A Streptococcus ◽  
Regulatory System ◽  
Surface Proteins ◽  
Streptococcal Toxic Shock Syndrome ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Two Component ◽  
Group A

ABSTRACT Export of macromolecules via extracellular membrane-derived vesicles (MVs) plays an important role in the biology of Gram-negative bacteria. Gram-positive bacteria have also recently been reported to produce MVs; however, the composition and mechanisms governing vesiculogenesis in Gram-positive bacteria remain undefined. Here, we describe MV production in the Gram-positive human pathogen group A streptococcus (GAS), the etiological agent of necrotizing fasciitis and streptococcal toxic shock syndrome. M1 serotype GAS isolates in culture exhibit MV structures both on the cell wall surface and in the near vicinity of bacterial cells. A comprehensive analysis of MV proteins identified both virulence-associated protein substrates of the general secretory pathway in addition to “anchorless surface proteins.” Characteristic differences in the contents, distributions, and fatty acid compositions of specific lipids between MVs and GAS cell membrane were also observed. Furthermore, deep RNA sequencing of vesicular RNAs revealed that GAS MVs contained differentially abundant RNA species relative to bacterial cellular RNA. MV production by GAS strains varied in a manner dependent on an intact two-component system, CovRS, with MV production negatively regulated by the system. Modulation of MV production through CovRS was found to be independent of both GAS cysteine protease SpeB and capsule biosynthesis. Our data provide an explanation for GAS secretion of macromolecules, including RNAs, lipids, and proteins, and illustrate a regulatory mechanism coordinating this secretory response. IMPORTANCE Group A streptococcus (GAS) is a Gram-positive bacterial pathogen responsible for more than 500,000 deaths annually. Establishment of GAS infection is dependent on a suite of proteins exported via the general secretory pathway. Here, we show that GAS naturally produces extracellular vesicles with a unique lipid composition that are laden with proteins and RNAs. Interestingly, both virulence-associated proteins and RNA species were found to be differentially abundant in vesicles relative to the bacteria. Furthermore, we show that genetic disruption of the virulence-associated two-component regulator CovRS leads to an increase in vesicle production. This study comprehensively describes the protein, RNA, and lipid composition of GAS-secreted MVs and alludes to a regulatory system impacting this process.

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.

scholarly journals Streptococcus pyogenes evades adaptive immunity through specific IgG glycan hydrolysis

2019 ◽  
Vol 216 (7) ◽  
pp. 1615-1629 ◽  
Author(s):  
Andreas Naegeli ◽  
Eleni Bratanis ◽  
Christofer Karlsson ◽  
Oonagh Shannon ◽  
Raja Kalluru ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Invasive Infection ◽  
Invasive Infections ◽  
Life Threatening ◽  
Group A ◽  
Specific Igg

Streptococcus pyogenes (Group A streptococcus; GAS) is a human pathogen causing diseases from uncomplicated tonsillitis to life-threatening invasive infections. GAS secretes EndoS, an endoglycosidase that specifically cleaves the conserved N-glycan on IgG antibodies. In vitro, removal of this glycan impairs IgG effector functions, but its relevance to GAS infection in vivo is unclear. Using targeted mass spectrometry, we characterized the effects of EndoS on host IgG glycosylation during the course of infections in humans. Substantial IgG glycan hydrolysis occurred at the site of infection and systemically in the severe cases. We demonstrated decreased resistance to phagocytic killing of GAS lacking EndoS in vitro and decreased virulence in a mouse model of invasive infection. This is the first described example of specific bacterial IgG glycan hydrolysis during infection and thereby verifies the hypothesis that EndoS modifies antibodies in vivo. This mechanisms of immune evasion could have implications for treatment of severe GAS infections and for future efforts at vaccine development.

scholarly journals Survey of the bp/tee genes from clinical group A streptococcus isolates in New Zealand – implications for vaccine development

2014 ◽  
Vol 63 (12) ◽  
pp. 1670-1678 ◽  
Author(s):  
John D. Steemson ◽  
Nicole J. Moreland ◽  
Deborah Williamson ◽  
Julie Morgan ◽  
Philip E. Carter ◽  
...  
Keyword(s):  
New Zealand ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Invasive Disease ◽  
T Antigen ◽  
Clinical Group ◽  
Wide Range ◽  
Life Threatening ◽  
Group A ◽  
The Individual

Group A streptococcus (GAS) is responsible for a wide range of diseases ranging from superficial infections, such as pharyngitis and impetigo, to life-threatening diseases, such as toxic shock syndrome and acute rheumatic fever (ARF). GAS pili are hair-like extensions protruding from the cell surface and consist of highly immunogenic structural proteins: the backbone pilin (BP) and one or two accessory pilins (AP1 and AP2). The protease-resistant BP builds the pilus shaft and has been recognized as the T-antigen, which forms the basis of a major serological typing scheme that is often used as a supplement to M typing. A previous sequence analysis of the bp gene (tee gene) in 39 GAS isolates revealed 15 different bp/tee types. In this study, we sequenced the bp/tee gene from 100 GAS isolates obtained from patients with pharyngitis, ARF or invasive disease in New Zealand. We found 20 new bp/tee alleles and four new bp/tee types/subtypes. No association between bp/tee type and clinical outcome was observed. We confirmed earlier reports that the emm type and tee type are associated strongly, but we also found exceptions, where multiple tee types could be found in certain M/emm type strains, such as M/emm89. We also reported, for the first time, the existence of a chimeric bp/tee allele, which was assigned into a new subclade (bp/tee3.1). A strong sequence conservation of the bp/tee gene was observed within the individual bp/tee types/subtypes (>97 % sequence identity), as well as between historical and contemporary New Zealand and international GAS strains. This temporal and geographical sequence stability provided further evidence for the potential use of the BP/T-antigen as a vaccine target.

scholarly journals Dextromethorphan Efficiently Increases Bactericidal Activity, Attenuates Inflammatory Responses, and Prevents Group A Streptococcal Sepsis

2011 ◽  
Vol 55 (3) ◽  
pp. 967-973 ◽  
Author(s):  
Ming-Han Li ◽  
Yueh-Hsia Luo ◽  
Chiou-Feng Lin ◽  
Yu-Tzu Chang ◽  
Shiou-Ling Lu ◽  
...  
Keyword(s):  
Bactericidal Activity ◽  
Inflammatory Responses ◽  
Group A Streptococcus ◽  
Wide Spectrum ◽  
Serum Levels ◽  
Streptococcal Toxic Shock Syndrome ◽  
Necrosis Factor Alpha ◽  
Bacterial Killing ◽  
Air Pouch ◽  
Group A

ABSTRACTGroup A streptococcus (GAS) is an important human pathogen that causes a wide spectrum of diseases, ranging from mild throat and skin infections to severe invasive diseases such as necrotizing fasciitis and streptococcal toxic shock syndrome. Dextromethorphan (DM), a dextrorotatory morphinan and a widely used antitussive drug, has recently been reported to possess anti-inflammatory properties. In this study, we investigated the potential protective effect of DM in GAS infection using an air pouch infection mouse model. Our results showed that DM treatment increased the survival rate of GAS-infected mice. Bacterial numbers in the air pouch were lower in mice treated with DM than in those infected with GAS alone. The bacterial elimination efficacy was associated with increased cell viability and bactericidal activity of air-pouch-infiltrating cells. Moreover, DM treatment prevented bacterial dissemination in the blood and reduced serum levels of the proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-1β and the chemokines monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 2 (MIP-2), and RANTES. In addition, GAS-induced mouse liver injury was reduced by DM treatment. Taken together, DM can increase bacterial killing and reduce inflammatory responses to prevent sepsis in GAS infection. The consideration of DM as an adjunct treatment in combination with antibiotics against bacterial infection warrants further study.

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