Disease manifestations and pathogenic mechanisms of Group A Streptococcus
Mark J Walker1, Timothy C Barnett, Jason D McArthur
1School of Chemistry and Molecular Biosciences and the Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD, Australia.
Abstract:
Streptococcus pyogenes, also known as group A Streptococcus (GAS), causes mild human infections such as pharyngitis and impetigo and serious infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, repeated GAS infections may trigger autoimmune diseases, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease. Combined, these diseases account for over half a million deaths per year globally. Genomic and molecular analyses have now characterized a large number of GAS virulence determinants, many of which exhibit overlap and redundancy in the processes of adhesion and colonization, innate immune resistance, and the capacity to facilitate tissue barrier degradation and spread within the human host. This improved understanding of the contribution of individual virulence determinants to the disease process has led to the formulation of models of GAS disease progression, which may lead to better treatment and intervention strategies. While GAS remains sensitive to all penicillins and cephalosporins, rising resistance to other antibiotics used in disease treatment is an increasing worldwide concern. Several GAS vaccine formulations that elicit protective immunity in animal models have shown promise in nonhuman primate and early-stage human trials. The development of a safe and efficacious commercial human vaccine for the prophylaxis of GAS disease remains a high priority.
Insights
Group A Streptococcus (GAS) causes various infections and autoimmune diseases, leading to over 500,000 deaths annually. Research into GAS virulence factors and vaccine development is crucial for effective treatment and prevention strategies.
Area of Science:
- Microbiology
- Infectious Diseases
- Immunology
Background:
- Streptococcus pyogenes, or group A Streptococcus (GAS), is responsible for a spectrum of human illnesses, ranging from mild pharyngitis to life-threatening conditions like necrotizing fasciitis and toxic shock syndrome.
- Repeated GAS infections can precipitate autoimmune disorders, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease, contributing to over 500,000 global deaths annually.
Purpose of the Study:
- To analyze the virulence determinants of GAS and their roles in disease pathogenesis.
- To explore potential therapeutic and preventative strategies, including vaccine development, against GAS infections.
Main Methods:
- Genomic and molecular analyses were employed to characterize GAS virulence factors.
- Disease progression models were formulated based on the understanding of these determinants.
- Preclinical and early-stage human trials of GAS vaccine candidates were reviewed.
Main Results:
- GAS virulence determinants exhibit overlap and redundancy in adhesion, colonization, immune evasion, and tissue degradation.
- Understanding these factors aids in modeling GAS disease progression.
- While GAS remains sensitive to penicillins, antibiotic resistance to other agents is a growing concern.
Conclusions:
- Improved knowledge of GAS virulence factors facilitates the development of novel treatment and intervention strategies.
- Promising GAS vaccine candidates have emerged from preclinical and early-stage human trials.
- Developing a safe and effective commercial human vaccine for GAS prophylaxis is a high priority.
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