The Importance of the Group A<i>Streptococcus</i>Capsule in the Pathogenesis of Human Infections: A Historical Perspective

Stollerman, Gene H.; Dale, James B.

doi:10.1086/529194

Cited by 71 publications

(54 citation statements)

References 72 publications

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“…Our findings clearly illustrate a model of GAS evolution in which invasive strains originate from all major lineages of strains causing pharyngitis. Invasive strains are genetically more similar to the population of pharyngitis strains from which they evolved rather than other invasive strains as a whole, confirming, on a genome level, observations that during epidemics of invasive disease, circulating pharyngitis strains frequently share morphological characteristics found in invasive strains (16,24). Further, we did not identify any single highly prevalent genetic variant that would explain the differences in disease phenotype between pharyngitis and invasive strains.…”

Section: Resultssupporting

confidence: 84%

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Distinct signatures of diversifying selection revealed by genome analysis of respiratory tract and invasive bacterial populations

Shea¹,

Beres²,

Flores

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Many pathogens colonize different anatomical sites, but the selective pressures contributing to survival in the diverse niches are poorly understood. Group A Streptococcus (GAS) is a humanadapted bacterium that causes a range of infections. Much effort has been expended to dissect the molecular basis of invasive (sterilesite) infections, but little is known about the genomes of strains causing pharyngitis (streptococcal "sore throat"). Additionally, there is essentially nothing known about the genetic relationships between populations of invasive and pharyngitis strains. In particular, it is unclear if invasive strains represent a distinct genetic subpopulation of strains that cause pharyngitis. We compared the genomes of 86 serotype M3 GAS pharyngitis strains with those of 215 invasive M3 strains from the same geographical location. The pharyngitis and invasive groups were highly related to each other and had virtually identical phylogenetic structures, indicating they belong to the same genetic pool. Despite the overall high degree of genetic similarity, we discovered that strains from different host environments (i.e., throat, normally sterile sites) have distinct patterns of diversifying selection at the nucleotide level. In particular, the pattern of polymorphisms in the hyaluronic acid capsule synthesis operon was especially different between the two strain populations. This finding was mirrored by data obtained from fullgenome analysis of strains sequentially cultured from nonhuman primates. Our results answer the long-standing question of the genetic relationship between GAS pharyngitis and invasive strains. The data provide previously undescribed information about the evolutionary history of pathogenic microbes that cause disease in different anatomical sites.genomics | infectious disease | microevolution | pathogenomics | population genetics

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Section: Resultssupporting

confidence: 84%

“…During epidemics of invasive infection, GAS strains are often highly encapsulated and have increased virulence in animal models (14)(15)(16). This increased virulence of mucoid strains can be significantly attenuated by disruption of genes in the has operon (17,18).…”

Section: Resultsmentioning

confidence: 99%

Distinct signatures of diversifying selection revealed by genome analysis of respiratory tract and invasive bacterial populations

Shea¹,

Beres²,

Flores

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Capsule expression is upregulated in human blood (190,191), and hyperencapsulated (mucoid) strains are frequently isolated from patients with GAS invasive disease (192). Encoded by the highly conserved hasABC synthase operon (193,194), the capsule is a high-molec- ular-mass polymer of glucuronic ␤-1,3-N-acetylglucosamine (195) and is structurally identical to the hyaluronic acid expressed on human cell surfaces and connective tissue, allowing GAS to subvert the host immune response through molecular mimicry (6).…”

Section: Resistance To Opsonophagocytosismentioning

confidence: 99%

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

et al. 2014

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SUMMARY 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.

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“…In gram-positive bacteria, UDP-D-glucose is the substrate for the glycosylation of teichoic acids and for biosynthesis of the glycolipid diglucosyldialcylglycerol (Glc2-DAG), the membrane anchor of lipoteichoic acids (Chassaing and Auvray, 2007). UDP-Dglucose is also an important sugar precursor for the biosynthesis of hyaluronic acid (HA) by streptococci, being the encapsulation of these bacteria by HA considered an important virulence factor (Stollerman and Dale, 2008). HA is a linear polymer of the repeating disaccharide composed of glucuronic acid (GlcA) and N-acetyl-glucosamine (GlcNAc) (Stollerman and Dale, 2008).…”

Section: Udp-d-glucosementioning

confidence: 99%

“…UDP-Dglucose is also an important sugar precursor for the biosynthesis of hyaluronic acid (HA) by streptococci, being the encapsulation of these bacteria by HA considered an important virulence factor (Stollerman and Dale, 2008). HA is a linear polymer of the repeating disaccharide composed of glucuronic acid (GlcA) and N-acetyl-glucosamine (GlcNAc) (Stollerman and Dale, 2008). UDP-D-glucose is the precursor for the synthesis of GlcA.…”

Section: Udp-d-glucosementioning

confidence: 99%

Activated Sugar Precursors: Biosynthetic Pathways and Biological Roles of an Important Class of Intermediate Metabolites in Bacteria

Sousa¹,

Feliciano²,

Leitão³

2011

Biotechnology of Biopolymers

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The Importance of the Group AStreptococcusCapsule in the Pathogenesis of Human Infections: A Historical Perspective

Cited by 71 publications

References 72 publications

Distinct signatures of diversifying selection revealed by genome analysis of respiratory tract and invasive bacterial populations

Distinct signatures of diversifying selection revealed by genome analysis of respiratory tract and invasive bacterial populations

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

Activated Sugar Precursors: Biosynthetic Pathways and Biological Roles of an Important Class of Intermediate Metabolites in Bacteria

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