Abstract:Molecular pathogenomic analysis of the human bacterial pathogen group A Streptococcus has been conducted for a decade. Much has been learned as a consequence of the confluence of low-cost DNA sequencing, microarray technology, high-throughput proteomics, and enhanced bioinformatics. These technical advances, coupled with the availability of unique bacterial strain collections, have facilitated a systems biology investigative strategy designed to enhance and accelerate our understanding of disease processes. He… Show more
“…4,15,16,19 As more individuals are exposed to a specific serotype, that serotype becomes less fit due to the inability to transmit successfully between the decreased numbers of remaining susceptible individuals, a phenomenon known as herd immunity. [20][21][22][23] As herd immunity to a specific serotype increases, other serotypes become favored through a relative increase in transmission and hence reproduction. Because this process generally favors unique (new or recently rare) serological variants, evolutionary pressure is thought to drive the process of diversification in primary antigens and to drive cyclical turnovers in the dominance of existing serotypes.…”
Section: Protein As a Virulence Factormentioning
confidence: 99%
“…A recently emergent and virulent M3 strain experienced a small (four amino acid) duplication in the M protein itself, associated with the resurgence of this M type during an epidemic of GAS disease in 2000. 20,68 This alteration caused changes in host immune responses, suggesting significant antigenic novelty. Offering an even more striking example of the potential effects of dispersed and subtle mutations, a genome wide (mutation) association study (GWAS) offered evidence that a single nucleotide polymorphism in a metalloregulatory protein is associated with a change in the ability of GAS to cause necrotizing fasciitis, likely through alteration of the regulation of SpeB expression.…”
“…Offering an even more striking example of the potential effects of dispersed and subtle mutations, a genome wide (mutation) association study (GWAS) offered evidence that a single nucleotide polymorphism in a metalloregulatory protein is associated with a change in the ability of GAS to cause necrotizing fasciitis, likely through alteration of the regulation of SpeB expression. 20,69 Whole genome sequencing of an apparently clonal M18 strain associated with several US outbreaks of acute rheumatic fever in the 1980s and 1990s, revealed many virulence factors. 39 To offer an idea of the complexity of determining the etiological basis of differential virulence and outcomes, M18 was found to carry 178 open reading frames (most of them likely functional genes) not found in the more common serotype M1, which has been associated with sporadic cases of ARF but not the high attack rate epidemic ARF characteristic of M18.…”
“…The fluctuating dominance and precise clinical correlates of these strains are certainly affected by mutation, group B streptococci) may express this phenotype due to the acquisition of a large fragment of group B genomic sequence. 20,34,37 Host factors certainly contribute greatly to GAS virulence and clinical outcome, adding significant complexity to any effort to deconvolute the source of differential presentation. The bestcharacterized host factor is probably that of infection by Varicella Zoster Virus (VZV or human herpesvirus 3).…”
Section: O N O T D I S T R I B U T Ementioning
confidence: 99%
“…30 Differences in host response to superantigens may also play a role in severity of symptoms. 1,20 Investigation of host-specific factors led to the discovery that specific HLA alleles are involved in the development of streptococcal toxic shock syndrome 20 and ARF, 18 suggesting that direct prediction of specific case outcomes might require analysis of not only the complete genome of the infecting GAS strain, but also analysis of the host genome.…”
“…4,15,16,19 As more individuals are exposed to a specific serotype, that serotype becomes less fit due to the inability to transmit successfully between the decreased numbers of remaining susceptible individuals, a phenomenon known as herd immunity. [20][21][22][23] As herd immunity to a specific serotype increases, other serotypes become favored through a relative increase in transmission and hence reproduction. Because this process generally favors unique (new or recently rare) serological variants, evolutionary pressure is thought to drive the process of diversification in primary antigens and to drive cyclical turnovers in the dominance of existing serotypes.…”
Section: Protein As a Virulence Factormentioning
confidence: 99%
“…A recently emergent and virulent M3 strain experienced a small (four amino acid) duplication in the M protein itself, associated with the resurgence of this M type during an epidemic of GAS disease in 2000. 20,68 This alteration caused changes in host immune responses, suggesting significant antigenic novelty. Offering an even more striking example of the potential effects of dispersed and subtle mutations, a genome wide (mutation) association study (GWAS) offered evidence that a single nucleotide polymorphism in a metalloregulatory protein is associated with a change in the ability of GAS to cause necrotizing fasciitis, likely through alteration of the regulation of SpeB expression.…”
“…Offering an even more striking example of the potential effects of dispersed and subtle mutations, a genome wide (mutation) association study (GWAS) offered evidence that a single nucleotide polymorphism in a metalloregulatory protein is associated with a change in the ability of GAS to cause necrotizing fasciitis, likely through alteration of the regulation of SpeB expression. 20,69 Whole genome sequencing of an apparently clonal M18 strain associated with several US outbreaks of acute rheumatic fever in the 1980s and 1990s, revealed many virulence factors. 39 To offer an idea of the complexity of determining the etiological basis of differential virulence and outcomes, M18 was found to carry 178 open reading frames (most of them likely functional genes) not found in the more common serotype M1, which has been associated with sporadic cases of ARF but not the high attack rate epidemic ARF characteristic of M18.…”
“…The fluctuating dominance and precise clinical correlates of these strains are certainly affected by mutation, group B streptococci) may express this phenotype due to the acquisition of a large fragment of group B genomic sequence. 20,34,37 Host factors certainly contribute greatly to GAS virulence and clinical outcome, adding significant complexity to any effort to deconvolute the source of differential presentation. The bestcharacterized host factor is probably that of infection by Varicella Zoster Virus (VZV or human herpesvirus 3).…”
Section: O N O T D I S T R I B U T Ementioning
confidence: 99%
“…30 Differences in host response to superantigens may also play a role in severity of symptoms. 1,20 Investigation of host-specific factors led to the discovery that specific HLA alleles are involved in the development of streptococcal toxic shock syndrome 20 and ARF, 18 suggesting that direct prediction of specific case outcomes might require analysis of not only the complete genome of the infecting GAS strain, but also analysis of the host genome.…”
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.