Human Immune Response to Streptococcal Inhibitor of Complement, a Serotype M1 Group A<i>Streptococcus</i>Extracellular Protein Involved in Epidemics

Hoe, Nancy P.; Kordari, Parichher; Cole, Robert L.; Liu, Mengyao; Palzkill, Timothy; Huang, Wanzhi; McLellan, Duncan; Adams, Gerald J.; Hu, Mary C.; Vuopio‐Varkila, Jaana; Cate, Thomas R.; Pichichero, Michael E.; Edwards, Kathryn M.; Eskola, Juhani; Low, Donald E.; Musser, James M.

doi:10.1086/315882

Cited by 42 publications

(46 citation statements)

References 41 publications

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“…To gain new insight into GAS gene expression in vivo in human patients with acute pharyngitis, we measured relative transcript levels of 17 genes in throat swab specimens by quantitative TaqMan real-time RT-PCR. Analysis of transcript levels of several genes encoding known and putative extracellular virulence factors was consistent with serological evidence that these GAS genes are expressed during infection (6,21,42,43). For example, SpeB, Mac, and BspA have been shown to be synthesized in vivo in infected humans, as judged by analysis of antibody levels present in acute-and convalescent-phase sera (27,34,42,43).…”

Section: Discussionsupporting

confidence: 62%

Group AStreptococcusGene Expression in Humans and Cynomolgus Macaques with Acute Pharyngitis

Virtaneva¹,

Graham²,

Porcella³

et al. 2003

Infect Immun

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The molecular mechanisms used by group A Streptococcus (GAS) to survive on the host mucosal surface and cause acute pharyngitis are poorly understood. To provide new information about GAS host-pathogen interactions, we used real-time reverse transcription-PCR (RT-PCR) to analyze transcripts of 17 GAS genes in throat swab specimens taken from 18 pediatric patients with pharyngitis. The expression of known and putative virulence genes and regulatory genes (including genes in seven two-component regulatory systems) was studied. Several known and previously uncharacterized GAS virulence gene regulators were highly expressed compared to the constitutively expressed control gene proS. To examine in vivo gene transcription in a controlled setting, three cynomolgus macaques were infected with strain MGAS5005, an organism that is genetically representative of most serotype M1 strains recovered from pharyngitis and invasive disease episodes in North America and Western Europe. These three animals developed clinical signs and symptoms of GAS pharyngitis and seroconverted to several GAS extracellular proteins. Real-time RT-PCR analysis of throat swab material collected at intervals throughout a 12-day infection protocol indicated that expression profiles of a subset of GAS genes accurately reflected the profiles observed in the human pediatric patients. The results of our study demonstrate that analysis of in vivo GAS gene expression is feasible in throat swab specimens obtained from infected human and nonhuman primates. In addition, we conclude that the cynomolgus macaque is a useful nonhuman primate model for the study of molecular events contributing to acute pharyngitis caused by GAS.

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Section: Discussionsupporting

confidence: 62%

Group AStreptococcusGene Expression in Humans and Cynomolgus Macaques with Acute Pharyngitis

Virtaneva¹,

Graham²,

Porcella³

et al. 2003

Infect Immun

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“…The peptides were received dried and were reconstituted with 200 l of 99.9% dimethyl sulfoxide (Sigma, St. Louis, Mo.). The reactivity of the peptides with rabbit anti-Mac 5005 or rabbit anti-Mac 8345 diluted 1:20,000 was analyzed as described previously (10).…”

Section: Methodsmentioning

confidence: 99%

Opsonophagocytosis-Inhibiting Mac Protein of Group A Streptococcus : Identification and Characteristics of Two Genetic Complexes

et al. 2002

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). To study mac variation and expression of the Mac protein, the gene in 67 GAS strains representing 36 distinct M protein serotypes was sequenced. Two distinct genetic complexes were identified, and they were designated complex I and complex II. Mac variants in each of the two complexes were closely related, but complex I and complex II variants differed on average at 50.66 ؎ 5.8 amino acid residues, most of which were located in the middle one-third of the protein. Taken together, the data add to the emerging theme in GAS pathogenesis that allelic variation in virulence genes contributes to fundamental differences in host-pathogen interactions among strains.

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“…Overlapping 15 mers, corresponding to regions of variation in Emm3.1 and Emm3.2, also were used. Analysis of the reactivity of sera from rabbits immunized with synthetic peptides M3.1 and M3.2 was done in 96-well streptavidin-coated plates (30).…”

Section: Analysis Of Variation In the Gene (Sclb) Encoding Streptococcalmentioning

confidence: 99%

Genome-wide molecular dissection of serotype M3 group A Streptococcus strains causing two epidemics of invasive infections

Beres

Sylva

Sturdevant

et al. 2004

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

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121

115

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Molecular factors that contribute to the emergence of new virulent bacterial subclones and epidemics are poorly understood. We hypothesized that analysis of a population-based strain sample of serotype M3 group A Streptococcus (GAS) recovered from patients with invasive infection by using genome-wide investigative methods would provide new insight into this fundamental infectious disease problem. Serotype M3 GAS strains (n ‫؍‬ 255) cultured from patients in Ontario, Canada, over 11 years and representing two distinct infection peaks were studied. Genetic diversity was indexed by pulsed-field gel electrophoresis, DNA-DNA microarray, whole-genome PCR scanning, prophage genotyping, targeted gene sequencing, and single-nucleotide polymorphism genotyping. All variation in gene content was attributable to acquisition or loss of prophages, a molecular process that generated unique combinations of proven or putative virulence genes. Distinct serotype M3 genotypes experienced rapid population expansion and caused infections that differed significantly in character and severity. Molecular genetic analysis, combined with immunologic studies, implicated a 4-aa duplication in the extreme N terminus of M protein as a factor contributing to an epidemic wave of serotype M3 invasive infections. This finding has implications for GAS vaccine research. Genome-wide analysis of population-based strain samples cultured from clinically well defined patients is crucial for understanding the molecular events underlying bacterial epidemics.population genetics ͉ evolution ͉ phage ͉ subclone

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Human Immune Response to Streptococcal Inhibitor of Complement, a Serotype M1 Group AStreptococcusExtracellular Protein Involved in Epidemics

Cited by 42 publications

References 41 publications

Group AStreptococcusGene Expression in Humans and Cynomolgus Macaques with Acute Pharyngitis

Group AStreptococcusGene Expression in Humans and Cynomolgus Macaques with Acute Pharyngitis

Opsonophagocytosis-Inhibiting Mac Protein of Group A Streptococcus : Identification and Characteristics of Two Genetic Complexes

Genome-wide molecular dissection of serotype M3 group A Streptococcus strains causing two epidemics of invasive infections

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