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Group A Streptococcus Gene Expression in Humans and Cynomolgus Macaques with Acute Pharyngitis

机译：人和食蟹猕猴急性咽炎的A组链球菌基因表达

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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.
机译：A组链球菌（GAS）在宿主粘膜表面存活并引起急性咽炎的分子机制了解甚少。为了提供有关GAS宿主-病原体相互作用的新信息，我们使用了实时逆转录PCR（RT-PCR）分析了18例小儿咽炎患者的咽拭子样本中17种GAS基因的转录本。研究了已知和推定的毒力基因和调控基因（包括七个两组分调控系统中的基因）的表达。与组成型表达的控制基因 proS 相比，几种已知的，以前未鉴定的GAS毒力基因调节剂得到了高度表达。为了在受控条件下检查体内基因转录，将三只食蟹猕猴感染了MGAS5005菌株，该菌株在基因上代表了从北美和西欧从咽炎和侵袭性疾病发作中回收的大多数血清型M1菌株。这三只动物出现了GAS咽炎的临床体征和症状，并血清转化为多种GAS细胞外蛋白。在整个12天的感染方案中定期收集的咽拭子材料的实时RT-PCR分析表明，GAS基因子集的表达谱准确地反映了在人类儿科患者中观察到的谱。我们的研究结果表明，体内GAS基因表达的分析在从受感染的人类和非人类灵长类动物获得的咽拭子样本中是可行的。此外，我们得出结论，食蟹猕猴是一种有用的非人类灵长类动物模型，用于研究由GAS引起的急性咽炎的分子事件。

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