Background The genomic features and transmission link of circulating Group A Streptococcus (GAS) strains causing different disease types, such as pharyngitis and invasive disease, are not well understood. Methods We used whole-genome sequencing to characterize GAS isolates recovered from persons with pharyngitis and invasive disease in the Denver metropolitan area from June 2016 to April 2017. Results The GAS isolates were cultured from 236 invasive and 417 pharyngitis infections. Whole-genome sequencing identified 34 emm types. Compared with pharyngitis isolates, invasive isolates were more likely to carry the erm family genes (23% vs 7.4%, P<.001), which confer resistance to erythromycin and clindamycin (including inducible resistance), and covS gene inactivation (7% vs 0.5%, P<.001). Whole-genome sequencing identified 97 genomic clusters (433 isolates; 2–65 isolates per cluster) that consisted of genomically closely related isolates (median single-nucleotide polymorphism=3 [interquartile range, 1–4] within cluster). Thirty genomic clusters (200 isolates; 31% of all isolates) contained both pharyngitis and invasive isolates and were found in 11 emm types. Conclusions In the Denver metropolitan population, mixed disease types were commonly seen in clusters of closely related isolates, indicative of overlapping transmission networks. Antibiotic-resistance and covS inactivation was disproportionally associated with invasive disease.

中文翻译：

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2016 年 6 月至 2017 年 4 月在美国科罗拉多州引起咽炎和侵袭性疾病的 A 组链球菌的基因组特征

背景 导致不同疾病类型（如咽炎和侵袭性疾病）的循环 A 组链球菌 (GAS) 菌株的基因组特征和传播环节尚不清楚。方法 我们使用全基因组测序来表征 2016 年 6 月至 2017 年 4 月期间从丹佛市区咽炎和侵袭性疾病患者身上回收的 GAS 分离株。结果 GAS 分离株来自 236 例侵袭性和 417 例咽炎感染。全基因组测序鉴定出 34 种 emm 类型。与咽炎分离株相比，侵袭性分离株更有可能携带 erm 家族基因（23% 对 7.4%，P<.001），这些基因赋予对红霉素和克林霉素的耐药性（包括诱导耐药性），以及 covS 基因失活（7% 对 7.4%，P<.001） 0.5%，P<.001)。全基因组测序鉴定了 97 个基因组簇（433 个分离株；每个簇 2-65 个分离株），由基因组密切相关的分离株组成（簇内单核苷酸多态性中位数 = 3 [四分位间距，1-4]）。三十个基因组簇（200 个分离株；所有分离株的 31%）包含咽炎和侵入性分离株，并在 11 种 emm 类型中被发现。结论 在丹佛大都市人群中，混合疾病类型常见于密切相关的分离株群中，表明重叠的传播网络。抗生素耐药性和 covS 失活与侵袭性疾病不成比例地相关。三十个基因组簇（200 个分离株；所有分离株的 31%）包含咽炎和侵入性分离株，并在 11 种 emm 类型中被发现。结论 在丹佛大都市人群中，混合疾病类型常见于密切相关的分离株群中，表明重叠的传播网络。抗生素耐药性和 covS 失活与侵袭性疾病不成比例地相关。三十个基因组簇（200 个分离株；所有分离株的 31%）包含咽炎和侵入性分离株，并在 11 种 emm 类型中被发现。结论 在丹佛大都市人群中，混合疾病类型常见于密切相关的分离株群中，表明重叠的传播网络。抗生素耐药性和 covS 失活与侵袭性疾病不成比例地相关。