Characterisation of emergent toxigenic M1 UK Streptococcus pyogenes and associated sublineages
Characterisation of emergent toxigenic M1 UK Streptococcus pyogenes and associated sublineages
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新兴产毒 M1 UK 化脓性链球菌及相关亚系的特征
DOI：
10.1101/2022.12.27.522030
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Li H
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文献类型：
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作者：
Li H
化脓性链球菌基因型emm 1是一个成功的，全球分布的流行性克隆，被认为是固有的毒性。产生SpeA毒素水平增加的Anemm 1亚系M1 UK与2015/2016年英格兰猩红热和侵袭性感染的增加有关。由核心基因组中的27个SNP定义，M1 UK现在在英格兰占主导地位。为了更全面地表征M1 UK，我们对M1 UK和当代非M1 UKemm 1菌株（M1 global）进行了比较转录组学和蛋白质组学分析。与同时代的M1 globalstrains相比，M1 UK只有7个基因表达差异。除了speA，操纵子中包括甘油脱氢酶的5个基因在M1 UK中上调（gldA、mipB/talC、pflD和磷酸转移酶系统IIC和IIB组分），而水通道蛋白（glpF 2）下调。M1 UK株有一个终止密码子ldA。缺失gldA在M1 global废除甘油脱氢酶活性，并重演上调基因表达的操纵子，包括gldA，与反馈效应一致。系统发育分析确定了英格兰的两个中间emm 1亚系，分别包含13/27（M113 SNPs）和23/27（M123 SNPs），它们未能在人群中扩展。蛋白质组学分析的侵袭性菌株从四个hepatogeneticemm 1组突出了亚系特定的变化，碳水化合物代谢，蛋白质合成和蛋白质加工;上调SpeA中未观察到化学成分确定的培养基。然而，在丰富的肉汤中，SpeA的表达在M123 SNP和M1 UK亚系中均上调约10倍，与M113 SNP和M1 global相比。我们的结论是，逐步积累的SNPs导致M1 UK的出现。虽然SpeA表达的增加是M1 UK的关键指标，并且无疑是重要的，但M1 UK菌株已经胜过了M123 SNP和产生类似或更多超抗原毒素的其他类型。我们推测，自适应SNPs的积累，有助于更广泛的健身优势，在M1 UKon一个固有的successfulemm 1链球菌背景。
Streptococcus pyogenesgenotypeemm1 is a successful, globally distributed epidemic clone that is regarded as inherently virulent. Anemm1 sublineage, M1UK, that produces increased levels of SpeA toxin was associated with increased scarlet fever and invasive infections in England in 2015/2016. Defined by 27 SNPs in the core genome, M1UKis now dominant in England. To more fully characterize M1UK, we undertook comparative transcriptomic and proteomic analyses of M1UKand contemporary non-M1UKemm1 strains (M1global). Just seven genes were differentially expressed by M1UKcompared with contemporary M1globalstrains. In addition tospeA, five genes in the operon that includes glycerol dehydrogenase were upregulated in M1UK(gldA, mipB/talC, pflD, and phosphotransferase system IIC and IIB components), while aquaporin (glpF2) was downregulated. M1UKstrains have a stop codon ingldA. Deletion ofgldAin M1globalabrogated glycerol dehydrogenase activity, and recapitulated upregulation of gene expression within the operon that includesgldA, consistent with a feedback effect. Phylogenetic analysis identified two intermediateemm1 sublineages in England comprising 13/27 (M113SNPs) and 23/27 SNPs (M123SNPs), respectively, that had failed to expand in the population. Proteomic analysis of invasive strains from the four phylogeneticemm1 groups highlighted sublineage-specific changes in carbohydrate metabolism, protein synthesis and protein processing; upregulation of SpeA was not observed in chemically defined medium. In rich broth, however, expression of SpeA was upregulated ~10-fold in both M123SNPsand M1UKsublineages, compared with M113SNPsand M1global. We conclude that stepwise accumulation of SNPs led to the emergence of M1UK. While increased expression of SpeA is a key indicator of M1UKand undoubtedly important, M1UKstrains have outcompeted M123SNPsand otheremmtypes that produce similar or more superantigen toxin. We speculate that an accumulation of adaptive SNPs has contributed to a wider fitness advantage in M1UKon an inherently successfulemm1 streptococcal background.