Department of Clinical Laboratory, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
School of Laboratory Medicine, Hangzhou Medical College, Hangzhou, People's Republic of China.
Emerg Microbes Infect. 2021 Dec;10(1):1331-1345. doi: 10.1080/22221751.2021.1943538.
sequence type (ST) 37 (ribotype 017) is one of the most prevalent genotypes circulating in China. However, its genomic evolution and virulence determinants were rarely explored. Whole-genome sequencing, phylogeographic and phylogenetic analyses were conducted for ST37 isolates. The 325 ST37 genomes from six continents, including North America ( = 66), South America ( = 4), Oceania ( = 7), Africa ( = 9), Europe ( = 138) and Asia ( = 101), were clustered into six major lineages, with region-dependent distributions, harbouring an array of antibiotic-resistance genes. The ST37 strains from China were divided into four distinct sublineages, showing five importation times and international sources. Isolates associated with severe infections exhibited significantly higher toxin productions, mRNA levels, and sporulation capacities ( < 0.001). Kyoto Encyclopedia of Genes and Genomes analysis showed 10 metabolic pathways were significantly enriched in the mutations among isolates associated with severe CDI ( < 0.05). Gene mutations in glycometabolism, amino acid metabolism and biosynthesis virtually causing instability in protein activity were correlated positively to the transcription of and negatively to the expression of toxin repressor genes, and Y. In summary, our study firstly presented genomic insights into genetic characteristics and virulence association of ST37 in China. Gene mutations in certain important metabolic pathways are associated with severe symptoms and correlated with higher virulence in ST37 isolates.
序列型 37(核糖型 017)是在中国流行的最主要基因型之一。然而,其基因组进化和毒力决定因素很少被探索。对 ST37 分离株进行了全基因组测序、系统地理和系统发育分析。来自六大洲的 325 株 ST37 基因组,包括北美洲( = 66)、南美洲( = 4)、大洋洲( = 7)、非洲( = 9)、欧洲( = 138)和亚洲( = 101),分为六个主要谱系,具有区域依赖性分布,携带多种抗生素耐药基因。来自中国的 ST37 株分为四个不同的亚谱系,显示出五个传入时间和国际来源。与严重感染相关的分离株表现出显著更高的毒素产生、mRNA 水平和孢子形成能力( < 0.001)。京都基因与基因组百科全书分析显示,与严重 CDI 相关的分离株中存在 10 种代谢途径的突变显著富集( < 0.05)。糖代谢、氨基酸代谢和生物合成中的基因突变几乎导致蛋白质活性不稳定,与转录呈正相关,与毒素阻遏基因 、和 Y 的表达呈负相关。总之,本研究首次揭示了中国 ST37 的遗传特征和毒力相关性的基因组见解。某些重要代谢途径中的基因突变与严重症状相关,并与 ST37 分离株的更高毒力相关。