Complete Genome Sequencing and Comparative Phenotypic Analysis Reveal the Discrepancy Between Clostridioides difficile ST81 and ST37 Isolates.

Complete Genome Sequencing and Comparative Phenotypic Analysis Reveal the Discrepancy Between Clostridioides difficile ST81 and ST37 Isolates.
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完整的基因组测序和比较表型分析揭示了艰难梭菌 ST81 和 ST37 分离株之间的差异

DOI:
10.3389/fmicb.2021.776892
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发表时间:
2021
影响因子:
5.2
通讯作者:
Peng Y
Peng Y
中科院分区:
生物学2区
文献类型:
--
作者:
Su T;Chen W;Wang D;Cui Y;Ni Q;Jiang C;Dong D;Peng Y

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毒素 A 阴性、毒素 B 阳性的艰难梭菌菌株(主要包括 ST81 和 ST37 基因型)在中国导致抗生素相关性腹泻的艰难梭菌感染中占主导地位。最近,ST81 被报道为最流行的基因型,而不是 ST37,尽管这两种基因型的遗传和功能特征仍然不明确。在本研究中,我们通过完整的基因组测序和表型分析对这两种基因型进行了全面的比较分析。全基因组测序显示,ST81和ST37分离株遗传相关性密切,基因组成相似,核心基因组共享率较高。 ST81 中鉴定的整合和共轭元件与 ST37 中的相似,尽管具有更多的多样性和插入区域。通过表征与宿主中定植或存活相关的表型,我们发现ST81分离株在体外和体内均表现出强大的定植能力和存活能力,孢子产量增强,运动性略有增加,这可能归因于相关功能基因中非同义单核苷酸多态性的差异。此外,与 ST37 分离株相比,ST81 分离株对氟喹诺酮类药物的耐药率显着较高(94.12% vs. 62.5%),且大多携带 GyrB 中的氨基酸取代 Asp426Val。总之,我们的研究结果表明,ST81 分离株表现出增强的在宿主之间传播和在恶劣环境中生存的能力,为进一步的流行病学调查和艰难梭菌感染监测提供了关键的遗传见解。
Toxin A-negative, toxin B-positive Clostridioides difficile strains, which primarily include the ST81 and ST37 genotypes, are predominant in C. difficile infections leading to antibiotic-associated diarrhea in China. Recently, ST81 has been reported as the most prevalent genotype rather than ST37, although the genetic and functional characteristics of the two genotypes remain ambiguous. In this study, we conducted comprehensive comparative analysis of these two genotypes through complete genome sequencing and phenotypic profiling. The whole genome sequencing revealed that the ST81 and ST37 isolates were closely related genetically with similar gene compositions, and high rate of the core genome shared. The integrative and conjugative elements identified in ST81 were similar to those in ST37, albeit with more diverse and insertion regions. By characterizing the phenotypes related to colonization or survival in the host, we found that the ST81 isolates exhibited robust colonization ability and survival both in vitro and in vivo, enhanced spore production, and slightly increased motility, which may be attributable to the discrepancy in non-synonymous single-nucleotide polymorphisms in the relevant functional genes. Furthermore, the ST81 isolates displayed a significantly higher rate of resistance to fluoroquinolones compared with the ST37 isolates (94.12% vs. 62.5%) and mostly carried the amino acid substitution Asp426Val in GyrB. In summary, the results of our study indicate that ST81 isolates exhibit enhanced ability to transmit between hosts and survive in harsh environments, providing key genetic insights for further epidemiological investigations and surveillance of C. difficile infection.
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