Molecular Basis of the Toxigenic Vibrio cholerae O1 Serotype Switch from Ogawa to Inaba in Haiti.

Molecular Basis of the Toxigenic Vibrio cholerae O1 Serotype Switch from Ogawa to Inaba in Haiti.
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DOI:
10.1128/spectrum.03624-22
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发表时间:
2023-02-14
影响因子:
3.7
通讯作者:
--
中科院分区:
生物学1区
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--
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O 1血清型Ogawa产毒素霍乱弧菌于2010年10月被非自愿引入海地,在流行的前5年中几乎所有分离的临床菌株都是Ogawa。2015年之前,稻叶病毒株被间歇性地鉴定出来,不同的突变导致了共同的表型。2015年,稻叶型的临床感染率开始迅速上升,稻叶型在随后的4年中取代小川型成为主要血清型。我们研究了血清型转换的分子基础,并证实所有Inaba菌株具有相同水平的wbeT基因的mRNA表达,以及霍乱弧菌Inaba分离株中截短的WbeT蛋白的相同翻译水平。wbeT基因表达水平、差异突变或WbeT蛋白的截短大小似乎都不是2015年成功的稻叶转换的原因。我们的遗传动态分析表明,海地的霍乱弧菌稻叶株直接从小川株进化而来,在小川-稻叶转换时,种群水平上的多样化选择显著增加。我们得出结论,稻叶血清型的出现是由多样化选择驱动的,独立于wbeT基因的突变模式。我们的生物动力学分析表明,海地的稻叶霍乱弧菌菌株直接从小川菌株进化而来。我们的研究结果支持了这样的假设,即在最初的小川主导的流行波后,霍乱弧菌稻叶能够成为优势菌株,这要归功于持续的多样化选择所驱动的选择优势,而与wbeT基因的突变模式无关。
Toxigenic Vibrio cholerae O1 serotype Ogawa was introduced involuntarily into Haiti in October 2010, and virtually all of the clinical strains isolated during the first 5 years of the epidemic were Ogawa. Inaba strains were identified intermittently prior to 2015, with diverse mutations resulting in a common phenotype. In 2015, the percentage of clinical infections due to the Inaba serotype began to rapidly increase, with Inaba supplanting Ogawa as the dominant serotype during the subsequent 4 years. We investigated the molecular basis of the serotype switch and confirmed that all Inaba strains had the same level of mRNA expression of the wbeT genes, as well as the same translation levels for the truncated WbeT proteins in the V. cholerae Inaba isolates. Neither wbeT gene expression levels, differential mutations, or truncation size of the WbeT proteins appeared to be responsible for the successful Inaba switch in 2015. Our phylodynamic analysis demonstrated that the V. cholerae Inaba strains in Haiti evolved directly from Ogawa strains and that a significant increase of diversifying selection at the population level occurred at the time of the Ogawa-Inaba switch. We conclude that the emergence of the Inaba serotype was driven by diversifying selection, independent of the mutational pattern in the wbeT gene. IMPORTANCE Our phylodynamic analysis demonstrated that Vibrio cholerae Inaba strains in Haiti evolved directly from Ogawa strains. Our results support the hypothesis that after an initial Ogawa-dominated epidemic wave, V. cholerae Inaba was able to become the dominant strain thanks to a selective advantage driven by ongoing diversifying selection, independently from the mutational pattern in the wbeT gene.
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