Shotgun sequencing of Yersinia enterocolitica strain W22703 biovar 2, serovar O:9: oscillation between invertebrates and mammals. Yersinia enterocolitica strain W22703

Background: Yersinia enterocolitica strains responsible for mild gastroenteritis in humans are highly diverse with respect to their metabolic and virulence properties. Strain W22703 (biovar 2, serovar O:9) was recently identified to possess nematocidal and insecticidal activity. To better understand the relationship between pathogenicity towards insects and humans, we compared the W22703 genome with that of the highly pathogenic strain 8081 (serovar O:8, biovar 1B), the only Y. enterocolitica strain sequenced so far. Results: We used whole-genome shotgun data to assemble, annotate and analyse the sequence of strain W22703. Numerous factors assumed to contribute to enteric survival and pathogenesis, among them osmoregulated periplasmic glucan, hydrogenases, cobalamin-dependent pathways, iron uptake systems and the Yersinia genome island 1 (YGI-1) involved in tight adherence were identified to be common to the 8081 and W22703 genomes. However, sets of 551 and 550 genes revealed to be specific for W22703 and 8081 compared with the other strain. The so-called plasticity zone (PZ) of 142 kb in the W22703 genome carries an ancient flagellar cluster Flg-2 of ~40 kb, but lacks the pathogenicity island YAPIYe, the secretion system ysa and yts1, and other virulence determinants of 8081 PZ. Its composition underlines the high variability of this genome region and demonstrates its contribution to the higher pathogenicity of biovar 1B strains with respect to W22703. A novel type three secretion system (T3SS) of mosaic structure was identified in the genome of strain W22703 that is absent in the human pathogenic Yersinia species, but conserved in the genomes of the apathogenic species. Several regions of differences were identified in W22703 that mainly code for transporters, regulators, metabolic pathways, and defense factors. Conclusion: The W22703 sequence analysis revealed a genome composition distinct from other pathogenic Yersinia strains, hinting to specific environmental adaptations. This study contributes novel data to the Y. enterocolitica pan-genome and sheds further light on the strategies of this pathogen to cope with its environments.

背景：可引起人类轻度胃肠炎的小肠结肠炎耶尔森菌（Yersinia enterocolitica）菌株，其代谢与毒力特性存在高度多样性。菌株W22703（生物型2，血清型O:9）近期被证实具备杀线虫与杀虫活性。为深入解析该菌对昆虫与人类的致病性关系，本研究将W22703的基因组与高致病性菌株8081（血清型O:8，生物型1B）的基因组进行比对——菌株8081是目前已完成全基因组测序的唯一小肠结肠炎耶尔森菌菌株。

结果：本研究采用全基因组鸟枪测序（whole-genome shotgun）数据完成了菌株W22703的序列组装、注释与分析。研究鉴定出一系列与肠道存活及致病过程相关的保守因子，包括渗透压调节性周质葡聚糖、氢化酶、钴胺素依赖代谢通路、铁摄取系统，以及参与紧密黏附的耶尔森菌基因组岛1（Yersinia genome island 1, YGI-1），这些因子在8081与W22703基因组中均存在。相较彼此，W22703与8081分别拥有551个和550个特异性基因。W22703基因组中142 kb的可塑性区域（plasticity zone, PZ）携带一段约40 kb的古老鞭毛基因簇Flg-2，但缺失致病性岛YAPIYe、分泌系统ysa与yts1，以及8081 PZ中的其他毒力决定因子。该区域的组成凸显了基因组这一区域的高度变异性，并证实其与生物型1B菌株相较W22703具有更高致病性相关。本研究在W22703基因组中鉴定出一种新型嵌合结构三型分泌系统（type three secretion system, T3SS），该系统在人类致病耶尔森菌中缺失，但在非致病耶尔森菌基因组中保守存在。此外，W22703中还存在多个差异区域，其编码产物主要为转运蛋白、调控因子、代谢通路相关蛋白以及防御因子。

结论：对W22703的序列分析显示其基因组组成与其他致病性耶尔森菌菌株存在显著差异，提示其存在特定的环境适应性机制。本研究为小肠结肠炎耶尔森菌泛基因组（pan-genome）提供了全新数据，并进一步阐明了该病原体适应生存环境的策略。