Integrated transcriptomic and proteomic analysis of the global response of Wolbachia to doxycycline-induced stress.
Integrated transcriptomic and proteomic analysis of the global response of Wolbachia to doxycycline-induced stress.
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DOI：
10.1038/ismej.2013.192
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发表时间：
2014-04
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--
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沃尔巴克氏体细菌（立克次体目），可能是世界上最丰富的垂直传播微生物，感染节肢动物和丝状线虫。在节肢动物中，沃尔巴克氏体可以诱导生殖改变并干扰几种节肢动物传播的病原体的传播。此外，沃尔巴克氏体是热带地区引起淋巴丝虫病和盘尾丝虫病的丝虫病寄生虫的专性互惠共生体。用四环素抗生素靶向沃尔巴克氏体可导致成丝虫绝育并最终死亡。然而，需要数周的治疗，限制了这一控制策略的实施。迄今为止，沃尔巴克氏体对压力的反应尚未被研究过，而且对这种有机体中基因表达的全局调控几乎一无所知。我们将一株节肢动物沃尔巴克氏菌体外暴露于多西环素中，并通过定向RNA-seq和无标记的定量蛋白质组学分析其差异表达。我们发现沃尔巴克氏体不仅通过调节翻译机制的表达做出反应，还通过上调核苷酸合成和能量代谢，同时下调外膜蛋白。此外，沃尔巴克氏体增加了双精氨酸转位酶（tatA）和磷酸ABC转运体atp酶（PstB）的关键组分的表达；后者与自由生活的细菌对抗菌剂的敏感性降低有关。最后，翻译抑制过程中6S RNA的下调表明这种小RNA参与了生长速率的控制。尽管沃尔巴克氏体的基因组高度减少，但它在暴露于强应激源时显示出令人惊讶的调节基因表达的能力。我们的发现对于专性细胞内细菌的化疗和立克次体持续存在的机制基础具有普遍的相关性。
The bacterium Wolbachia (order Rickettsiales), representing perhaps the most abundant vertically transmitted microbe worldwide, infects arthropods and filarial nematodes. In arthropods, Wolbachia can induce reproductive alterations and interfere with the transmission of several arthropod-borne pathogens. In addition, Wolbachia is an obligate mutualist of the filarial parasites that cause lymphatic filariasis and onchocerciasis in the tropics. Targeting Wolbachia with tetracycline antibiotics leads to sterilisation and ultimately death of adult filariae. However, several weeks of treatment are required, restricting the implementation of this control strategy. To date, the response of Wolbachia to stress has not been investigated, and almost nothing is known about global regulation of gene expression in this organism. We exposed an arthropod Wolbachia strain to doxycycline in vitro, and analysed differential expression by directional RNA-seq and label-free, quantitative proteomics. We found that Wolbachia responded not only by modulating expression of the translation machinery, but also by upregulating nucleotide synthesis and energy metabolism, while downregulating outer membrane proteins. Moreover, Wolbachia increased the expression of a key component of the twin-arginine translocase (tatA) and a phosphate ABC transporter ATPase (PstB); the latter is associated with decreased susceptibility to antimicrobials in free-living bacteria. Finally, the downregulation of 6S RNA during translational inhibition suggests that this small RNA is involved in growth rate control. Despite its highly reduced genome, Wolbachia shows a surprising ability to regulate gene expression during exposure to a potent stressor. Our findings have general relevance for the chemotherapy of obligate intracellular bacteria and the mechanistic basis of persistence in the Rickettsiales.
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2
作者：
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通讯作者：
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