The Global Transcription Factor Lrp Controls Virulence Modulation in Xenorhabdus nematophila
The Global Transcription Factor Lrp Controls Virulence Modulation in Xenorhabdus nematophila
复制标题
DOI：
10.1128/jb.00272-15
复制
发表时间：
2015-09-01
影响因子：
3.2
通讯作者：
Goodrich-Blair, Heidi
中科院分区：
文献类型：
--
作者：
Hussa, Elizabeth A.;Casanova-Torres, Angel M.;Goodrich-Blair, Heidi
细菌嗜黄杆菌在对昆虫幼虫的致病性方面参与表型变异，从同基因培养物产生毒性和减毒的细胞亚群。全局调节蛋白Lrp是X.在昆虫中的嗜蚜蝇毒力和免疫抑制，以及共生宿主线虫Steinernema carpocapsae的定殖，并介导涉及这些表型中的每一个的许多基因的表达。考虑到Lrp在X.嗜热宿主协会，以及其参与调节其他细菌的表型变异途径，我们评估了其在毒力调制的功能。我们发现lrp的表达在同基因群体中是不同的，其表达方式与毒力的调节相关。出乎意料的是，尽管Lrp是最佳毒力和免疫抑制所必需的，但表达高水平Lrp的细胞在这些过程中相对于具有低至中等Lrp表达的那些细胞被减弱。此外，固定表达lrp在高和低水平分别导致减弱和正常的毒力和免疫抑制，并消除这些表型的群体变异性。这些数据表明，波动的lrp表达水平足以驱动X的表型变异。重要的是，许多细菌利用细胞间的表型变异来科普环境变化，其特征在于在同基因群体中具有不同的表型亚群。病原菌利用这种策略来改变抗原或毒力因子的表达。我们的工作确定，全球转录因子Lrp调节昆虫病原体嗜黄杆菌的表型变异，导致昆虫宿主的毒力和免疫抑制的衰减。出乎意料的是，我们发现Lrp表达水平和毒力之间的负相关性：高水平的Lrp依赖性推定的毒力基因的表达是有害的毒力，但可能有一个适应性的优势，在其他方面的生活周期。X.的研究嗜水气单胞菌的表型变异有助于在自然共生的背景下解剖这种现象。
The bacterium Xenorhabdus nematophila engages in phenotypic variation with respect to pathogenicity against insect larvae, yielding both virulent and attenuated subpopulations of cells from an isogenic culture. The global regulatory protein Lrp is necessary for X. nematophila virulence and immunosuppression in insects, as well as colonization of the mutualistic host nematode Steinernema carpocapsae, and mediates expression of numerous genes implicated in each of these phenotypes. Given the central role of Lrp in X. nematophila host associations, as well as its involvement in regulating phenotypic variation pathways in other bacteria, we assessed its function in virulence modulation. We discovered that expression of lrp varies within an isogenic population, in a manner that correlates with modulation of virulence. Unexpectedly, although Lrp is necessary for optimal virulence and immunosuppression, cells expressing high levels of lrp were attenuated in these processes relative to those with low to intermediate lrp expression. Furthermore, fixed expression of lrp at high and low levels resulted in attenuated and normal virulence and immunosuppression, respectively, and eliminated population variability of these phenotypes. These data suggest that fluctuating lrp expression levels are sufficient to drive phenotypic variation in X. nematophila.IMPORTANCEMany bacteria use cell-to-cell phenotypic variation, characterized by distinct phenotypic subpopulations within an isogenic population, to cope with environmental change. Pathogenic bacteria utilize this strategy to vary antigen or virulence factor expression. Our work establishes that the global transcription factor Lrp regulates phenotypic variation in the insect pathogen Xenorhabdus nematophila, leading to attenuation of virulence and immunosuppression in insect hosts. Unexpectedly, we found an inverse correlation between Lrp expression levels and virulence: high levels of expression of Lrp-dependent putative virulence genes are detrimental for virulence but may have an adaptive advantage in other aspects of the life cycle. Investigation of X. nematophila phenotypic variation facilitates dissection of this phenomenon in the context of a naturally occurring symbiosis.