Identification of a Novel Small Non-Coding RNA Modulating the Intracellular Survival of Brucella melitensis.
Identification of a Novel Small Non-Coding RNA Modulating the Intracellular Survival of Brucella melitensis.
复制标题
鉴定调节布鲁氏菌细胞内存活的新型小非编码 RNA。
DOI：
10.3389/fmicb.2015.00164
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发表时间：
2015
影响因子：
5.2
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Wang Y;Ke Y;Xu J;Wang L;Wang T;Liang H;Zhang W;Gong C;Yuan J;Zhuang Y;An C;Lei S;Du X;Wang Z;Li W;Yuan X;Huang L;Yang X;Chen Z
细菌小非编码rna （sRNAs）是对环境变化、应激条件和发病机制作出反应的基因表达调节剂。本研究采用生物信息学和实验相结合的方法，在细胞内病原菌布鲁氏菌中鉴定了8个新的sRNA基因。BSR0602是一个在固定期被高度诱导的sRNA，进一步研究发现它可以调节B. melitensis的细胞内存活。BSR0602在体外应激下的水平非常高，与宿主巨噬细胞感染过程中遇到的应激相似。此外，BSR0602在感染小鼠的脾脏中高表达，提示其可能在控制发病机制中发挥作用。BSR0602靶向编码gntR的mrna， gntR是一种全局转录调节因子，是山羊白杆菌毒力所必需的。BSR0602过表达导致gntR mRNA水平明显降低。高水平BSR0602的B. melitensis在巨噬细胞内存活缺陷，在感染小鼠的脾脏中生长缺陷。因此，BSR0602可能直接抑制gntR的表达，从而损害布鲁氏菌的细胞内存活，导致布鲁氏菌感染。我们的研究结果表明BSR0602负责细菌对应激条件的适应，从而调节B. melitensis的细胞内存活。
Bacterial small non-coding RNAs (sRNAs) are gene expression modulators respond to environmental changes, stressful conditions, and pathogenesis. In this study, by using a combined bioinformatic and experimental approach, eight novel sRNA genes were identified in intracellular pathogen Brucella melitensis. BSR0602, one sRNA that was highly induced in stationary phase, was further examined and found to modulate the intracellular survival of B. melitensis. BSR0602 was present at very high levels in vitro under stresses similar to those encountered during infection in host macrophages. Furthermore, BSR0602 was found to be highly expressed in the spleens of infected mice, suggesting its potential role in the control of pathogenesis. BSR0602 targets the mRNAs coding for gntR, a global transcriptional regulator, which is required for B. melitensis virulence. Overexpression of BSR0602 results in distinct reduction in the gntR mRNA level. B. melitensis with high level of BSR0602 is defective in bacteria intracellular survival in macrophages and defective in growth in the spleens of infected mice. Therefore, BSR0602 may directly inhibit the expression of gntR, which then impairs Brucellae intracellular survival and contributes to Brucella infection. Our findings suggest that BSR0602 is responsible for bacterial adaptation to stress conditions and thus modulate B. melitensis intracellular survival.