Department of Life Science, National Chung-Cheng University, Chia-Yi, Taiwan.
PLoS One. 2011;6(7):e22248. doi: 10.1371/journal.pone.0022248. Epub 2011 Jul 14.
Klebsiella pneumoniae is responsible for a wide range of clinical symptoms. How this bacterium adapts itself to ever-changing host milieu is still a mystery. Recently, small non-coding RNAs (sRNAs) have received considerable attention for their functions in fine-tuning gene expression at a post-transcriptional level to promote bacterial adaptation. Here we demonstrate that Hfq, an RNA-binding protein, which facilitates interactions between sRNAs and their mRNA targets, is critical for K. pneumoniae virulence. A K. pneumoniae mutant lacking hfq (Δhfq) failed to disseminate into extra-intestinal organs and was attenuated on induction of a systemic infection in a mouse model. The absence of Hfq was associated with alteration in composition of envelope proteins, increased production of capsular polysaccharides, and decreased resistance to H(2)O(2), heat shock, and UV irradiation. Microarray-based transcriptome analyses revealed that 897 genes involved in numerous cellular processes were deregulated in the Δhfq strain. Interestingly, Hfq appeared to govern expression of many genes indirectly by affecting sigma factor RpoS and RpoE, since 19.5% (175/897) and 17.3% (155/897) of Hfq-dependent genes belong to the RpoE- and RpoS-regulon, respectively. These results indicate that Hfq regulates global gene expression at multiple levels to modulate the physiological fitness and virulence potential of K. pneumoniae.
肺炎克雷伯菌可引起多种临床症状。这种细菌如何适应宿主环境的不断变化仍然是一个谜。最近，小非编码 RNA（sRNA）因其在转录后水平精细调节基因表达以促进细菌适应的功能而受到广泛关注。在这里，我们证明 Hfq（一种 RNA 结合蛋白，可促进 sRNA 与其 mRNA 靶标之间的相互作用）对于肺炎克雷伯菌的毒力至关重要。缺乏 hfq（Δhfq）的肺炎克雷伯菌突变体无法传播到肠外器官，并且在诱导小鼠全身感染模型中减弱。缺乏 Hfq 与包膜蛋白组成的改变、荚膜多糖产量增加以及对 H2O2、热休克和 UV 照射的抵抗力降低有关。基于微阵列的转录组分析显示，Δhfq 菌株中涉及许多细胞过程的 897 个基因的表达发生了失调。有趣的是，Hfq 似乎通过影响 sigma 因子 RpoS 和 RpoE 间接调控许多基因的表达，因为 19.5%（175/897）和 17.3%（155/897）的 Hfq 依赖性基因分别属于 RpoE 和 RpoS 调控子。这些结果表明，Hfq 可在多个水平上调节全局基因表达，从而调节肺炎克雷伯菌的生理适应性和毒力潜力。
