Environmental and genetic regulation of the phosphorylcholine epitope of Haemophilus influenzae lipooligosaccharide.
Environmental and genetic regulation of the phosphorylcholine epitope of Haemophilus influenzae lipooligosaccharide.
复制标题
流感嗜血杆菌脂寡糖磷酸胆碱表位的环境和遗传调控。
DOI：
10.1111/j.1365-2958.2004.04439.x
复制
发表时间：
2005
影响因子：
3.6
通讯作者：
Akerley,BrianJ
中科院分区：
文献类型：
--
作者：
Wong,SandyM;Akerley,BrianJ
为了响应宿主的环境信号，细菌病原体表达感染期间所需的因子，并抑制那些干扰该过程特定阶段的因子。控制人类呼吸道病原体流感嗜血杆菌毒力因子的信号通路主要是未知的。脂寡糖（LOS）外核代表了流感嗜血杆菌的典型毒力性状，它不仅增强了毒力，而且还为先天性和适应性免疫提供了靶点。 我们报告了LOS上毒力相关磷酸胆碱（PC）表位在环境条件下的表达调控。PC显示在微好氧条件下是最佳的，在高培养通气条件下显着降低。进行使用DNA微阵列的基因表达分析，以开始确定在这些条件下细胞的代谢状态，并鉴定潜在参与PC表位调节的基因。全球基因表达谱检测氧化还原反应基因和碳水化合物代谢基因的变化。对碳水化合物代谢的影响使我们研究了csrA的假定流感嗜血杆菌同源物的作用，csrA是大肠杆菌糖酵解和大肠杆菌异生的调节剂。 含有流感嗜血杆菌csrA基因框内缺失的突变体在需氧条件下显示PC表位水平增加。 此外，csrA的缺失提高了galU的mRNA表达，galU是一种必需的毒力基因，在产生多糖形成和LOS外核合成所需的糖前体中至关重要。预测改变培养物的氧化还原状态的生长条件也调节PC表位和galU表达。结果与控制LOS-PC表位显示的多因素机制一致，涉及csrA和环境信号，协调调节控制LOS结构的生物合成和代谢基因。
In response to environmental signals in the host, bacterial pathogens express factors required during infection and repress those that interfere with specific stages of this process. Signalling pathways controlling virulence factors of the human respiratory pathogen,Haemophilus influenzae,are predominantly unknown. The lipooligosaccharide (LOS) outer core represents a prototypical virulence trait ofH. influenzaethat enhances virulence but also provides targets for innate and adaptive immunity. We report regulation of the display of the virulence‐associated phosphorylcholine (PC) epitope on the LOS in response to environmental conditions. PC display is optimal under microaerobic conditions and markedly decreased under conditions of high culture aeration. Gene expression analysis using a DNA microarray was performed to begin to define the metabolic state of the cell under these conditions and to identify genes potentially involved in PC epitope modulation. Global gene expression profiling detected changes in redox responsive genes and in genes of carbohydrate metabolism. The effects on carbohydrate metabolism led us to examine the role of the putativeH. influenzaehomologue ofcsrA, a regulator of glycolysis and gluconeogenesis inEscherichia coli. A mutant containing an in‐frame deletion of theH. influenzae csrAgene showed increased PC epitope levels under aerobic conditions. Furthermore, deletion ofcsrAelevated mRNA expression ofgalU, an essential virulence gene that is critical in generating sugar precursors needed for polysaccharide formation and LOS outer core synthesis. Growth conditions predicted to alter the redox state of the culture modulated the PC epitope andgalUexpression as well. The results are consistent with a multifactorial mechanism of control of LOS‐PC epitope display involvingcsrAand environmental signals that coordinately regulate biosynthetic and metabolic genes controlling the LOS structure.