摘要

细菌发病机制的关键组成部分是入侵有机体感知和适应宿主免疫系统强加的恶劣环境的能力。这对机会性病原体尤为重要，例如鲍曼不动杆菌，这是一种营养多样性的环境有机体，最近受到人们的关注，成为威胁生命的人类病原体。鲍曼不动杆菌的出现与抗生素耐药性密切相关，许多当代分离株均为耐多药（MDR）。与许多其他MDR病原体不同，鲍曼不动杆菌发病机制的分子机制在很大程度上仍不清楚。我们在这里报告了两个最近确定的毒力决定簇GigA和GigB的特征，它们包含了存活的环境压力所需的信号转导途径，引起感染和抗生素抗性。通过转录组分析，我们显示GigA和GigB协调地调节许多基因的表达，并且是在抗生素暴露期间产生适当的转录反应所需的。遗传和生物化学数据表明GigA和GigB以及氮磷酸转移酶系统（PTSNtr）之间的直接联系，建立了新型应激反应模块与良好保守的代谢传感通路之间的新型连接。根据这里提供的结果，我们建议GigA和GigB是A. baumannii全球应激反应的主要监管者，并且将该途径与PTSNtr耦合允许A.baumannii将细胞代谢状态与外部环境线索整合。

A critical component of bacterial pathogenesis is the ability of an invading organism to sense and adapt to the harsh environment imposed by the host's immune system. This is especially important for opportunistic pathogens, such asAcinetobacter baumannii, a nutritionally versatile environmental organism that has recently gained attention as a life-threatening human pathogen. The emergence ofA. baumannii is closely linked to antibiotic resistance, and many contemporary isolates are multidrug resistant (MDR). Unlike many other MDR pathogens, the molecular mechanisms underlying A. baumannii pathogenesis remain largely unknown. We report here the characterization of two recently identified virulence determinants, GigA and GigB, which comprise a signal transduction pathway required for surviving environmental stresses, causing infection and antibiotic resistance. Through transcriptome analysis, we show that GigA and GigB coordinately regulate the expression of many genes and are required for generating an appropriate transcriptional response during antibiotic exposure. Genetic and biochemical data demonstrate a direct link between GigA and GigB and the nitrogen phosphotransferase system (PTSNtr), establishing a novel connection between a novel stress response module and a well-conserved metabolic-sensing pathway. Based on the results presented here, we propose that GigA and GigB are master regulators of a global stress response in A. baumannii, and coupling this pathway with the PTSNtr allows A. baumannii to integrate cellular metabolic status with external environmental cues.

http://jb.asm.org/content/199/10/e00066-17.short