Klebsiella pneumoniae is recognized as an urgent threat to human health due to the increasing isolation of multidrug resistant strains. Hypervirulent strains are a major concern due to their ability to cause life-threating infections in healthy hosts. The type VI secretion system (T6SS) is widely implicated in microbial antagonism, and it mediates interactions with host eukaryotic cells in some cases. In silico search for genes orthologous to T6SS component genes and T6SS effector genes across 700 K. pneumoniae genomes shows extensive diversity in T6SS genes across the K. pneumoniae species. Temperature, oxygen tension, pH, osmolarity, iron levels, and NaCl regulate the expression of the T6SS encoded by a hypervirulent K. pneumoniae strain. Polymyxins and human defensin 3 also increase the activity of the T6SS. A screen for regulators governing T6SS uncover the correlation between the transcription of the T6SS and the ability to kill E. coli prey. Whereas H-NS represses the T6SS, PhoPQ, PmrAB, Hfq, Fur, RpoS and RpoN positively regulate the T6SS. K. pneumoniae T6SS mediates intra and inter species bacterial competition. This antagonism is only evident when the prey possesses an active T6SS. The PhoPQ two component system governs the activation of K. pneumoniae T6SS in bacterial competitions. Mechanistically, PhoQ periplasmic domain, and the acid patch within, is essential to activate K. pneumoniae T6SS. Klebsiella T6SS also mediates anti-fungal competition. We have delineated the contribution of each of the individual VgrGs in microbial competition and identified VgrG4 as a T6SS effector. The DUF2345 domain of VgrG4 is sufficient to intoxicate bacteria and yeast. ROS generation mediates the antibacterial effects of VgrG4, and the antitoxin Sel1E protects against the toxic activity of VgrG4. Our findings provide a better understanding of the regulation of the T6SS in bacterial competitions, and place ROS as an early event in microbial competition.

肺炎克雷伯菌被认为是对人类健康的紧迫威胁，这是由于越来越多的耐多药菌株被分离出来。高毒力菌株由于其在健康宿主中引起威胁生命的感染的能力而备受关注。VI型分泌系统（T6SS）广泛参与微生物拮抗作用，并在某些情况下介​​导与宿主真核细胞的相互作用。在计算机上搜索700 K范围内与T6SS组成基因和T6SS效应子基因同源的基因。肺炎菌的基因组显示整个K上T6SS基因的广泛多样性。肺炎种类。温度，氧气张力，pH，渗透压，铁水平和NaCl调节由高毒力编码的T6SS的表达ķ。肺炎菌株。多粘菌素和人防御素3也可提高T6SS的活性。治理T6SS的调节剂的筛选揭示了T6SS的转录与杀死E的能力之间的相关性。大肠杆菌的猎物。H-NS抑制T6SS，而PhoPQ，PmrAB，Hfq，Fur，RpoS和RpoN则正调控T6SS。ķ。肺炎T6SS介导种内和种间细菌竞争。仅当猎物拥有活跃的T6SS时，这种对抗才明显。PhoPQ两组分系统控制K的激活。肺炎T6SS在细菌竞争中。从机理上讲，PhoQ周质结构域及其内部的酸斑对激活K是必不可少的。肺炎T6SS。克雷伯菌T6SS也可以介导抗真菌竞争。我们已经描述了每个单独的VgrG在微生物竞争中的贡献，并确定了VgrG4是T6SS效应子。VgrG4的DUF2345结构域足以使细菌和酵母菌陶醉。ROS的产生介导了VgrG4的抗菌作用，而抗毒素Sel1E保护了VgrG4的毒性。我们的发现提供了对细菌竞争中T6SS调控的更好理解，并将ROS列为微生物竞争中的早期事件。