Division of Molecular Microbiology, College of Life Sciences, University of Dundee, United Kingdom.
J Bacteriol. 2011 Nov;193(21):6057-69. doi: 10.1128/JB.05671-11. Epub 2011 Sep 2.
The type VI secretion system (T6SS) is the most recently described and least understood of the protein secretion systems of Gram-negative bacteria. It is widely distributed and has been implicated in the virulence of various pathogens, but its mechanism and exact mode of action remain to be defined. Additionally there have been several very recent reports that some T6SSs can target bacteria rather than eukaryotic cells. Serratia marcescens is an opportunistic enteric pathogen, a class of bacteria responsible for a significant proportion of hospital-acquired infections. We describe the identification of a functional T6SS in S. marcescens strain Db10, the first report of type VI secretion by an opportunist enteric bacterium. The T6SS of S. marcescens Db10 is active, with secretion of Hcp to the culture medium readily detected, and is expressed constitutively under normal growth conditions from a large transcriptional unit. Expression of the T6SS genes did not appear to be dependent on the integrity of the T6SS. The S. marcescens Db10 T6SS is not required for virulence in three nonmammalian virulence models. It does, however, exhibit dramatic antibacterial killing activity against several other bacterial species and is required for S. marcescens to persist in a mixed culture with another opportunist pathogen, Enterobacter cloacae. Importantly, this antibacterial killing activity is highly strain specific, with the S. marcescens Db10 T6SS being highly effective against another strain of S. marcescens with a very similar and active T6SS. We conclude that type VI secretion plays a crucial role in the competitiveness, and thus indirectly the virulence, of S. marcescens and other opportunistic bacterial pathogens.
VI 型分泌系统(T6SS)是革兰氏阴性菌中最近描述的、了解最少的蛋白分泌系统。它广泛分布,并与各种病原体的毒力有关,但它的机制和确切作用方式仍有待确定。此外,最近有几项报告表明,一些 T6SS 可以靶向细菌而不是真核细胞。粘质沙雷氏菌是一种机会性肠道病原体,是一类负责相当一部分医院获得性感染的细菌。我们描述了功能 T6SS 在 Db10 菌株中的鉴定,这是首次报道机会性肠道细菌具有类型 VI 分泌。Db10 菌株的 T6SS 是活跃的,很容易检测到 Hcp 分泌到培养基中,并且在正常生长条件下从一个大的转录单元组成型表达。T6SS 基因的表达似乎不依赖于 T6SS 的完整性。Db10 菌株的 T6SS 对三种非哺乳动物毒力模型的毒力不是必需的。然而,它对几种其他细菌物种具有显著的杀菌活性,并且是 Db10 菌株在与另一种机会性病原体阴沟肠杆菌混合培养中持续存在所必需的。重要的是,这种杀菌活性具有高度的菌株特异性,Db10 菌株的 T6SS 对另一种具有非常相似和活跃的 T6SS 的粘质沙雷氏菌菌株具有高度有效性。我们得出结论,类型 VI 分泌在粘质沙雷氏菌和其他机会性病原体的竞争力中发挥着至关重要的作用,因此间接地发挥着毒力作用。