Multicellular bacteria deploy the type VI secretion system to preemptively strike neighboring cells.

Multicellular bacteria deploy the type VI secretion system to preemptively strike neighboring cells.
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DOI:
10.1371/journal.ppat.1003608
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发表时间:
2013
期刊:
影响因子:
6.7
通讯作者:
Mobley HL
Mobley HL
中科院分区:
医学1区
文献类型:
--
作者:
Alteri CJ;Himpsl SD;Pickens SR;Lindner JR;Zora JS;Miller JE;Arno PD;Straight SW;Mobley HL

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VI 型分泌系统 (T6SS) 在细菌中充当收缩纳米机器,刺穿目标细胞并将致命效应器传递到目标细胞。事实上,我们对决定细菌何时正常产生 T6SS 的生活方式或生理学一无所知,这阻碍了我们清楚地了解细菌如何从其自然栖息地的作用中受益。奇异变形杆菌经历一个特征性的发育过程来协调多细胞集群行为,并在集群过程中将自己与另一个变形杆菌分离株区分开来,从而产生一个称为狄恩斯线的可见边界。通过转座子诱变,我们发现这种识别现象需要 T6SS 的致死作用。遗传筛选中鉴定出的所有突变体均在编码 T6SS 和同源 Hcp-VrgG 连锁效应子的单个 33.5 kb 区域内插入。通过杀伤测定、构建额外突变体、互补以及使用活细胞显微镜实时检查相对群上的 VI 型分泌系统的活性来表征鉴定的 T6SS 和初级效应操纵子。我们发现,当优势菌株深入渗透到两个群体的边界之外时,就会发生致命的 T6SS 依赖性活性。使用这种多细胞模型,我们发现细菌的社会识别、潜在杀伤和杀伤免疫都需要细胞与细胞的接触,可以分配给特定基因,并且依赖于 T6SS。在致命的 T6SS 攻击中幸存下来的能力相当于“识别”。与目前作为进攻性或防御性武器的 T6SS 模型相比,我们的研究结果支持先发制人的机制,通过该机制,整个群体在其合作增长模式期间不加区别地使用 T6SS 进行接触依赖的效应器传递。 VI 型细菌分泌系统 (T6SS) 充当收缩纳米机器,刺穿靶细胞并传递致命效应器。对于决定细菌何时正常表达 T6SS 的生活方式或生理学知之甚少。奇异变形杆菌经历了一个协调多细胞集群行为的特征性发育过程,并在集群过程中通过一条称为狄恩斯线的可见边界将自己与其他变形杆菌分离株区分开来。我们报告了这种现象,该现象于 1946 年首次被注意到,需要 T6SS、T6SS 依赖性效应器和免疫蛋白的致命作用。 T6SS 介导的致死作用对于形态上不同的群体细胞来说是独特的,并且当它发生时需要直接接触。使用这种多细胞系统,我们报告预形成的 T6SS 在细胞与细胞接触时撞击相邻细胞。我们的研究结果支持一种先发制人的机制,通过该机制,整个群体在合作行为期间不加区别地使用 T6SS,并且细菌的社会认可对致命的 T6SS 攻击具有免疫力。
The Type VI Secretion System (T6SS) functions in bacteria as a contractile nanomachine that punctures and delivers lethal effectors to a target cell. Virtually nothing is known about the lifestyle or physiology that dictates when bacteria normally produce their T6SS, which prevents a clear understanding of how bacteria benefit from its action in their natural habitat. Proteus mirabilis undergoes a characteristic developmental process to coordinate a multicellular swarming behavior and will discriminate itself from another Proteus isolate during swarming, resulting in a visible boundary termed a Dienes line. Using transposon mutagenesis, we discovered that this recognition phenomenon requires the lethal action of the T6SS. All mutants identified in the genetic screen had insertions within a single 33.5-kb region that encodes a T6SS and cognate Hcp-VrgG-linked effectors. The identified T6SS and primary effector operons were characterized by killing assays, by construction of additional mutants, by complementation, and by examining the activity of the type VI secretion system in real-time using live-cell microscopy on opposing swarms. We show that lethal T6SS-dependent activity occurs when a dominant strain infiltrates deeply beyond the boundary of the two swarms. Using this multicellular model, we found that social recognition in bacteria, underlying killing, and immunity to killing all require cell-cell contact, can be assigned to specific genes, and are dependent on the T6SS. The ability to survive a lethal T6SS attack equates to “recognition”. In contrast to the current model of T6SS being an offensive or defensive weapon our findings support a preemptive mechanism by which an entire population indiscriminately uses the T6SS for contact-dependent delivery of effectors during its cooperative mode of growth. Bacterial Type VI Secretion Systems (T6SS) function as contractile nanomachines to puncture target cells and deliver lethal effectors. Little is known about the lifestyle or physiology dictating when bacteria normally express their T6SS. Proteus mirabilis undergoes a characteristic developmental process to coordinate multicellular swarming behavior and discriminates itself from other Proteus isolates during swarming, by a visible boundary termed a Dienes line. We report this phenomenon, first noted in 1946, requires the lethal action of the T6SS, T6SS-dependent effectors, and immunity proteins. T6SS-mediated lethality is unique to morphologically distinct swarmer cells, and when it occurs requires direct contact. Using this multicellular system, we report that the pre-formed T6SS strikes neighboring cells upon cell-cell contact. Our findings support a preemptive mechanism by which an entire population indiscriminately uses the T6SS during a cooperative behavior and that social recognition in bacteria is immunity to lethal T6SS attack.
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影响因子: 11.1
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