Burkholderia type VI secretion systems have distinct roles in eukaryotic and bacterial cell interactions.

Burkholderia type VI secretion systems have distinct roles in eukaryotic and bacterial cell interactions.
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DOI:
10.1371/journal.ppat.1001068
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发表时间:
2010-08-26
期刊:
影响因子:
6.7
通讯作者:
Mougous JD
Mougous JD
中科院分区:
医学1区
文献类型:
--
作者:
Schwarz S;West TE;Boyer F;Chiang WC;Carl MA;Hood RD;Rohmer L;Tolker-Nielsen T;Skerrett SJ;Mougous JD

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生活在环境中的细菌已经进化出专门防御真核生物或其他细菌的途径。在这篇论文中,我们系统地研究了泰国伯克霍尔德氏菌的五个VI型分泌系统(T6SS)在真核细胞和细菌细胞相互作用中的作用。与将泰国巴氏杆菌T6SS与特征良好的细菌和真核细胞靶向T6SS的分布进行比较的系统发育分析一致,我们发现T6SS-5在小鼠类鼻疽模型中对生物体的毒力起着关键作用,而缺乏其他四个T6SS的菌株仍然与野生型一样毒力。T6SS-5的功能似乎是宿主特有的,与体内生长缺陷无关,因为ΔT6SS-5在缺乏MyD88的小鼠中是完全毒力的。接下来,我们探讨了这五个系统在细菌间相互作用中的作用。从一组31种不同的细菌中,我们发现了几种与缺乏T6SS-1功能的菌株相比,对野生型泰国杆菌的竞争效率较低的几种微生物。T6SS-1的失活使泰国芽孢杆菌更容易受到恶臭假单胞菌、荧光假单胞菌和变形沙雷氏菌的细胞接触诱导的停滞-使其在与这些微生物的竞争实验中比野生菌株的适合度低100-1000倍。流动细胞生物膜分析表明,T6S依赖的细菌间相互作用可能与环境有关。缺乏T6SS-1的泰国细胞在恶臭假单胞菌的混合生物膜中迅速被置换,而野生型细胞持续存在并超过竞争对手。我们的数据表明,单个生物体内的T6SS在真核细胞与细菌细胞的相互作用中可以具有不同的功能。这些系统很可能是一个物种细菌细胞存活的决定性因素,与另一个物种的细菌细胞密切相关,例如在环境中和许多感染中都存在的多菌群落中。许多细菌都会遇到真核细胞和其他细菌物种,这是它们生活方式的一部分。为了竞争和生存,这些细菌进化出了针对这些不同类型细胞的专门途径。VI型分泌系统(T6SS)是一种细菌蛋白输出机器,被认为是使用与噬菌体结构相似的设备刺穿目标细胞。我们研究了泰兰伯克霍尔德氏菌的5个T6SS在防御其他细菌和高等生物中的作用。泰兰假单胞菌是一种相对无毒的土壤腐生菌,与人类病原菌假单胞菌关系密切。我们的工作发现了两个泰兰巴氏杆菌T6SS的作用,它们在机体在小鼠宿主中的生存或对抗另一种细菌细胞中具有特殊的功能。我们还发现,缺乏细菌靶向T6SS的泰兰杆菌不能在与竞争细菌的混合生物膜中生存。根据T6SS的进化关系,以及我们的发现,泰兰巴氏杆菌以T6S依赖的方式与其他细菌物种接触,我们推测这一途径对多菌人类疾病和环境中的细菌间相互作用具有普遍意义。
Bacteria that live in the environment have evolved pathways specialized to defend against eukaryotic organisms or other bacteria. In this manuscript, we systematically examined the role of the five type VI secretion systems (T6SSs) of Burkholderia thailandensis (B. thai) in eukaryotic and bacterial cell interactions. Consistent with phylogenetic analyses comparing the distribution of the B. thai T6SSs with well-characterized bacterial and eukaryotic cell-targeting T6SSs, we found that T6SS-5 plays a critical role in the virulence of the organism in a murine melioidosis model, while a strain lacking the other four T6SSs remained as virulent as the wild-type. The function of T6SS-5 appeared to be specialized to the host and not related to an in vivo growth defect, as ΔT6SS-5 was fully virulent in mice lacking MyD88. Next we probed the role of the five systems in interbacterial interactions. From a group of 31 diverse bacteria, we identified several organisms that competed less effectively against wild-type B. thai than a strain lacking T6SS-1 function. Inactivation of T6SS-1 renders B. thai greatly more susceptible to cell contact-induced stasis by Pseudomonas putida, Pseudomonas fluorescens and Serratia proteamaculans—leaving it 100- to 1000-fold less fit than the wild-type in competition experiments with these organisms. Flow cell biofilm assays showed that T6S-dependent interbacterial interactions are likely relevant in the environment. B. thai cells lacking T6SS-1 were rapidly displaced in mixed biofilms with P. putida, whereas wild-type cells persisted and overran the competitor. Our data show that T6SSs within a single organism can have distinct functions in eukaryotic versus bacterial cell interactions. These systems are likely to be a decisive factor in the survival of bacterial cells of one species in intimate association with those of another, such as in polymicrobial communities present both in the environment and in many infections. Many bacteria encounter both eukaryotic cells and other bacterial species as a part of their lifestyles. In order to compete and survive, these bacteria have evolved specialized pathways that target these distinct cell types. Type VI secretion systems (T6SSs) are bacterial protein export machines postulated to puncture targeted cells using an apparatus that shares structural similarity to bacteriophage. We investigated the role of the five T6SSs of Burkholderia thailandensis in the defense of the organism against other bacteria and higher organisms. B. thailandensis is a relatively avirulent soil saprophyte that is closely related to the human pathogen B. pseudomallei. Our work uncovered roles for two B. thailandensis T6SSs with specialized functions either in the survival of the organism in a murine host, or against another bacterial cell. We also found that B. thailandensis lacking the bacterial-targeting T6SS could not persist in a mixed biofilm with a competing bacterium. Based on the evolutionary relationship of T6SSs, and our findings that B. thailandensis engages other bacterial species in a T6S-dependent manner, we speculate that this pathway is of general significance to interbacterial interactions in polymicrobial human diseases and the environment.
DOI: 10.1099/00207713-48-1-317
发表时间: 1998-01-01
期刊: INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY
影响因子: --
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Brett, PJ;DeShazer, D;Woods, DE
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