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1.
六型分泌系统(type VI secretion system, T6SS)作为一种广泛存在于革兰氏阴性细菌中的可收缩纳米装置,通过将有毒物质,即效应因子(effector)注射于真核或原核细胞体内,杀死真核捕食者或原核竞争对手.近年来,T6SS基因的多样性、纳米装置的组装和效应因子的致病机制等都获得了广泛关注,取得了重大的突破.本综述基于T6SS的基因组成、组件装配、效应因子种类和调节机制等,分析总结T6SS基因组成的多样性,不同元件组装机制和对应的结构基础,效应因子种类和致病机理,以及T6SS复杂的调控网络等方面的研究进展和未解决的问题,以期为T6SS的研究提供参考. 相似文献
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Secretion systems are essential for bacteria to survive and manipulate their environment. The bacterial type VI secretion system (T6SS) generates the force needed for protein translocation by the contraction of a long polymer called sheath. The sheath is a six‐start helical assembly of interconnected VipA/VipB subunits. The mechanism of T6SS sheath contraction is unknown. Here, we show that elongating the N‐terminal VipA linker or eliminating charge of a specific VipB residue abolishes sheath contraction and delivery of effectors into target cells. Mass spectrometry analysis identified the inner tube protein Hcp, spike protein VgrG, and other components of the T6SS baseplate significantly enriched in samples of the stable non‐contractile sheaths. The ability to lock the T6SS in the pre‐firing state opens new possibilities for understanding its mode of action. 相似文献
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Chimeric adaptor proteins translocate diverse type VI secretion system effectors in Vibrio cholerae
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Daniel Unterweger Benjamin Kostiuk Rina Ötjengerdes Ashley Wilton Laura Diaz‐Satizabal Stefan Pukatzki 《The EMBO journal》2015,34(16):2198-2210
Vibrio cholerae is a diverse species of Gram-negative bacteria, commonly found in the aquatic environment and the causative agent of the potentially deadly disease cholera. These bacteria employ a type VI secretion system (T6SS) when they encounter prokaryotic and eukaryotic competitors. This contractile puncturing device translocates a set of effector proteins into neighboring cells. Translocated effectors are toxic unless the targeted cell produces immunity proteins that bind and deactivate incoming effectors. Comparison of multiple V. cholerae strains indicates that effectors are encoded in T6SS effector modules on mobile genetic elements. We identified a diverse group of chimeric T6SS adaptor proteins required for the translocation of diverse effectors encoded in modules. An example for a T6SS effector that requires T6SS adaptor protein 1 (Tap-1) is TseL found in pandemic V. cholerae O1 serogroup strains and other clinical isolates. We propose a model in which Tap-1 is required for loading TseL onto the secretion apparatus. After T6SS-mediated TseL export is completed, Tap-1 is retained in the bacterial cell to load other T6SS machines. 相似文献
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A phospholipase A1 antibacterial Type VI secretion effector interacts directly with the C‐terminal domain of the VgrG spike protein for delivery
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Nicolas Flaugnatti Thi Thu Hang Le Stéphane Canaan Marie‐Stéphanie Aschtgen Van Son Nguyen Stéphanie Blangy Christine Kellenberger Alain Roussel Christian Cambillau Eric Cascales Laure Journet 《Molecular microbiology》2016,99(6):1099-1118
The Type VI secretion system (T6SS) is a multiprotein machine that delivers protein effectors in both prokaryotic and eukaryotic cells, allowing interbacterial competition and virulence. The mechanism of action of the T6SS requires the contraction of a sheath‐like structure that propels a needle towards target cells, allowing the delivery of protein effectors. Here, we provide evidence that the entero‐aggregative Escherichia coli Sci‐1 T6SS is required to eliminate competitor bacteria. We further identify Tle1, a toxin effector encoded by this cluster and showed that Tle1 possesses phospholipase A1 and A2 activities required for the interbacterial competition. Self‐protection of the attacker cell is secured by an outer membrane lipoprotein, Tli1, which binds Tle1 in a 1:1 stoichiometric ratio with nanomolar affinity, and inhibits its phospholipase activity. Tle1 is delivered into the periplasm of the prey cells using the VgrG1 needle spike protein as carrier. Further analyses demonstrate that the C‐terminal extension domain of VgrG1, including a transthyretin‐like domain, is responsible for the interaction with Tle1 and its subsequent delivery into target cells. Based on these results, we propose an additional mechanism of transport of T6SS effectors in which cognate effectors are selected by specific motifs located at the C‐terminus of VgrG proteins. 相似文献
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Badreddine Douzi Laureen Logger Silvia Spinelli Stéphanie Blangy Christian Cambillau Eric Cascales 《Journal of molecular biology》2018,430(3):297-309
The type VI secretion system (T6SS) is a specialized macromolecular complex dedicated to the delivery of protein effectors into both eukaryotic and bacterial cells. The general mechanism of action of the T6SS is similar to the injection of DNA by contractile bacteriophages. The cytoplasmic portion of the T6SS is evolutionarily, structurally and functionally related to the phage tail complex. It is composed of an inner tube made of stacked Hcp hexameric rings, engulfed within a sheath and built on a baseplate. This sheath undergoes cycles of extension and contraction, and the current model proposes that the sheath contraction propels the inner tube toward the target cell for effector delivery. The sheath comprises two subunits: TssB and TssC that polymerize under an extended conformation. Here, we show that isolated TssB forms trimers, and we report the crystal structure of a C-terminal fragment of TssB. This fragment comprises a long helix followed by a helical hairpin that presents surface-exposed charged residues. Site-directed mutagenesis coupled to functional assay further showed that these charges are required for proper assembly of the sheath. Positioning of these residues in the extended T6SS sheath structure suggests that they may mediate contacts with the baseplate. 相似文献
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Type VI secretion system MIX‐effectors carry both antibacterial and anti‐eukaryotic activities
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Ann Ray Nika Schwartz Marcela de Souza Santos Junmei Zhang Kim Orth Dor Salomon 《EMBO reports》2017,18(11):1978-1990
Most type VI secretion systems (T6SSs) described to date are protein delivery apparatuses that mediate bactericidal activities. Several T6SSs were also reported to mediate virulence activities, although only few anti‐eukaryotic effectors have been described. Here, we identify three T6SSs in the marine bacterium Vibrio proteolyticus and show that T6SS1 mediates bactericidal activities under warm marine‐like conditions. Using comparative proteomics, we find nine potential T6SS1 effectors, five of which belong to the polymorphic MIX‐effector class. Remarkably, in addition to six predicted bactericidal effectors, the T6SS1 secretome includes three putative anti‐eukaryotic effectors. One of these is a MIX‐effector containing a cytotoxic necrotizing factor 1 domain. We demonstrate that T6SS1 can use this MIX‐effector to target phagocytic cells, resulting in morphological changes and actin cytoskeleton rearrangements. In conclusion, the V. proteolyticus T6SS1, a system homologous to one found in pathogenic vibrios, uses a suite of polymorphic effectors that target both bacteria and eukaryotic neighbors. 相似文献
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The Type VI secretion system (T6SS) is a widespread macromolecular structure that delivers protein effectors to both eukaryotic and prokaryotic recipient cells. The current model describes the T6SS as an inverted phage tail composed of a sheath‐like structure wrapped around a tube assembled by stacked Hcp hexamers. Although recent progress has been made to understand T6SS sheath assembly and dynamics, there is no evidence that Hcp forms tubes in vivo. Here we show that Hcp interacts with TssB, a component of the T6SS sheath. Using a cysteine substitution approach, we demonstrate that Hcp hexamers assemble tubes in an ordered manner with a head‐to‐tail stacking that are used as a scaffold for polymerization of the TssB/C sheath‐like structure. Finally, we show that VgrG but not TssB/C controls the proper assembly of the Hcp tubular structure. These results highlight the conservation in the assembly mechanisms between the T6SS and the bacteriophage tail tube/sheath. 相似文献
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Novel T3SS effector EseK in Edwardsiella piscicida is chaperoned by EscH and EscS to express virulence
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Huifang Cao Cuiting Yang Shu Quan Tianjian Hu Lingzhi Zhang Yuanxing Zhang Dahai Yang Qin Liu 《Cellular microbiology》2018,20(1)
Bacterium usually utilises type III secretion systems (T3SS) to deliver effectors directly into host cells with the aids of chaperones. Hence, it is very important to identify bacterial T3SS effectors and chaperones for better understanding of host–pathogen interactions. Edwardsiella piscicida is an invasive enteric bacterium, which infects a wide range of hosts from fish to human. Given E. piscicida encodes a functional T3SS to promote infection, very few T3SS effectors and chaperones have been identified in this bacterium so far. Here, we reported that EseK is a new T3SS effector protein translocated by E. piscicida. Bioinformatic analysis indicated that escH and escS encode two putative class I T3SS chaperones. Further investigation indicated that EscH and EscS can enhance the secretion and translocation of EseK. EscH directly binds EseK through undetermined binding domains, whereas EscS binds EseK via its N‐terminal α‐helix. We also found that EseK has an N‐terminal chaperone‐binding domain, which binds EscH and EscS to form a ternary complex. Zebrafish infection experiments showed that EseK and its chaperones EscH and EscS are necessary for bacterial colonisation in zebrafish. This work identified a new T3SS effector, EseK, and its two T3SS chaperones, EscH and EscS, in E. piscicida, which enriches our knowledge of bacterial T3SS effector–chaperone interaction and contributes to our understanding of bacterial pathogenesis. 相似文献
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Dor Salomon John A. Klimko David C. Trudgian Lisa N. Kinch Nick V. Grishin Hamid Mirzaei Kim Orth 《PLoS pathogens》2015,11(8)
The type VI secretion system (T6SS) is a widespread protein secretion apparatus used by Gram-negative bacteria to deliver toxic effector proteins into adjacent bacterial or host cells. Here, we uncovered a role in interbacterial competition for the two T6SSs encoded by the marine pathogen Vibrio alginolyticus. Using comparative proteomics and genetics, we identified their effector repertoires. In addition to the previously described effector V12G01_02265, we identified three new effectors secreted by T6SS1, indicating that the T6SS1 secretes at least four antibacterial effectors, of which three are members of the MIX-effector class. We also showed that the T6SS2 secretes at least three antibacterial effectors. Our findings revealed that many MIX-effectors belonging to clan V are “orphan” effectors that neighbor mobile elements and are shared between marine bacteria via horizontal gene transfer. We demonstrated that a MIX V-effector from V. alginolyticus is a functional T6SS effector when ectopically expressed in another Vibrio species. We propose that mobile MIX V-effectors serve as an environmental reservoir of T6SS effectors that are shared and used to diversify antibacterial toxin repertoires in marine bacteria, resulting in enhanced competitive fitness. 相似文献
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Christopher J. Alteri Stephanie D. Himpsl Shannon R. Pickens Jonathon R. Lindner Jonathan S. Zora Jessa E. Miller Peter D. Arno Samuel W. Straight Harry L. T. Mobley 《PLoS pathogens》2013,9(9)
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. 相似文献
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The bacterial type VI secretion system (T6SS) is used by donor cells to inject toxic effectors into receptor cells. The donor cells produce the corresponding immunity proteins to protect themselves against the effector proteins, thereby preventing their self-intoxication. Recently, the C-terminal domain of VgrG3 was identified as a T6SS effector. Information on the molecular mechanism of VgrG3 and its immunity protein TsaB has been lacking. Here, we determined the crystal structures of native TsaB and the VgrG3C–TsaB complex. VgrG3C adopts a canonical phage-T4-lysozyme-like fold. TsaB interacts with VgrG3C through molecular mimicry, and inserts into the VgrG3C pocket. 相似文献
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Abdelrahim Zoued Jean-Pierre Duneau Eric Durand Alexandre P. España Laure Journet Françoise Guerlesquin Eric Cascales 《Journal of molecular biology》2018,430(7):987-1003
The type VI secretion system (T6SS) is a multiprotein complex used by bacteria to deliver effectors into target cells. The T6SS comprises a bacteriophage-like contractile tail structure anchored to the cell envelope by a membrane complex constituted of the TssJ outer-membrane lipoprotein and the TssL and TssM inner-membrane proteins. TssJ establishes contact with the periplasmic domain of TssM whereas the transmembrane segments of TssM and its cytoplasmic domain interact with TssL. TssL protrudes in the cytoplasm but is anchored by a C-terminal transmembrane helix (TMH). Here, we show that TssL TMH dimerization is required for the stability of the protein and for T6SS function. Using the TOXCAT assay and point mutations of the 23 residues of the TssL TMH, we identified Thr194 and Trp199 as necessary for TssL TMH dimerization. NMR hydrogen–deuterium exchange experiments demonstrated the existence of a dimer with the presence of Trp185 and Trp199 at the interface. A structural model based on molecular dynamic simulations shows that TssL TMH dimer formation involves π–π interactions resulting from the packing of the two Trp199 rings at the C-terminus and of the six aromatic rings of Tyr184, Trp185 and Trp188 at the N-terminus of the TMH. 相似文献
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Jun Li Yufeng Yao H. Howard Xu Limin Hao Zixin Deng Kumar Rajakumar Hong‐Yu Ou 《Environmental microbiology》2015,17(7):2196-2202
SecReT6 ( http://db‐mml.sjtu.edu.cn/SecReT6/ ) is an integrated database providing comprehensive information on type VI secretion systems (T6SSs) in bacteria. T6SSs are a class of sophisticated cell contact‐dependent apparatuses involved in mediating antagonistic or synergistic communications between bacteria and/or bacteria and eukaryotes. These apparatuses have recently been found to be widely distributed among Gram‐negative bacterial species. SecReT6 offers a unique, readily explorable archive of known and putative T6SSs, and cognate effectors found in bacteria. It currently contains data on 11 167 core T6SS components mapping to 906 T6SSs found in 498 bacterial strains representing 240 species, as well as a collection of over 600 directly relevant references. Also collated and archived were 1340 diverse candidate secreted effectors which were experimentally shown and/or predicted to be delivered by T6SSs into target eukaryotic and/or prokaryotic cells as well as 196 immunity proteins. A broad range of T6SS gene cluster detection and comparative analysis tools are readily accessible via SecReT6, which may aid identification of effectors and immunity proteins around the T6SS core components. This database will be regularly updated to ensure its ongoing maximal utility and relevance to the scientific research community. 相似文献
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副溶血弧菌Ⅲ型分泌系统(T3SS)效应蛋白及其对宿主细胞的操控 总被引:1,自引:0,他引:1
副溶血弧菌是典型的食源性病原菌,也是全球范围内引起肠胃炎的主要病原菌。针筒状的Ⅲ型分泌系统(T3SS)为该菌主要的毒力因子,细菌感染时可将其效应蛋白直接注射至宿主细胞中,通过效应蛋白操纵宿主细胞,介导毒力的发挥。多数临床分离的副溶血弧菌含有2套T3SSs,其中T3SS1分泌的效应蛋白主要通过诱导细胞自噬、变圆和裂解等过程来发挥其细胞毒性,而T3SS2分泌的效应蛋白则主要通过破坏细胞骨架和操控细胞信号传导来发挥肠毒性。本文主要对副溶血弧菌T3SSs的组成和目前已发现的效应蛋白及其对宿主细胞的操控进行介绍。该研究不仅对深入了解该菌的致病机制有重要意义,而且也为宿主细胞信号转导机制研究提供新视角。 相似文献
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Yvann Bourigault Charly A. Dupont Jonas B. Desjardins Thierry Doan Mathilde Bouteiller Hugo Le Guenno Sylvie Chevalier Corinne Barbey Xavier Latour Eric Cascales Annabelle Merieau 《Environmental microbiology》2023,25(11):2564-2579
The type VI secretion system (T6SS) is a contractile nanomachine widespread in Gram-negative bacteria. The T6SS injects effectors into target cells including eukaryotic hosts and competitor microbial cells and thus participates in pathogenesis and intermicrobial competition. Pseudomonas fluorescens MFE01 possesses a single T6SS gene cluster that confers biocontrol properties by protecting potato tubers against the phytopathogen Pectobacterium atrosepticum (Pca). Here, we demonstrate that a functional T6SS is essential to protect potato tuber by reducing the pectobacteria population. Fluorescence microscopy experiments showed that MFE01 displays an aggressive behaviour with an offensive T6SS characterized by continuous and intense T6SS firing activity. Interestingly, we observed that T6SS firing is correlated with rounding of Pectobacterium cells, suggesting delivery of a potent cell wall targeting effector. Mutagenesis coupled with functional assays then revealed that a putative T6SS secreted amidase, Tae3Pf, is mainly responsible for MFE01 toxicity towards Pca. Further studies finally demonstrated that Tae3Pf is toxic when produced in the periplasm, and that its toxicity is counteracted by the Tai3Pf inner membrane immunity protein. 相似文献
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Regulation of Vibrio parahaemolyticus T3SS2 gene expression and function of T3SS2 effectors that modulate actin cytoskeleton
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Toshio Kodama Hirotaka Hiyoshi Ryu Okada Shigeaki Matsuda Kazuyoshi Gotoh Tetsuya Iida 《Cellular microbiology》2015,17(2):183-190
Vibrio parahaemolyticus is a leading causative agent of seafood‐borne gastroenteritis worldwide. Most clinical isolates from patients with diarrhoea possess two sets of genes for the type III secretion system (T3SS) on each chromosome (T3SS1 and T3SS2). T3SS is a protein secretion system that delivers effector proteins directly into eukaryotic cells. The injected effectors modify the normal cell functions by altering or disrupting the normal cell signalling pathways. Of the two sets of T3SS genes present in V. parahaemolyticus, T3SS2 is essential for enterotoxicity in several animal models. Recent studies have elucidated the biological activities of several T3SS2 effectors and their roles in virulence. This review focuses on the regulation of T3SS2 gene expression and T3SS2 effectors that specifically target the actin cytoskeleton. 相似文献