Type VI Secretion Effectors: Methodologies and Biology

Lien, Yun-Wei; Lai, Erh‐Min

doi:10.3389/fcimb.2017.00254

Cited by 99 publications

(110 citation statements)

References 106 publications

(225 reference statements)

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“…Here, using what is known from previously characterized T6SS‐dependent effectors, coupled with bioinformatic tools, we have identified additional putative T6SS‐dependent non‐TssI effectors and their cognate immunity proteins encoded by the B. cenocepacia genome. As T6SS‐dependent effector genes in other species are often located within close proximity to tssI genes (Lien & Lai, ), we used the predicted amino acid sequences of protein products encoded within close proximity to the ten intact tssI genes and one disrupted tssI gene (BCAL2503) present within the B. cenocepacia J2315 genome as queries in BLASTP searches to identify putative functional domains and homology to proteins belonging to established T6SS effector superfamilies (Appendix Figure A6). Twelve putative T6SS effectors were identified using this approach, with each of the tssI clusters in B. cenocepacia J2315 encoding at least one putative effector.…”

Section: Resultsmentioning

confidence: 99%

Burkholderia cenocepacia utilizes a type VI secretion system for bacterial competition

et al. 2019

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Burkholderia cenocepacia is an opportunistic bacterial pathogen that poses a significant threat to individuals with cystic fibrosis by provoking a strong inflammatory response within the lung. It possesses a type VI secretion system (T6SS), a secretory apparatus that can perforate the cellular membrane of other bacterial species and/or eukaryotic targets, to deliver an arsenal of effector proteins. The B. cenocepacia T6SS (T6SS‐1) has been shown to be implicated in virulence in rats and contributes toward actin rearrangements and inflammasome activation in B. cenocepacia ‐infected macrophages. Here, we present bioinformatics evidence to suggest that T6SS‐1 is the archetype T6SS in the Burkholderia genus. We show that B. cenocepacia T6SS‐1 is active under normal laboratory growth conditions and displays antibacterial activity against other Gram‐negative bacterial species. Moreover, B. cenocepacia T6SS‐1 is not required for virulence in three eukaryotic infection models. Bioinformatics analysis identified several candidate T6SS‐dependent effectors that may play a role in the antibacterial activity of B. cenocepacia T6SS‐1. We conclude that B. cenocepacia T6SS‐1 plays an important role in bacterial competition for this organism, and probably in all Burkholderia species that possess this system, thereby broadening the range of species that utilize the T6SS for this purpose.

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Section: Resultsmentioning

confidence: 99%

Burkholderia cenocepacia utilizes a type VI secretion system for bacterial competition

et al. 2019

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“…For example, an eCIS called Photorhabdus Virulence Cassettes (PVC) injects an effector causing actin condensation in insect hemocytes (Yang et al, 2006). In T6SS, a number of effectors are described that specifically target eukaryotic cells (Lien and Lai, 2017). The modes of action of these T6SS effectors include actin cross-linking in macrophages (Pukatzki et al, 2007), interaction with microtubules for invasion of epithelial cells (Sana et al, 2015), and disruption of the actin cytoskeleton of HeLa cells (Suarez et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Bacterial Phage Tail-like Structure Kills Eukaryotic Cells by Injecting a Nuclease Effector

Rocchi

Ericson

Malter

et al. 2019

Preprint

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24Many bacteria interact with target organisms using syringe-like structures called 25 Contractile Injection Systems (CIS). CIS structurally resemble headless bacteriophages 26 and share evolutionarily related proteins such as the tail tube, sheath, and baseplate 27 complex. Recent evidence shows that CIS are specialized to puncture membranes and 28 often deliver effectors to target cells. In many cases, CIS mediate trans-kingdom 29 interactions between bacteria and eukaryotes, however the effectors delivered to target 30 cells and their mode of action are often unknown. In this work, we establish an in vitro 31 model to study a CIS called Metamorphosis Associated Contractile structures (MACs) 32 that target eukaryotic cells. We show that MACs kill two eukaryotic cell lines, Fall 33Armyworm Sf9 cells and J774A.1 murine macrophage cells through the action of a 34 newly identified MAC effector, termed Pne1. To our knowledge, Pne1 is the first CIS 35 effector exhibiting nuclease activity against eukaryotic cells. Our results define a new 36 mechanism of CIS-mediated bacteria-eukaryote interaction and are a first step toward 37 understanding structures with the potential to be developed as novel delivery systems 38 for eukaryotic hosts. 39 40 63 targeting eukaryotic cells are yet described that possess nuclease activity. 64 65One group of evolutionarily related CIS have been shown to mediate interactions with 66 diverse eukaryotic organisms including amoeba, grass grubs, wax moths and wasps 67 (Böck et al., 2017; Hurst et al., 2007; Penz et al., 2012 Penz et al., , 2010 Sarris et al., 2014; Yang 68 et al., 2006). We recently described a related eCIS mediating the beneficial relationship 69 between the Gram-negative bacterium Pseudoalteramonas luteoviolacea and a marine 70 tubeworm, Hydroides elegans, hereafter Hydroides (Shikuma et al., 2014(Shikuma et al., , 2016. We 71 called this eCIS from P. luteoviolacea MACs for Metamorphosis Associated Contractile 72 structures, because they stimulate the metamorphosis of Hydroides (Shikuma et al., 73 2014). MACs are the first CIS discovered to form arrays of phage tail-like structures 74 composed of about 100 tails and often measure about 1 µm in diameter. While MACs 75 provide another example of CIS-eukaryote interactions, the range of hosts targeted by 76 eCIS like MACs as well as the identity and mode of action of effectors that mediate 77 these interactions remain poorly understood. 78 79To study the interaction between MACs and eukaryotic cells, we establish an in vitro 80 CIS-cell line interaction model with insect and mammalian cell types. Using these 81 systems, we identify a new MAC effector with nuclease activity that is responsible for 82 cytotoxicity in both cell types. Our results indicate that MACs can interact with a range 83 of host cells and a specific effector mediates killing of eukaryotic cells. 84 85 RESULTS 86 MACs kill insect cell lines in vitro. To study MACs from P. luteoviolacea and test their 87 effect on eukaryotic cells, we focused ...

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“…Contraction of the sheath enables the HCP-VgrG-PAAR protein complex to puncture the bacterial membrane and deliver various T6SS effectors into the extracellular environment or directly into the target bacterial cells 8,15,16 . The effectors can be encoded either as fused protein with the HCP/VgrG/PAAR proteins as an additional domain or they are non-covalently fused to HCP/VgrG/PAAR protein that are encoded as upstream ORF in the effector operon 12,15,17–20 . Association with HCP/VgrG/PAAR proteins/domains is essential for translocation of effectors.…”

Section: Introductionmentioning

confidence: 99%

“…Association with HCP/VgrG/PAAR proteins/domains is essential for translocation of effectors. Recent studies have suggested that certain chaperone (DUF4123, DUF1795 and DUF2169) and co-chaperones are also required for T6SS mediated delivery of effectors 20–23 . Till date, diverse kinds of proteins including phospholipases (Tli), amidases (Tae), glucosaminidase (Tge), nucleases (Rhs proteins), DNases (Tde), peptidases, pore-forming toxins etc.…”

Section: Introductionmentioning

confidence: 99%

Conversion of a defensive toxin-antitoxin system into an offensive T6SS effector in Burkholderia

Yadav

Magotra

Krishnan

et al. 2019

Preprint

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12Bacteria use various kinds of toxins to either inhibit the growth of co-habiting bacteria 13 or when needed control their own growth. Here we report that Burkholderia and 14 certain other bacteria have altered the potential defensive function of Tox-REase-5 15 domain containing toxins into offensive function. The Burkholderia gladioli strain 16 NGJ1 encodes such toxins as type VI secretion system (T6SS) effectors (Tse) and 17 potentially deploys them to kill co-habiting rice endophytic bacteria. Notably, the 18 immunity (Tsi) proteins associated with Tse effectors demonstrate functional 19 similarity with the antitoxin of type II toxin-antitoxin (TA) system. Genome analysis of 20 diverse bacteria revealed that various Tse orthologs are either encoded as TA or 21 T6SS effectors. In addition, potential evolutionary events associated with conversion 22 of TA into T6SS effectors have been delineated. Our results indicate that the 23 transposition of IS3 elements has led to the operonic fusion of certain T6SS related 24 genes with TA genes resulting in their conversion into T6SS effectors. Such a 25 genetic change has enabled bacteria to utilize novel toxins to precisely target co-26 habiting bacteria. 27 28 29Under natural conditions, bacteria have to compete with co-habiting bacteria for 30 available resources. This can lead to severe evolutionary pressure on bacteria to 31 adopt strategies to limit the growth of other cohabiting microbes 1 . Several bacterial 32 species use a specialized protein secretion system called the type VI secretion 33 system (T6SS) to target co-habiting bacteria 2-6 . The T6SS is a syringe like apparatus 34 composed of a base plate, a membrane complex (spanning the inner and outer 35 membrane) and an inner tube, being wrapped in a sheath-like structure 7-10 . 36Hexamers of the HCP (hemolysin-coregulated protein) protein forms the inner tube 37 of the T6SS apparatus 9,11 . A trimer of the VgrG (Valine-glycine repeat protein G) 38 protein forms a spike like structure on the top of the inner tube 12 . Further, the 39 PAAR (proline-alanine-alanine-arginine) repeat-containing protein binds to the 40 distal end of the spike and forms a sharp pointed tip 13,14 . Contraction of the sheath 41 enables the HCP-VgrG-PAAR protein complex to puncture the bacterial 42 membrane and deliver various T6SS effectors into the extracellular environment or 43 directly into the target bacterial cells 8,15,16 . The effectors can be encoded either as 44 fused protein with the HCP/VgrG/PAAR proteins as an additional domain or they 45 are non-covalently fused to HCP/VgrG/PAAR protein that are encoded as 46 upstream ORF in the effector operon 12,15,17-20 . Association with HCP/VgrG/PAAR 47 proteins/domains is essential for translocation of effectors. Recent studies have 48 suggested that certain chaperone (DUF4123, DUF1795 and DUF2169) and co-49 chaperones are also required for T6SS mediated delivery of effectors 20-23 . Till date, 50 diverse kinds of proteins including phospholipases (Tli), amidases (Tae), 51 gl...

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Type VI Secretion Effectors: Methodologies and Biology

Cited by 99 publications

References 106 publications

Burkholderia cenocepacia utilizes a type VI secretion system for bacterial competition

Burkholderia cenocepacia utilizes a type VI secretion system for bacterial competition

Bacterial Phage Tail-like Structure Kills Eukaryotic Cells by Injecting a Nuclease Effector

Conversion of a defensive toxin-antitoxin system into an offensive T6SS effector in Burkholderia

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