The type 2 secretion system (often referred to as the type II secretion system or the T2SS) is protein secretion machinery found in various species of Gram-negative bacteria, including various human pathogens such as Pseudomonas aeruginosa and Vibrio cholerae. The type II secretion system is one of six protein secretory systems that are commonly found in gram negative bacteria along with the type I secretion system, the type III secretion system, The type IV secretion system, the chaperone/usher pathway, the autotransporter pathway/type V secretion system and the type VI secretion system (some bacteria also utilize the type VII secretion system). Like these other systems, the type II secretion system enables the transport of cytoplasmic proteins across the lipid bilayers that make up the cell membranes in gram negative bacteria. The type II secretion system is a membrane bound protein complex found in Gram-negative bacteria that is used to secrete proteins found in the cytoplasm of the bacteria ...
Bacterial secretion systems found in bacteria that have a MYCOLIC ACID-containing outer membrane such as MYCOBACTERIACEAE; Corynebacteriaceae; and NOCARDIACEAE. These are also known as ESX secretion systems because the first to be discovered is involved in secreting major virulence factors EsxA and EsxB. There are several subtypes of T7SSs including ESX-1, ESX-2, ESX-3, ESX-4, and ESX-5 secretion systems. The subtypes share some core components including an inner membrane channel-forming ATPase complex, a membrane-anchored mycosin, and a second channel that spans the outer mycolic acid-containing membrane ...
The type VI secretion system (T6SS) is molecular machine used by a wide range of Gram-negative bacterial species to transport proteins from the interior (cytoplasm or cytosol) of a bacterial cell across the cellular envelope into an adjacent target cell. The T6SS was first identified in 2006 in Vibrio cholerae, which causes cholera. Since then, Type VI secretion systems have been found in a quarter of all Proteobacterial genomes, including pathogens of animals, plants, and humans, as well as soil, environmental or marine bacteria. While most of the early studies of Type VI secretion focused on its role in the pathogenesis of higher organisms, it is now known to function primarily in interbacterial antagonism. The T6SS is thought to resemble an inverted phage extending outward from the bacterial cell surface. It consists of 14 proteins that assemble into three sub-complexes: a phage tail-like tubule, a phage baseplate-like structure, and cell-envelope spanning membrane complex. These three ...
Type VII protein secretion (T7SS) is a specialised system for excreting extracellular proteins across bacterial cell membranes and has been associated with virulence in Staphylococcus aureus. The genetic diversity of the ess locus, which encodes the T7SS, and the functions of proteins encoded within it are poorly understood. We used whole genome sequence data from 153 isolates representative of the diversity of the species to investigate the genetic variability of T7SS across S. aureus. The ess loci were found to comprise of four distinct modules based on gene content and relative conservation. Modules 1 and 4, comprising of the 5 and 3 modules of the ess locus, contained the most conserved clusters of genes across the species. Module 1 contained genes encoding the secreted protein EsxA, and the EsaAB and EssAB components of the T7SS machinery, and Module 4 contained two functionally uncharacterized conserved membrane proteins. Across the species four variants of Module 2 were identified containing
Gram-negative bacteria secrete a wide range of proteins whose functions include biogenesis of organelles, such as pilli and flagella, nutrient acquisition, virulence, and efflux of drugs and other toxins. Six distinct secretion systems have been shown to mediate protein export through the inner and outer membranes of Gram-negative bacteria. These pathways are highly conserved throughout the Gram-negative bacterial species. In Gram-positive bacteria, secreted proteins are commonly translocated across the single membrane by the Sec pathway or the two-arginine (Tat) pathway ...
Pseudomonas syringae is a bacterial plant pathogen that infects a large variety of agricultural crops. Bacteria colonize leaf surfaces and enter plant mesophyll tissue through wounds or stomata. Once inside, P. syringae can alter plant cell signaling pathways and suppress plant defense responses enabling it to grow in the intercellular space in the mesophyll. P. syringae possesses at least two types of virulence factors that suppress plant defense responses: i) small phytotoxin molecules, and ii) effector proteins that are translocated through specialized secretion systems. Gram-negative bacteria possess at least six types of secretion systems. The P. syringae type II and type III secretion systems (T2SS and T3SS) are both involved in secreting proteins that are important for P. syringae pathogenesis. Functions of the other secretion systems have not been explored. This study investigates the role of the newly discovered type VI secretion system (T6SS) in P. syringae interaction with plants. The
TY - JOUR. T1 - Heterogeneity in ess transcriptional organization and variable contribution of the Ess/Type VII protein secretion system to virulence across closely related Staphylocccus aureus strains. AU - Kneuper, Holger. AU - Cao, Zhen Ping. AU - Twomey, Kate B.. AU - Zoltner, Martin. AU - Jäger, Franziska. AU - Cargill, James S.. AU - Chalmers, James. AU - van der Kooi-Pol, Magdalena M.. AU - van Dijl, Jan Maarten. AU - Ryan, Robert P.. AU - Hunter, William N.. AU - Palmer, Tracy. N1 - © 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.. PY - 2014/7/30. Y1 - 2014/7/30. N2 - The Type VII protein secretion system, found in Gram-positive bacteria, secretes small proteins, containing a conserved W-x-G amino acid sequence motif, to the growth medium. Staphylococcus aureus has a conserved Type VII secretion system, termed Ess, which is dispensable for laboratory growth but required for virulence. In this study we show that there are unexpected differences in the ...
Marie-Stéphanie Aschtgen, Mark Thomas, E. Cascales. Anchoring the type VI secretion system to the peptidoglycan: TssL, TagL, TagP... what else?. Virulence, Taylor & Francis, 2014, 1 (6), pp.535-540. ⟨10.4161/viru.1.6.13732⟩. ⟨hal-03274811⟩ ...
Type III secretion systems enable plant and animal bacterial pathogens to deliver virulence proteins into the cytosol of eukaryotic host cells, causing a broad spectrum of diseases including bacteremia, septicemia, typhoid fever, and bubonic plague in mammals, and localized lesions, systemic wilting, and blights in plants. In addition, type III secretion systems are also required for biogenesis of the bacterial flagellum. The HrcQ(B) protein, a component of the secretion apparatus of Pseudomonas syringae with homologues in all type III systems, has a variable N-terminal and a conserved C-terminal domain (HrcQ(B)-C). Here, we report the crystal structure of HrcQ(B)-C and show that this domain retains the ability of the full-length protein to interact with other type III components. A 3D analysis of sequence conservation patterns reveals two clusters of residues potentially involved in protein-protein interactions. Based on the analogies between HrcQ(B) and its flagellum homologues, we propose ...
PROJECT SUMMARYThe transmission of macromolecules across biological membranes is a fundamental process in all cells. In theearliest studies of genetic exchange in bacteria dating back to the 1940s, the F plasmid (then termed `sexfactor) was shown to self-transfer and, through recombination, mediate the transfer of the entire E. colichromosome to recipient bacteria. In the ensuing ~75 years, studies established the broad medical importanceof F and other mobile genetic elements (MGEs) in the shaping of bacterial genomes and as vectors fordissemination of antibiotic resistance and other fitness traits among bacterial populations. MGEs also encodeconjugative pili or other cell surface adhesins, which promote intercellular contacts necessary for DNA transferand establishment robust, antibiotic-resistant biofilm communities. MGEs are transmitted intercellularly throughnanomachines termed type IV secretion systems (T4SSs). The T4SSs are present in most if not all bacterialspecies, where they have ...
The human colonic microbiota is a dense ecosystem comprised of numerous microbes, including bacteria, phage, fungi, archaea, and protozoa, that compete for nutrients and space. Studies are beginning to reveal the antagonistic mechanisms that gut bacteria use to compete with other members of this ecosystem. In the healthy human colon, the majority of the Gram-negative bacteria are of the order Bacteroidales. Proteobacteria, such as Escherichia coli, are numerically fewer but confer important properties to the host, such as colonization resistance. Several enteric pathogens use type VI secretion systems (T6SSs) to antagonize symbiotic gut E. coli, facilitating colonization and disease progression. T6SS loci are also widely distributed in human gut Bacteroidales, which includes three predominant genera: Bacteroides, Parabacteroides, and Prevotella. There are three distinct genetic architectures of T6SS loci among the gut Bacteroidales, termed GA1, GA2, and GA3. GA1 and GA2 T6SS loci are contained on
Scaffold proteins are ubiquitous chaperones that promote efficient interactions between partners of multi-enzymatic protein complexes; although they are well studied in eukaryotes, their role in prokaryotic systems is poorly understood. Bacterial membranes have functional membrane microdomains (FMM), a structure homologous to eukaryotic lipid rafts. Similar to their eukaryotic counterparts, bacterial FMM harbor a scaffold protein termed flotillin that is thought to promote interactions between proteins spatially confined to the FMM. Here we used biochemical approaches to define the scaffold activity of the flotillin homolog FloA of the human pathogen Staphylococcus aureus, using assembly of interacting protein partners of the type VII secretion system (T7SS) as a case study. Staphylococcus aureus cells that lacked FloA showed reduced T7SS function, and thus reduced secretion of T7SS-related effectors, probably due to the supporting scaffold activity of flotillin. We found that the presence of ...
Tuberculosis is a leading cause of death globally. The causative agent, Mycobacterium tuberculosis, resides primarily in so-called macrophages, a type of immune cell that normally serves to kill invading bacteria. The mycobacterial ESX-1 type VII secretion system is critical for ability of the bacterium to survive and grow in these cells. Moreover, ESX-1 is known to induce secretion of proinflammatory cytokines, including IL-1ß, as well as cell death to infected cells. Because these functions may have important roles during infection, this project aimed to gain insight into mechanistic basis for ESX-1-induced IL-1 ß secretion and cell death, respectively ...
Mycobacterium abscessus, a rapidly growing mycobacterium (RGM) and an opportunistic human pathogen, is responsible for a wide spectrum of clinical manifestations ranging from pulmonary to skin and soft tissue infections. This intracellular organism can resist the bactericidal defense mechanisms of amoebae and macrophages, an ability that has not been observed in other RGM. M. abscessus can up-regulate several virulence factors during transient infection of amoebae, thereby becoming more virulent in subsequent respiratory infections in mice. Here, we sought to identify the M. abscessus genes required for replication within amoebae. To this end, we constructed and screened a transposon (Tn) insertion library of an M. abscessus subspecies massiliense clinical isolate for attenuated clones. This approach identified five genes within the ESX-4 locus, which in M. abscessus encodes an ESX-4 type VII secretion system that exceptionally also includes the ESX conserved EccE component. To confirm the ...
Mechanistic insights into the role of the three genes induced by pulmonary surfactant in S. aureus virulence.The present study demonstrated that the essC, psiS, and hlgB gene expression levels were increased by treatment with surfactant. In this section, we discuss the relationships between our results and previous reports concerning the involvement of the three genes in pathogenesis.. The essC gene is a member of the ess cluster, a genomic region that contains the esxAB, esaABC, and essABC genes and is conserved in Gram-positive bacteria such as Listeria monocytogenes, Bacillus thuringiensis, and Mycobacterium tuberculosis (43). The ess genes encode components of the type VII secretion system, a recently identified Sec-independent secretion pathway of bacteria that is involved in virulence via the secretion of various toxins, including EsxA, EsxB, and EsaC (43-45). Interestingly, the amount of EsaC secreted into the blood increases when S. aureus infects host animals (43). Based on these ...
Expert authors critically review selected important topics in the field of bacterial pathogenesis. A valuable resource. Topics range from a review of the seven most important bacterial secretion systems to an overview of evasion strategies of mycobacteria. Essential reading.
The type VI secretion system (T6SS) has emerged as an important mediator of interbacterial interactions. A T6SS from Pseudomonas aeruginosa targets at least three effector proteins, \(\underline t\)ype VI \(\underline s\)ecretion \(\underline e\)xported 1-3 (Tse1-3), to recipient Gram-negative cells. The Tse2 protein is a cytoplasmic effector that acts as a potent inhibitor of target cell proliferation, thus providing a pronounced fitness advantage for P. aeruginosa donor cells. P. aeruginosa utilizes a dedicated immunity protein, \(\underline t\)ype VI \(\underline s\)ecretion \(\underline i\)mmunity 2 (Tsi2), to protect against endogenous and intercellularly-transferred Tse2. Here we show that Tse2 delivered by the T6SS efficiently induces quiescence, not death, within recipient cells. We demonstrate that despite direct interaction of Tsi2 and Tse2 in the cytoplasm, Tsi2 is dispensable for targeting the toxin to the secretory apparatus. To gain insights into the molecular basis of Tse2 ...
The assembly of the T3SS culminates in the formation of the needle filament [Fig. 2 (10)]. Beyond the base, export apparatus and cytosolic components, which are required for substrate secretion per se, correct formation of the needle filament requires the co-secretion of other early substrates, including the inner rod protein and the needle length regulator [Fig. 2 (10)] (Kimbrough & Miller, 2000; Kubori et al., 2000). In some systems, secretion of needle subunits is assisted by dedicated chaperones that prevent premature filament formation in the bacterial cytosol (Quinaud et al., 2005, 2007; Sun et al., 2008; Chatterjee et al., 2011; Sal-Man et al., 2013). It was shown that secretion of the needle filament subunit is required for export of the other proteins (Kimbrough & Miller, 2000). Marlovits et al. (2006) subsequently observed that variations in the expression ratio of the Salmonella inner rod protein PrgJ and the needle subunit PrgI resulted in changes in needle length and concluded that ...
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This invention relates to a surgical device and methods for accessing and retrieving a tissue mass from a body cavity through a minimally invasive laparoscopic procedure. The device consists of a handle comprising an inner rod, which is rotatably engaged within a tubular member, and a loop adapted to hold a surgical bag. The loop comprises first and second bowed leaf elements, wherein the first bowed leaf element is attached to the inner rod and the second bowed leaf element is attached to the tubular member. The device further has a rotatable articulation, such as a hinge, joining the first and second bowed leaf elements, wherein rotation of the inner rod causes the first bowed leaf element to rotate about the articulation, such that the surgical bag may be opened and closed by rotation of the inner rod.
Bacterial secretory signal peptide expression plasmid with the T7 promoter upstream to drive gene expression (Frame 1 - NcoI site aligned).
The closely related type III secretion system zinc metalloprotease effector proteins GtgA, GogA, and PipA are translocated into host cells during infection. They then cleave nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) transcription factor subunits, dampening activation of the NF-κB signaling pathway and thereby suppressing host immune responses. We demonstrate here that GtgA, GogA, and PipA cleave a subset of NF-κB subunits, including p65, RelB, and cRel but not NF-κB1 and NF-κB2, whereas the functionally similar type III secretion system effector NleC of enteropathogenic and enterohemorrhagic cleaved all five NF-κB subunits. Mutational analysis of NF-κB subunits revealed that a single nonconserved residue in NF-κB1 and NF-κB2 that corresponds to the P1 residue Arg-41 in p65 prevents cleavage of these subunits by GtgA, GogA, and PipA, explaining the observed substrate specificity of these enzymes. Crystal structures of GtgA in its apo-form and in complex with ...
The sort VI secretion system (T6SS) is a bacterial nanomachine for the transport of effector molecules into prokaryotic and eukaryotic cells. the existence of distinct T6SS classes. An accessory T6SS component, TagJ/HsiE, exists predominantly in one of the classes. Using bacterial two-hybrid approaches, we showed that the homolog HsiE1 interacts strongly with ClpV1. We then resolved the crystal structure of HsiE1 in complex with the N terminus of HsiB1, a TssB homolog and component of the contractile sheath. Phylogenetic analysis confirmed that these differences distinguish T6SS classes that resulted from a functional co-evolution between TssB, TssC, TagJ/HsiE, and ClpV. The interaction of TagJ/HsiE with the sheath as well as with ClpV suggests an alternative mode of disassembly in which HsiE recruits the ATPase to the sheath. mutant has a reduced T6SS-dependent killing activity toward VipA/VipB sheath (TssB/TssC homologs) (20, 21, 27) is dependent on a direct interaction between ClpV and ...
Typically comprised of ~12 different scaffold components, prokaryotic type IV secretion systems (T4SSs) translocate a variety of substrates across the cell envelope. Due to the ability to translocate large DNA segments (i.e., mobile genetic elements), some T4SSs contribute to the spread of antimicrobial resistance and virulence genes. Other T4SSs translocate smaller DNA segments and/or proteins into eukaryotic cells (e.g., arthropod, plant and human) in order to benefit bacterial survival. At least eight major groups of T4SSs are described and each group consists of minor variations on a common structural theme. Within a given bacterial genome, combinations of different T4SS groups can be encoded, and sometimes multiple copies of the same T4SS group can be present. As an example, two functionally divergent T4SSs (vir and trw) are found in many species of Bartonella, bacteria that are transmitted by arthropods such as ticks and fleas and cause a range of diseases including endocarditis. In species of
Type III secretion systems (T3SS) in phytopathogenic bacteria were first described in the 80s. However, whereas numerous characterization studies have revealed the basic processes of assembly, structure and function in animal/human pathogenic systems, our knowledge about these processes in plant type III biosystems is considerably small in comparison. Nonetheless, in recent years we have witnessed important breakthroughs in our understanding on how phytopathogens employ, build and regulate their T3SS: new master transcriptional regulators have been discovered, the activity of already described regulators of the system have been thoroughly investigated, quorum sensing regulators and population dynamics have been found to determine the fine activation of the system, new plant-derived signals have been found to upregulate the phytopathogenic T3SS, and more. Moreover, a considerable weaponry of effectors targeting and tuning the plant responses have been identified and protein components of the core
Friday, 26 January 2018, 13:00Add to calendarESX type VII secretion key to mycobacterial host-pathogen interaction Roland Brosch, Institut Pasteur, Integrated Mycobacterial Pathogenomics Unit, 25 Rue du Dr Roux, 75015 Paris, FranceHost: Matthias WilmannsSeminar Room 48e, EMBL Hamburg ...
Microbial communities are shaped by interactions among their constituent members. Some Gram-negative bacteria employ type VI secretion systems (T6SSs) to inject protein toxins into neighboring cells. These interactions have been theorized to affect the composition of host-associated microbiomes, but the role of T6SSs in the evolution of gut communities is not well understood. We report the discovery of two T6SSs and numerous T6SS-associated Rhs toxins within the gut bacteria of honey bees and bumble bees. We sequenced the genomes of 28 strains of Snodgrassella alvi, a characteristic bee gut microbe, and found tremendous variability in their Rhs toxin complements: altogether, these strains appear to encode hundreds of unique toxins ...
Type-III secretion systems (T3SSs) are responsible for the biosynthesis of flagella, and the interaction of many animal and plant pathogens with eukaryotic cells. T3SSs consist of multiple proteins which assemble to form an apparatus capable of exporting proteins through both membranes of Gram-negative bacteria in one step. Proteins conserved amongst T3SSS can be used for analysis of these systems using computational homology searching. By using tools including BLAST and HMMER in conjunction phylogenetic analysis this thesis examines the range of T3SSs, both in terms of the proteins they contain, and also the bacteria which contain them. In silico analysis of several of the conserved components of T3SSs shows similarities between them and other secretion systems, as well as components of ATPases. Use of conserved components allows for identification of T3SS loci in diverse bacteria, in order to assess in the different proteins used by different T3SSs, and to see where, in evolutionary space, ...
T346Hunter :: DESCRIPTION T346Hunter is a web application for the identification of type III, type IV and type VI secretion systems (T3SS, T4SS and T6SS, respectively) in bacterial genomes. ::DEVELOPER T346Hunt
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Killing for DNA: The type VI secretion system of Vibrio cholerae fosters horizontal gene transfer 11.30 - 11.45 Leendert Hamoen, University of Amsterdam, ...
This volume discusses various basic and advanced methods and protocols that have been proven to be successful among certain bacterial species, or a family of species, in type III secretion systems (T3
Korotkov, K. V., T. L. Johnson, M. G. Jobling, J. Pruneda, E. Pardon, A. Héroux, S. Turley, J. Steyaert, R. K. Holmes, M. Sandkvist, et al., Structural and functional studies on the interaction of GspC and GspD in the type II secretion system., PLoS Pathog, vol. 7, issue 9, pp. e1002228, 2011 Sep. ...
Genetic information processingProtein fateProtein and peptide secretion and traffickingtype VII secretion protein EssC (TIGR03928; HMM-score: 129.6) ...
Whether its through a lab mishap or eating undercooked beef, becoming infected with pathogenic (disease-causing) E. coli is brutal. When E. coli infects a person, it attaches to the intestinal wall and the infection begins. There is a particular set of proteins that E. coli makes that allow the bacterium to be incredibly successful at infection. These structures, called the Type III secretion system, look and act like tiny syringes. They essentially inject their own DNA and proteins into the hosts cells. Not only do E. coli use Type III secretion to wreak havoc on the host, but they also can release a chemical called Shiga toxin. This toxin can enter cells, disrupt host protein synthesis, and even burst the intestinal cells. A build up of this toxin is extremely detrimental to the host. Although E. coli infections are relatively uncommon, they are serious business and cant be taken lightly. Now, I dont want you to think all E. coli are bad guys. Most E. coli are an integral part of our ...
Many gram-negative plant pathogenic bacteria have acquired a highly conserved type III secretion system (T3SS) which enables them to inject so called ... ...
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
ssdo | ssdodge | ssdo9 | ssdog | ssdoi | ssdoc | ssdoh | ssdoj | ssdon | ssdor | ssdow | ssdoy | ssdob24 | ssdofla | ssdoor | ssdob.cc | ssdojrp | ssdortal | ss
Paleontologists still poorly understand the process that sorts the winners from the losers after a major extinction, Jablonski said. His statistical analysis ruled out one of the most straightforward of possible causes - that lineages that have suffered a major blow to their numbers during a mass extinction might be especially extinction-prone in the aftermath because they contain fewer species to buffer against the hard times. Instead, Jablonski found that many of the biggest post-extinction winners had passed through a diversity bottleneck as narrow as the Dead Clade Walking groups ...
The structure of the Tse3-Tsi3 complex associated with the bacterial type VI secretion system of P. aeruginosa has been solved and refined at 1.9 Å resolution. The structural basis of the recognition of the muramidase effector and its inactivation by its cognate immunity protein is revealed. The type VI secretion system (T6SS) is a bacterial protein-export machine that is capable of delivering virulence effectors between Gram-negative bacteria. The T6SS of Pseudomonas aeruginosa transports two lytic enzymes, Tse1 and Tse3, to degrade cell-wall peptidoglycan in the periplasm of rival bacteria that are competing for niches via amidase and muramidase activities, respectively. Two cognate immunity proteins, Tsi1 and Tsi3, are produced by the bacterium to inactivate the two antibacterial effectors, thereby protecting its siblings from self-intoxication. Recently, Tse1-Tsi1 has been structurally characterized. Here, the structure of the Tse3-Tsi3 complex is reported at 1.9 Å resolution. The results ...
Burkholderia cenocepacia is an opportunistic pathogen causing life-threatening infections in cystic fibrosis and other immunocompromised patients. The bacterium survives within macrophages by interfering with typical endocytic trafficking, resulting in delayed maturation of a B. cenocepacia-containing phagosome. We hypothesize that B. cenocepacia alters gene expression after internalization by macrophages, inducing genes involved in intracellular survival and host adaptation. Furthermore, we hypothesize that specialized bacterial secretion systems are involved in the interactions between intracellular bacteria and macrophages. In this work, we characterize later-stage infection of macrophages by B. cenocepacia, showing replication within an acidified endosomal compartment suggestive of a phagolysosome. We examine differential gene expression by intracellular B. cenocepacia using selective capture of transcribed sequences (SCOTS) with both competitive enrichment and microarray analysis. We identified 766
The EsxA/B protein secretion pathway system (EPSP) (Anderson et al. 2011; Burts et al. 2005; Chen et al. 2012; Sundaramoorthy et al. 2008). EssC is an integral component of the bacterial Type VII secretion system (T7SS). The protein is predicted to consist of an intracellular repeat of forkhead-associated (FHA) domains at the N-terminus, two transmembrane helices and three P-loop containing ATPase-type domains, D1-3, forming the C-terminal intracellular segment. Zoltner et al. 2016 presented crystal structures of the N-terminal FHA domains (EssC-N) and a C-terminal fragment EssC-C from Geobacillus thermodenitrificans, encompassing two of the ATPase-type modules, D2 and D3. Module D2 binds ATP with high affinity whereas D3 does not. The EssC-N and EssC-C constructs are monomeric in solution but the full-length recombinant protein, with molecular weight about 169 kDa, forms a multimer of approximately 1 MDa. The observation of protomer contacts in the crystal structure of EssC-C together with ...
The major research focus of my group is the transport of proteins by the twin arginine protein transport pathway. This pathway, which is found in the cytoplasmic membranes of most bacteria, and the thylakoid membranes of plant chloroplasts, is highly unusual because it transports pre-folded proteins. Protein substrates are targeted to the Tat machinery by N-terminal signal peptides that contain an S/T- R-R-x-F-L-K twin arginine motif. Our aims are to study the function and mechanism of the Tat protein transporter, and the contribution that it makes to the physiology of bacteria. The Gram-positive bacterium Staphylococcus aureus uses an unusual Type VII secretion system to secrete possible virulence factors. In a collaboration with Professor Bill Hunter we have been structurally and biochemically characterising components and substrates of this system. Contact details ...
Infection with Citrobacter rodentium triggers robust tissue damage repair responses, manifested by secretion of IL-22, in the absence of which mice succumbed
T4SSs each possess an envelope-spanning channel composed of conserved components termed the core complex. Early biochemical studies showed that VirB7, VirB9 and VirB10 form a transporter subassembly that is both intrinsically stable and stabilizing for other VirB subunits. This core complex from the conjugative pKM101 system provided the first high-resolution images [26]. The core secretion channel is a multimeric VirB7-VirB9-VirB10 complex containing 14 copies of each protein. A cylindrical structure spanning the entire cell envelope is composed of two layers (designated I and O). Each layer forms a double-walled ring-like structure that defines hollow chambers inside the complex (figure 3b). The structure surrounds a central chamber of about 80 Å at its widest point. The N-terminal domains (NTDs) of VirB9 and VirB10 comprise the I layer and this part of the channel is anchored in the IM by an N-terminal transmembrane helix of VirB10. An opening at the base of the I layer spans 55 Å. The O ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
A retractable needle syringe includes a barrel defining a receiver. There is a plunger having an inner rod extending distally from the proximal end. The plunger includes a hollow sleeve that is disposed over and extend beyond an inner rod. The plunger includes a hollow cutter extending from the inner rod and a stopper disposed over the end of the sleeve. The plunger has a displaceable collar to prevent movement of the inner rod with respect to the sleeve, that is by distal force to the plunger by engagement with the proximal end of the barrel allowing the cutting surface to cut through the stopper. There is a hub with a stem, a proximal flange and an engagement. A clip having a proximal foot with an opening therethrough and a distal grip is disposed on the stem of the hub. The proximal foot of the clip is disposed at the distal surface of the flange and the grip at the engagement on the stem. There is a spring disposed about the stem compressed between the receiver and the clip to provide a bias, so
A suture driver for clamping a suture in the hollow passage and a recessed channel thereof and manipulating the suture to and from a surgical site. The driver includes an outer member tube having a closed and pointed distal end for percutaneous introduction into the body of a patient. The outer tube also includes a recessed channel positioned proximal the closed distal end of the hollow passage extending longitudinally therein and for receiving the suture therein. An inner rod is positioned in the passage of the outer tube and has a clamping surface at the distal end thereof for engaging a suture positioned in the recessed channel. The inner rod is slid through the recessed channel to clamp the suture in the hollow passage of the outer tube against another clamping surface at the distal end of the tube. A handle positioned at the proximal end of the outer tube and inner rod is manipulated to slide the inner rod through the recessed channel and clamp the suture in the hollow passage between the two
Type IV secretion systems (T4SSs) mediate horizontal gene transfer, thus contributing to genome plasticity, evolution of infectious pathogens, and dissemination of antibiotic resistance and other virulence traits. A gene cluster of the Haemophilus influenzae genomic island ICEHin1056 has been identified as a T4SS involved in the propagation of genomic islands. This T4SS is novel and evolutionarily distant from the previously described systems. Mutation analysis showed that inactivation of key genes of this system resulted in a loss of phenotypic traits provided by a T4SS. Seven of 10 mutants with a mutation in this T4SS did not express the type IV secretion pilus. Correspondingly, disruption of the genes resulted in up to 100,000-fold reductions in conjugation frequencies compared to those of the parent strain. Moreover, the expression of this T4SS was found to be positively regulated by one of its components, the tfc24 gene. We concluded that this gene cluster represents a novel family of T4SSs
Time-lapse microscopy analysis has revealed that T6SS organelles in V. cholerae cells are very dynamic and likely secrete their T6SS spike/tube VgrG/Hcp complex in multiple directions over a period of minutes of observation (6). Such constitutive activity is likely to result in the attack of neighboring sister cells under conditions of growth on solid media or within biofilms. Therefore, it is not surprising that immunity proteins would evolve in T6SS+ species to resist the toxicity associated with the attack of sister cells.. In this study, we report three immunity genes and their corresponding effectors in V. cholerae. Inactivation of any of three immunity genes results in susceptibility to T6SS-dependent killing by T6SS+ strain V52. Deletion of any of the three cognate effectors in V52 abolishes killing of the mutant defective in the corresponding immunity protein. The identified effector-immunity proteins share no homology with other known T6SS effector-immunity pairs, indicating the ...
The type III secretion system (T3SS) plays an important role in the pathogenesis of Pseudomonas aeruginosa. Expression of the T3SS is controlled under a complicate regulatory network. In this study, we demonstrate that NrtR (PA4916) is involved in the T3SS expression and pathogenesis of P. aeruginosa in a mouse acute pneumonia model. Overexpression of the T3SS central activator ExsA or exogenous supplementation of cAMP restored the expression of T3SS in the ΔnrtR mutant, suggesting that NrtR might regulate T3SS through the cAMP-Vfr signaling pathway. Further experiments demonstrated that the decrease of cAMP content is not due to the expression change of adenylate cyclases or phosphodiesterase in the ΔnrtR mutant. As it has been shown that nadD2 is upregulated in the ΔnrtR mutant, we overexpressed nadD2 in wild type PAK, which reduced the intracellular cAMP level and the expression of the T3SS genes. Meanwhile, deletion of nadD2 in the ΔnrtR mutant restored the expression and secretion of the T3SS.
The dissemination of multi-resistant bacteria represents an enormous burden on modern healthcare. Plasmid-borne conjugative transfer is the most prevalent mechanism, requiring a type IV secretion system that enables bacteria to spread beneficial traits, such as resistance to last-line antibiotics, among different genera. Inc18 plasmids, like the Gram-positive broad host-range plasmid pIP501, are substantially involved in propagation of vancomycin resistance from Enterococci to methicillin-resistant strains of Staphylococcus aureus. Here, we identified the small cytosolic protein TraN as a repressor of the pIP501-encoded conjugative transfer system, since deletion of traN resulted in upregulation of transfer factors, leading to highly enhanced conjugative transfer. Furthermore, we report the complex structure of TraN with DNA and define the exact sequence of its binding motif. Targeting this protein-DNA interaction might represent a novel therapeutic approach against the spreading of antibiotic ...
Enterohemorrhagic Escherichia coli (EHEC) is a common cause of severe hemorrhagic colitis. EHECs virulence is dependent upon a type III secretion system (TTSS) encoded by 41 genes. These genes are organized in several operons clustered in the locus of enterocyte effacement. Most of the locus of enterocyte effacement genes, including grlA and grlR, are positively regulated by Ler, and Ler expression is positively and negatively modulated by GrlA and GrlR, respectively. However, the molecular basis for the GrlA and GrlR activity is still elusive. We have determined the crystal structure of GrlR at 1.9 Å resolution. It consists of a typical β-barrel fold with eight β-strands containing an internal hydrophobic cavity and a plug-like loop on one side of the barrel. Strong hydrophobic interactions between the two β-barrels maintain the dimeric architecture of GrlR. Furthermore, a unique surface-exposed EDED (Glu-Asp-Glu-Asp) motif is identified to be critical for GrlA-GrlR interaction and for the ...
3. Vincent CD, Jeong KC, Sexton J, Buford E, Vogel JP. 2006. The Legionella pneumophila Dot/Icm Type IV Secretion System. In Legionella: State of the Art 30 Years After Its Recognition. Ed. N. Cianciotto et al, ASM Press, Washington, D.C. Pages 184-191 ...
CP000828.PILC Location/Qualifiers FT CDS_pept complement(390490..391710) FT /codon_start=1 FT /transl_table=11 FT /gene=pilC FT /locus_tag=AM1_0417 FT /product=type II secretion system domain protein/ pilin FT biogenesis protein PilC FT /note=Member of bacterial type II secretion system protein FT F domain, PF00482. FT /db_xref=EnsemblGenomes-Gn:AM1_0417 FT /db_xref=EnsemblGenomes-Tr:ABW25474 FT /db_xref=GOA:B0CAY4 FT /db_xref=InterPro:IPR001992 FT /db_xref=InterPro:IPR003004 FT /db_xref=InterPro:IPR018076 FT /db_xref=InterPro:IPR042094 FT /db_xref=UniProtKB/TrEMBL:B0CAY4 FT /protein_id=ABW25474.1 FT /translation=MPTYVVRARDSQGKSSQKRVNATSQKEARSNIQRQGLQILDIKES FT QGFSMNAELDLSFLQSITVKDKALFSRQFSALVNAGVALVRGLGVMSEQCKNPKLKKAL FT LDVNAAVQQGVSLSDAMRGHPAAFDQLYVAMIQAGETGGVLDEVLNRLATLLEDQARLK FT NQIRSALAYPVVVGFIAVSIFLGMVIFLIPVFDGIFSQLGGDLPAFTQFMVNLSEFLRT FT PIYGISAAIVVFGSTFALRQYYRTRAGRETIDRIMLKLPLFGDLIQKTAVARFCRTFGS FT LSRSGVPILYSLEIVRDTAGNQVVSNAIDEARREIQGGGMLSLALQKEKVFPLLATQMI ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
The type IV secretion system virB/virD4 is a major virulence determinant for subversion of human endothelial cell (HEC) function. VirB-dependent changes of HEC include massive cytoskeletal rearrangements, a proinflammatory activation by nuclear factor NF-kappa-B, inhibition of early and late events of apoptosis, leading to an increased cell survival, and, at high infection doses, a cytostatic or cytotoxic effect, which interfers with a potent virB-independent mitogenic activity. These changes of HEC require the T4S coupling protein virD4 and at least one of the effector proteins bepA-G. Together with virB11, may be implicated in providing the energy, via hydrolysis of ATP, for the assembly of secretion system and substrate transport ...
Genes in the 5-kb flanking regions if available, or non-core components encoded by the T6SS gene cluster if any. In the Note column,if available, (e) denotes effector while (i) for immunity ...
Genes in the 5-kb flanking regions if available, or non-core components encoded by the T6SS gene cluster if any. In the Note column,if available, (e) denotes effector while (i) for immunity ...