SEARCH · PubMed Health

Results for “Secretion systems”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 595 records · Page 33Linked to original sources

PubMed2005

The type III needle and the damage done.

Many Gram-negative pathogens translocate virulence proteins directly into host cells using a type III secretion system. This complex secretion machinery is composed of approximately 25 different proteins that assemble to span both bacterial membranes, and contact the host cell to form a direct channel between the bacterial and host cell cytoplasms. Assembly of the system and efficient secretion of virulence proteins through this apparatus require specific chaperones. Although the machinery is morphologically conserved among all bacteria, the secreted proteins vary widely and are responsible for the range of diseases caused by bacterial pathogens. Recent structures have given insights into important chaperone and effector proteins, as well as revealing the first atomic structures of portions of the secretion machinery itself.

Bacterial Proteins↗

PubMed2001

Prevalence of type III secretion genes in clinical and environmental isolates of Pseudomonas aeruginosa.

The type III secretion system of Pseudomonas aeruginosa transports four known effector proteins: ExoS, ExoT, ExoU and ExoY. However, the prevalence of the type III secretion system genes or the effector-encoding genes in clinical and environmental isolates of P. aeruginosa has not been well studied. Southern hybridization analyses and PCR were performed on over 100 P. aeruginosa isolates to determine the distribution of these genes. Clinical isolates were obtained from urine, endotracheal, blood and wound specimens, from the sputum of cystic fibrosis (CF) patients, and from non-hospital environmental sites. The popB gene was used as a marker for the presence of the large chromosomal locus encoding the type III secretion machinery proteins. Each isolate contained the popB gene, indicating that at least a portion of this large chromosomal locus was present in all isolates. Likewise, each isolate contained exoT-like sequences. In contrast, the exoS, exoU and exoY genes were variable traits. Overall, 72% of examined isolates contained the exoS gene, 28% contained the exoU gene, and 89% contained the exoY gene. Interestingly, an inverse correlation was noted between the presence of the exoS and exoU genes in that all isolates except two contained either exoS or exoU but not both. No significant difference in exoS, exoU or exoY prevalence was observed between clinical and environmental isolates or between isolates cultured from different disease sites except for CF respiratory isolates. CF isolates harboured the exoU gene less frequently and the exoS gene more frequently than did isolates from some of the other sites of infection, including the respiratory tract of patients without CF. These results suggest that the P. aeruginosa type III secretion system is present in nearly all clinical and environmental isolates but that individual isolates and populations of isolates from distinct disease sites differ in their effector genotypes. The ubiquity of type III secretion genes in clinical isolates is consistent with an important role for this system in human disease.

Bacterial Proteins↗

PubMed1992

[Functional system of secretion in renal tuberculosis].

Data are given on the study of functional correlations of the pairs of organs (kidneys-liver and kidneys-lungs) that participate in provision of the functional system of secretion. The correlation of these pairs of organs contribution to the total secretion of metabolites as renal insufficiency grows is characterized by the S-shaped dependence, i.e. by a compensatory increase of the conjoined functions at the early stages and its depression at the graver stages of renal insufficiency. This approach makes it possible to determine the character, terms and significance of the participation of various organs in provision of metabolic homeostasis maintenance long before its failure and to reveal the main links in the pathogenesis of functional disorders of secretion.

Chlormerodrin↗

PubMed2001

Recombinant attenuated bacteria for the delivery of subunit vaccines.

Using attenuated intracellular bacteria as carriers, we have developed two different approaches for the delivery of subunit vaccines encoding heterologous antigens. The first system is based on the direct secretion of the heterologous antigens in Gram-negative bacteria via the hemolysin secretion system of Escherichia coli into either phagosome or cytosol of infected cells. The second approach is based on the transport of eukaryotic antigen expression vectors by intracellular bacteria like Listeria and Salmonella into the host cell and here, preferably, into the cytosolic compartment. After release of the plasmid DNA from the bacteria, the plasmid-encoded antigens can be expressed directly by the host cell. Finally, we combined both types of subunit vaccines in one live vector - we equipped Salmonella strains with a phagosomal escape function by utilization of the hemolysin secretion system and used this recombinant vaccine strain for the delivery of a eukaryotic antigen expression vector into the cytosol of macrophages.

Animals↗

PubMed1997

The invasion-associated type III system of Salmonella typhimurium directs the translocation of Sip proteins into the host cell.

The ability of Salmonella typhimurium to interact with host cells is largely dependent on the function of a type III protein-secretion system encoded at centisome 63 of its chromosome. We have shown here that two targets of this protein-secretion system, SipB and SipC, are translocated into cultured intestinal Henle-407 cells. Translocation required the function of the type III secretion apparatus, as an S. typhimurium strain carrying a mutation in invA, which encodes an essential component of this system, failed to translocate the Sip proteins. Null mutations in the genes encoding SipB, SipC or SipD, prevented protein translocation, indicating that these proteins are involved in the translocation process. In contrast, mutations in sipA and sptP, which also encode secreted proteins, did not interfere with the translocation of SipC, indicating that only a subset of targets of the type III secretion system act as translocases. Externally or internally localized bacteria could direct protein translocation into Henle-407 cells as this process occurred in the presence of cytochalasin D at a concentration that prevented bacterial entry, or in the presence of gentamicin added shortly after bacterial internalization at a concentration that killed extracellular Salmonella. These results indicate that protein translocation into host cells may be a universal function of all type III secretion systems.

Animals↗

PubMed2004

Monitoring for dynamic biological processing by intramolecular bioluminescence resonance energy transfer system using secreted luciferase.

Proteolytic processing plays crucial roles in physiological and pathophysiological cellular functions such as peptide generation, cell cycle, and apoptosis. We developed a novel biophysical bioluminescence resonance energy transfer (BRET) system between a secreted Vargula luciferase (Vluc) and an enhanced yellow fluorescent protein (EYFP) for visualization of cell biological processes. The bioluminescence spectrum of the fusion protein (Vluc-EYFP) is bimodal (lambdamax = 460 nm (Vluc) and 525nm (EYFP)), indicating that the excited-state energy of Vluc transfers to EYFP (in short, BRET). The BRET signal can be measured in the culture medium and pursue quantitative production of two neuropeptides, nocistatin (NST) and nociceptin/orphanin FQ (N/OFQ) in living cells. NST and N/OFQ are located in tandem on the same precursor, but NST exhibits antagonistic action against N/OFQ-induced central functions. Insertion of a portion of the NST-N/OFQ precursor (Glu-Gln-Lys-Gln-Leu-Gln-Lys-Arg-Phe-Gly-Gly-Phe-Tyr-Gly) in Vluc-EYFP makes the fusion protein cleavable at Lys-Arg in NG108-15 cells, and proprotein convertase 1 enhances this digestion. The change in BRET signals quantifies the processing of the fusion protein. Our novel intramolecular BRET system using a secreted luciferase is useful for investigating peptide processing in living cells.

Bacterial Proteins↗

PubMed2006

Comparative genomics of Neisseria meningitidis: core genome, islands of horizontal transfer and pathogen-specific genes.

To better understand Neisseria meningitidis genomes and virulence, microarray comparative genome hybridization (mCGH) data were collected from one Neisseria cinerea, two Neisseria lactamica, two Neisseria gonorrhoeae and 48 Neisseria meningitidis isolates. For N. meningitidis, these isolates are from diverse clonal complexes, invasive and carriage strains, and all major serogroups. The microarray platform represented N. meningitidis strains MC58, Z2491 and FAM18, and N. gonorrhoeae FA1090. By comparing hybridization data to genome sequences, the core N. meningitidis genome and insertions/deletions (e.g. capsule locus, type I secretion system) related to pathogenicity were identified, including further characterization of the capsule locus, bioinformatics analysis of a type I secretion system, and identification of some metabolic pathways associated with intracellular survival in pathogens. Hybridization data clustered meningococcal isolates from similar clonal complexes that were distinguished by the differential presence of six distinct islands of horizontal transfer. Several of these islands contained prophage or other mobile elements, including a novel prophage and a transposon carrying portions of a type I secretion system. Acquisition of some genetic islands appears to have occurred in multiple lineages, including transfer between N. lactamica and N. meningitidis. However, island acquisition occurs infrequently, such that the genomic-level relationship is not obscured within clonal complexes. The N. meningitidis genome is characterized by the horizontal acquisition of multiple genetic islands; the study of these islands reveals important sets of genes varying between isolates and likely to be related to pathogenicity.

Bacterial Capsules↗

PubMed2004

Evidence in the Legionella pneumophila genome for exploitation of host cell functions and high genome plasticity.

Legionella pneumophila, the causative agent of Legionnaires' disease, replicates as an intracellular parasite of amoebae and persists in the environment as a free-living microbe. Here we have analyzed the complete genome sequences of L. pneumophila Paris (3,503,610 bp, 3,077 genes), an endemic strain that is predominant in France, and Lens (3,345,687 bp, 2,932 genes), an epidemic strain responsible for a major outbreak of disease in France. The L. pneumophila genomes show marked plasticity, with three different plasmids and with about 13% of the sequence differing between the two strains. Only strain Paris contains a type V secretion system, and its Lvh type IV secretion system is encoded by a 36-kb region that is either carried on a multicopy plasmid or integrated into the chromosome. Genetic mobility may enhance the versatility of L. pneumophila. Numerous genes encode eukaryotic-like proteins or motifs that are predicted to modulate host cell functions to the pathogen's advantage. The genome thus reflects the history and lifestyle of L. pneumophila, a human pathogen of macrophages that coevolved with fresh-water amoebae.

Adaptation, Biological↗

PubMed1989

Vacuolated plasma cell: ultrastructural distribution of acid phosphatase and intracellular immunoglobulin.

In two cases of vacuolated plasma cells, one of which was associated with primary macroglobulinemia and the other was with kappa-chain Bence Jones multiple myeloma, we examined the immunopathological features of the vacuoles in order to know whether the Ig-secreting system or the lysosomal system is of importance in the process of vacuole formation. Immunofluorescent studies detected no Ig in the vacuoles. Detection of intracellular Ig by immunoelectron microscopic technique revealed that Ig was localized only in a small portion of the vacuoles but not in most vacuoles. Even when Ig was included in the vacuoles, only the contents of the vacuoles were positive for Ig but their demarcating membrane was negative for Ig. In contrast, electron microscopic studies of acid phosphatase activity revealed the presence of its activity in all vacuoles. These findings suggest that the lysosomal system but not the Ig-secreting system may play a major role in vacuolation of these myeloma cells.

Acid Phosphatase↗

PubMed2006

Type III secretion: what's in a name?

The term 'type III secretion' has seen widespread use. However, problems persist in nomenclature. We propose that the standard abbreviation for this kind of secretion should be 'T3S' and that 'type III secretion system' should be abbreviated to 'T3SS'. There is also a need for a new terminology to distinguish flagellar and non-flagellar type III secretion systems that reflects their common evolutionary ancestry but does not obscure their distinctive features. Finally, the use of the term 'type III secretion' to cover cytolysin-mediated translocation is to be deprecated because an authentic type III secretion system has already been described in gram-positive bacteria, namely the flagellar protein export apparatus.

Endocytosis↗

PubMed1998

Interaction of enteropathogenic Escherichia coli with host epithelial cells.

Enteropathogenic Escherichia coli (EPEC) causes severe diarrhea in young children. Upon infection, EPEC induces the assembly of highly organized pedestal-like actin structures in host epithelial cells. All the EPEC genes that are involved in inducing formation of actin pedestals are located in a unique 35 kbp chromosomal pathogenicity island, termed LEE. These genes include the sep genes that encode components of type III protein secretion system, and genes that encode proteins secreted by this system, the esp genes. This protein secretion system is activated upon contact with the host cell, resulting in increased secretion of Esp proteins. Some of these Esp proteins from the translocation apparatus while others are translocated into the cytoplasm of the host cell. Concerted activity of the LEE genes including the eae, esp and the sep genes is needed to trigger signal transduction in the host cell which results in formation of an actin pedestal.

Diarrhea↗

PubMed1998

A novel EspA-associated surface organelle of enteropathogenic Escherichia coli involved in protein translocation into epithelial cells.

Enteropathogenic Escherichia coli (EPEC), like many bacterial pathogens, employ a type III secretion system to deliver effector proteins across the bacterial cell. In EPEC, four proteins are known to be exported by a type III secretion system_EspA, EspB and EspD required for subversion of host cell signal transduction pathways and a translocated intimin receptor (Tir) protein (formerly Hp90) which is tyrosine-phosphorylated following transfer to the host cell to become a receptor for intimin-mediated intimate attachment and 'attaching and effacing' (A/E) lesion formation. The structural basis for protein translocation has yet to be fully elucidated for any type III secretion system. Here, we describe a novel EspA-containing filamentous organelle that is present on the bacterial surface during the early stage of A/E lesion formation, forms a physical bridge between the bacterium and the infected eukaryotic cell surface and is required for the translocation of EspB into infected epithelial cells.

Adenylate Cyclase Toxin↗

PubMed1998

The medium is the messenger.

Enteropathogenic Escherichia coli (EPEC), like many bacterial pathogens, employ a type III secretion system to deliver effector proteins across the bacterial cell. In EPEC, four proteins are known to be exported by a type III secretion system--EspA, EspB and EspD required for subversion of host cell signal transduction pathways and a translocated intimin receptor (Tir) protein (formerly Hp90) which is tyrosine-phosphorylated following transfer to the host cell to become a receptor for intimin-mediated intimate attachment and "attaching and effacing" (A/E) lesion formation. The structural basis for protein translocation has yet to be fully elucidated for any type III secretion system. Here, we describe a novel EspA-containing filamentous organelle that is present on the bacterial surface during the early stage of A/E lesion formation, forms a physical bridge between the bacterium and the infected eukaryotic cell surface and is required for the translocation of EspB into infected epithelial cells.

Bacterial Adhesion↗

PubMed2003

Taking possession: biogenesis of the Salmonella-containing vacuole.

The Gram-negative pathogen Salmonella enterica can survive and replicate within a variety of mammalian cells. Regardless of the cell type, internalized bacteria survive and replicate within the Salmonella-containing vacuole, the biogenesis of which is dependent on bacterially encoded virulence factors. In particular, Type III secretion systems translocate bacterial effector proteins into the eukaryotic cell where they can specifically interact with a variety of targets. Salmonella has two distinct Type III secretion systems that are believed to have completely different functions. The SPI2 system is induced intracellularly and is required for intracellular survival in macrophages; it plays no role in invasion but is categorized as being required for Salmonella-containing vacuole biogenesis. In contrast, the SPI1 Type III secretion system is induced extracellularly and is essential for invasion of nonphagocytic cells. Its role in post-invasion processes has not been well studied. Recent studies indicate that Salmonella-containing vacuole biogenesis may be more dependent on SPI1 than previously believed. Other non-SPI2 virulence factors and the host cell itself may play critical roles in determining the intracellular environment of this facultative intracellular pathogen. In this review we discuss the recent advances in determining the mechanisms by which Salmonella regulate Salmonella-containing vacuole biogenesis and the implications of these findings.

Actins↗

PubMed1997

The Rhizobium meliloti exoK gene and prsD/prsE/exsH genes are components of independent degradative pathways which contribute to production of low-molecular-weight succinoglycan.

When grown on medium supplemented with the succinoglycan-binding dye, Calcofluor, and visualized under UV light, colonies of Rhizobium meliloti (Sinorhizobium meliloti) exoK mutants produce a fluorescent halo with a delayed onset relative to wild-type colonies. By conducting transposon mutagenesis of exoK mutants of R. meliloti and screening for colonies with even more severe delays in production of these fluorescent halos, we identified three genes, designated prsD, prsE, and exsH, which are required for the eventual production of fluorescent halos by exoK colonies. Nucleotide sequence indicates that the prsD and prsE genes encode homologues of ABC transporters and membrane fusion proteins of Type I secretion systems, respectively, whereas exsH encodes a homologue of endo-1,3-1,4-beta-glycanases with glycine-rich nonameric repeats typical of proteins secreted by Type I secretion systems. The exoK gene and the prsD/prsE/exsH genes were shown to be components of independent pathways for production of extracellular succinoglycan degrading activities and for production of low-molecular-weight succinoglycan by R. meliloti. Based on these results, we propose that ExsH is a succinoglycan depolymerase secreted by a Type I secretion system composed of PrsD and PrsE, and that the ExsH and ExoK glycanases contribute to production of low-molecular-weight succinoglycan.

ATP-Binding Cassette Transporters↗

PubMed2006

Type II secretion: from structure to function.

Gram-negative bacteria use the type II secretion system to transport a large number of secreted proteins from the periplasmic space into the extracellular environment. Many of the secreted proteins are major virulence factors in plants and animals. The components of the type II secretion system are located in both the inner and outer membranes where they assemble into a multi-protein, cell-envelope spanning, complex. This review discusses recent progress, particularly newly published structures obtained by X-ray crystallography and electron microscopy that have increased our understanding of how the type II secretion apparatus functions and the role that individual proteins play in this complex system.

Bacterial Outer Membrane Proteins↗

PubMed2004

Euroconference on the Biology of Type IV Secretion Processes: bacterial gates into the outer world.

Type IV secretion systems (T4SSs) mediate both protein and ssDNA secretion from a wide range of bacteria into virtually any cell type or into the milieu. It is this versatility that confers on them the ability to participate in many processes of bacterial life that imply communication with their environment. Type IV secretion systems are involved in horizontal DNA transfer to other bacteria and to plant cells, in DNA uptake from the milieu, in toxin secretion into the milieu, and in the injection of virulence factors into the eukaryotic host cell in a number of mammalian and plant pathogens. Recently, a EuroConference addressed the different aspects of the biology of these transmembrane multiprotein complexes, from the crystal structure of the individual components to the modification that the secreted substrates induce in the recipient cell. Significant progress has been made in the understanding of the molecular architecture and mechanism of secretion. The analysis of protein-protein interactions confirms the role of coupling proteins as substrate recruiters for the transporter. The VirB10 component of the complex has come up as a strong candidate for signal transducer. The wide range of effects on the recipient suggests that many effector proteins are secreted. New effector proteins are being identified for both plant and animal pathogens, as are their targets within the host cells. New T4SS members are being identified that perform novel roles, beyond DNA transfer and virulence, such as establishment of symbiotic processes. Our current knowledge of the Biology of Type IV Secretion Processes increases our ability to exploit them as biotechnological tools or to use them as new targets for inhibitors that could constitute a new generation of antimicrobials in the near future.

Animals↗

PubMed2000

The gene coding for the Hrp pilus structural protein is required for type III secretion of Hrp and Avr proteins in Pseudomonas syringae pv. tomato.

Bacterial surface appendages called pili often are associated with DNA and/or protein transfer between cells. The exact function of pili in the transfer process is not understood and is a matter of considerable debate. The Hrp pilus is assembled by the Hrp type III protein secretion system of Pseudomonas syringae pv. tomato (Pst) strain DC3000. In this study, we show that the hrpA gene, which encodes the major subunit of the Hrp pilus, is required for secretion of putative virulence proteins, such as HrpW and AvrPto. In addition, the hrpA gene is required for full expression of genes that encode regulatory, secretion, and effector proteins of the type III secretion system. hrpA-mediated gene regulation apparently is through effect on the mRNA level of two previously characterized regulatory genes, hrpR and hrpS. Ectopic expression of the hrpRS gene operon restored gene expression, but not protein secretion, in the hrpA mutant. Three single amino acid mutations at the HrpA carboxyl terminus were identified that affect the secretion or regulatory function of the HrpA protein. These results define an essential role of the Hrp pilus structural gene in protein secretion and coordinate regulation of the type III secretion system in Pst DC3000.

Amino Acids↗