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  • 1
    Electronic Resource
    Electronic Resource
    Antigenic variation of pilin regulates adhesion of Neisseria meningitidis to human epithelial cells (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Molecular microbiology 8 (1993), S. 0 
    Details
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Pili have been shown to play an essential role in the adhesion of Neisseria meningitidis to epithelial cells. However, among piliated strains, both inter- and intrastrain variability exist with respect to their degree of adhesion to epithelial cells in vitro (Virji et al., 1992). This suggests that factors other than the presence of pili per se are involved in this process. The N. meningitidis pilin subunit undergoes extensive antigenic variation. Piliated low- and high-adhesive derivatives of the same N. meningitidis strain were selected and the nucleotide sequence of the pilin gene expressed in each was determined. The highly adhesive derivatives had the same pilin sequence. The alleles encoding the pilin subunit of the low-adhesive derivatives were completely different from the one found in the high-adhesive isolates. Using polyclonal antibodies raised against one hyperadhesive variant, it was confirmed that the low-adhesive piliated derivatives expressed pilin variants antigenically different from the highly adhesive strains. The role of antigenic variation in the adhesive process of N. meningitidis was confirmed by performing allelic exchanges of the pilE locus between low-and high-adhesive isolates. Antigenic variation has been considered a means by which virulent bacteria evade the host immune system. This work provides genetic proof that a bacterial pathogen, N. meningitidis, can use antigenic variation to modulate their degree of virulence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2958.1993.tb01615.x
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  • 2
    Electronic Resource
    Electronic Resource
    Neisseria meningitidis accelerates ferritin degradation in host epithelial cells to yield an essential iron source (2004)
    Oxford, UK : Blackwell Science Ltd
    Molecular microbiology 53 (2004), S. 0 
    Details
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: In order to colonize humans and cause disease, pathogenic bacteria must assimilate iron from their host. The vast majority of non-haem iron in humans is localized intracellularly, within the storage molecule ferritin. Despite the vast reserves of iron within ferritin, no pathogen has been demonstrated previously to exploit this molecule as an iron source. Here, we show that the Gram-negative diplococcus Neisseria meningitidis can trigger rapid redistribution and degradation of cytosolic ferritin within infected epithelial cells. Indirect immunofluorescence microscopy revealed that cytosolic ferritin is aggregated and recruited to intracellular meningococci (MC). The half-life of ferritin within cultured epithelial cells was found to decrease from 20.1 to 5.3 h upon infection with MC. Supplementation of infected epithelial cells with ascorbic acid abolished ferritin redistribution and degradation and prevented intracellular MC from replicating. The lysosomal protease inhibitor leupeptin slowed ferritin turnover and also retarded MC replication. Our laboratory has shown recently that MC can interfere with transferrin uptake by infected cells (Bonnah R.A., et al., 2000, Cell Microbiol 2: 207–218) and that, perhaps as a result, the infected cells have a transcriptional profile indicative of iron starvation (Bonnah, R.A., et al., 2004, Cell Microbiol 6: 473–484). In view of these findings, we suggest that accelerated ferritin degradation occurs as a response to an iron starvation state induced by MC infection and that ferritin degradation provides intracellular MC with a critical source of iron.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2958.2004.04169.x
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  • 3
    Electronic Resource
    Electronic Resource
    Cloning and characterization of the Neisseria meningitidis rfaC gene encoding α-1,5 heptosyltransferase I (1997)
    Oxford, UK : Blackwell Publishing Ltd
    FEMS microbiology letters 151 (1997), S. 0 
    Details
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: We cloned and characterized the Neisseria meningitidis rfaC gene which encodes an enzyme, α-1,5 heptosyltransferase I, involved in the synthesis of the deep-core of the lipooligosaccharide. The N. meningitidis rfaC mutant, obtained by an allelic exchange, produced lipooligosaccharide which migrated faster in sodium dodecyl sulfate-polyacrylamide gel electrophoresis than the lipooligosaccharide isolated from the wild-type N. meningitidis. The N. meningitidis rfaC mutant was not affected by growth in a rich microbiological medium and did not show any defect in adhesion to epithelial cell lines. Conversely, the rfaC mutant was attenuated in the infant rat model of meningococcemia, thus confirming the importance of intact lipooligosaccharide in the virulence of N. meningitidis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1574-6968.1997.tb10392.x
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  • 4
    Electronic Resource
    Electronic Resource
    Pilus retraction powers bacterial twitching motility (2000)
    [s.l.] : Macmillian Magazines Ltd.
    Nature 407 (2000), S. 98-102 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Twitching and social gliding motility allow many Gram negative bacteria to crawl along surfaces, and are implicated in a wide range of biological functions. Type IV pili (Tfp) are required for twitching and social gliding, but the mechanism by which these filaments promote motility has ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/35024105
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  • 5
    Electronic Resource
    Electronic Resource
    INTERACTIONS OF PATHOGENIC NEISSERIAE WITH EPITHELIAL CELL MEMBRANES (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 16 (2000), S. 423-457 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The closely related bacterial pathogens Neisseria gonorrhoeae (gonococci, GC) and N. meningitidis (meningococci, MC) initiate infection at human mucosal epithelia. Colonization begins at apical epithelial surfaces with a multistep adhesion cascade, followed by invasion of the host cell, intracellular persistence, transcytosis, and exit. These activities are modulated by the interaction of a panoply of virulence factors with their cognate host cell receptors, and signals are sent from pathogen to host and host to pathogen at multiple stages of the adhesion cascade. Recent advances place us on the verge of understanding the colonization process at a molecular level of detail. In this review we describe the Neisseria virulence factors in the context of epithelial cell biology, placing special emphasis on the signaling functions of type IV pili, pilus-based twitching motility, and the Opa and Opc outermembrane adhesin/invasin proteins. We also summarize what is known about bacterial intracellular trafficking and growth. With the accelerated integration of tools from cell biology, biochemistry, biophysics, and genomics, experimentation in the next few years should bring unprecedented insights into the interactions of Neisseriae with their host.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.16.1.423
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  • 6
    Electronic Resource
    Electronic Resource
    The Neisseria meningitidis haemoglobin receptor: its role in iron utilization and virulence (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Molecular microbiology 15 (1995), S. 0 
    Details
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The Neisseris meningitidis haemoglobin receptor gene, hmbR, was cloned by complementation in a porphyrin-requiring Escherichia coli mutant. hmbR encodes an 89.5 kDa outer membrane protein which shares amino acid homology with the TonB-dependent receptors of Gram-negative bacteria. HmbR had the highest similarity to Neisseria transferrin and lactoferrin receptors. The utilization of haemoglobin as an iron source required internalization of the haemin moiety by the cell. The mechanism of haemin internalization via the haemoglobin receptor was TonB-dependent in E. coli. A N. meningitidis hmbR mutant was unable to use haemoglobin but could still use haemin as a sole iron source. The existence of a second N. meningitidis receptor gene, specific for haemin, was shown by the isolation of cosmids which did not hybridize with the hmbR probe, but which were able to complement an E. coli hemA aroB mutant on haemin-supplemented plates. The N. meningitidis hmbR mutant was attenuated in an infant rat model for meningococcal infection, indicating that haemoglobin utilization is important for N. meningitidis virulence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2958.1995.tb02266.x
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  • 7
    Electronic Resource
    Electronic Resource
    The opaH locus of Neisseria gonorrhoeae MS11A is involved in epithelial cell invasion (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Molecular microbiology 13 (1994), S. 0 
    Details
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: In order to produce a successful infection, Neisseria gonorrhoeae (GC) must attach to and invade mucosal epithelial cells. To identify GC gene products involved in this early interaction with host cells we constructed a gene bank derived from a clinical isolate of GC, and isolated a clone which had the capacity to adhere to the human endometrial adenocarcinoma tissue-culture line HEC-1-B. The cloned sequence was identified as a member of the opa gene family whose protein products have been associated with virulence. The GC chromosome contains numerous variant opa genes which, in MS11, are designated opaA-K. Previous work showed that expression of opaC confers a highly invasive phenotype upon strain MS11. When our cloned opa gene was mutated and returned to the GC MS11A chromosome by transformation and homologous recombination, we isolated one transformation that was significantly reduced in its invasive capacity. The locus mutated in this transformant was identified as opaH. Our resuits indicate that invasive-ness of GC for human epithelail cells can be determined by more than one opa gene in strain MS11 A.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2958.1994.tb00483.x
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  • 8
    Electronic Resource
    Electronic Resource
    Identification of a novel large extrachromosomal DNA (LED) in the Trypanosomatidae (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Molecular microbiology 6 (1992), S. 0 
    Details
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: We have identified a novel 75 kbp large extrachromosomal DNA (LED) which is stably maintained during developmental conversion of Trypanosoma cruzi. It has a covalently closed circular conformation and is not derived from the kinetoplast network. In all T. cruzi strains analysed, LED contains 18S rRNA and spliced leader (sl) sequences. LED from the T. cruzi Y strain contains a minimum of 15 copies of the sl repeat arrayed in a head-to-tail configuration and 50 copies of a 196 bp repeat. LED is also present in Trypanosoma dionisii (subgenus Schizotrypanosoma) and in other members of the family Trypanosomatidae. LED from different T. cruzi strains and from other members of the Trypanosomatidae differ in their content of large ribosomal subunit rRNA sequences and the 196 bp repeat. The presence of LED in four evolutionarily distant trypanosomatid species suggests that it plays an important rote in the biology of these parasites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2958.1992.tb01405.x
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  • 9
    Electronic Resource
    Electronic Resource
    Type IV pili of pathogenic Neisseriae elicit cortical plaque formation in epithelial cells (1999)
    Oxford BSL : Blackwell Science Ltd
    Molecular microbiology 32 (1999), S. 0 
    Details
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The pathogenic Neisseriae Neisseria meningitidis and Neisseria gonorrhoeae, initiate colonization by attaching to host cells using type IV pili. Subsequent adhesive interactions are mediated through the binding of other bacterial adhesins, in particular the Opa family of outer membrane proteins. Here, we have shown that pilus-mediated adhesion to host cells by either meningococci or gonococci triggers the rapid, localized formation of dramatic cortical plaques in host epithelial cells. Cortical plaques are enriched in both components of the cortical cytoskeleton and a subset of integral membrane proteins. These include: CD44v3, a heparan sulphate proteoglycan that may serve as an Opa receptor; EGFR, a receptor tyrosine kinase; CD44 and ICAM-1, adhesion molecules known to mediate inflammatory responses; f-actin; and ezrin, a component that tethers membrane components to the actin cytoskeleton. Genetic analyses reveal that cortical plaque formation is highly adhesin specific. Both pilE and pilC null mutants fail to induce cortical plaques, indicating that neisserial type IV pili are required for cortical plaque induction. Mutations in pilT, a gene required for pilus-mediated twitching motility, confer a partial defect in cortical plaque formation. In contrast to type IV pili, many other neisserial surface structures are not involved in cortical plaque induction, including Opa, Opc, glycolipid GgO4-binding adhesins, polysialic acid capsule or a particular lipooligosaccharide variant. Furthermore, it is shown that type IV pili allow gonococci to overcome the inhibitory effect of heparin, a soluble receptor analogue, on gonococcal invasion of Chang and A431 epithelial cells. These and other observations strongly suggest that type IV pili play an active role in initiating neisserial infection of the mucosal surface in vivo. The functions of type IV pili and other neisserial adhesins are discussed in the specific context of the mucosal microenvironment, and a multistep model for neisserial colonization of mucosal epithelia is proposed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2958.1999.01459.x
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  • 10
    Electronic Resource
    Electronic Resource
    Recombination-deficient mutants of Salmonella typhimurium are avirulent and sensitive to the oxidative burst of macrophages (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Molecular microbiology 7 (1993), S. 0 
    Details
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Mutations in the genes recA and recBC were constructed in the virulent Salmonella typhimurium strain 14028s. Both the recA and recBC mutants were attenuated in mice. The mutants were also sensitive to killing by macrophages in vitro. The recombination mutants were no longer macrophage sensitive in a variant line of J774 macrophage-like cells that fail to generate superoxide. This suggests that repair of DNA damage by Salmonella is necessary for full virulence in vivo and that the oxidative burst of phagocytes is one source of such DNA damage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2958.1993.tb01184.x
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