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  • 1
    Online Resource
    Online Resource
    Human Immunodeficiency Virus-Specific CD8 + T-Cell Responses Do Not Predict Viral Growth and Clearance Rates during Structured Intermittent Antiretroviral Therapy
    American Society for Microbiology ; 2002
    In:  Journal of Virology Vol. 76, No. 20 ( 2002-10-15), p. 10169-10176
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 76, No. 20 ( 2002-10-15), p. 10169-10176
    Abstract: There is a continuing search for better ways to use existing drugs against human immunodeficiency virus (HIV). One idea is to use short therapy interruptions to “autovaccinate” HIV-infected patients. A group of 13 chronically HIV-infected patients enrolled in a trial of such so-called structured treatment interruptions (STIs) were intensively studied with respect to their viral load (VL) and HIV-specific CD8 + T-cell (cytotoxic T-lymphocyte [CTL]) responses. We found that 10 of the 13 patients had plateau VLs after STIs that were lower than their pretreatment VLs. While viral rebound rates became lower over STIs, there were no changes in clearance rates. Although numbers of CTLs did increase over the same time that viral rebounds decreased, there was no correlation between CTL count and either viral rebound rates or clearance rates. Finally, we asked whether absolute numbers of or changes in numbers of CTLs predict plateau VLs after STIs. No measure of CTLs was able to predict plateau VLs. Thus, there was no signature in these data of an important contribution to virological control from HIV-specific CD8 + T lymphocytes.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.76.20.10169-10176.2002
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2002
    detail.hit.zdb_id: 1495529-5
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  • 2
    Online Resource
    Online Resource
    Outer Membrane Targeting of Passenger Proteins by the Vacuolating Cytotoxin Autotransporter of Helicobacter pylori
    American Society for Microbiology ; 2001
    In:  Infection and Immunity Vol. 69, No. 11 ( 2001-11), p. 6769-6775
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 69, No. 11 ( 2001-11), p. 6769-6775
    Abstract: Helicobacter pylori produces a number of proteins associated with the outer membrane, including adhesins and the vacuolating cytotoxin. These proteins are supposed to integrate into the outer membrane by β-barrel structures, characteristic of the family of autotransporter proteins. By using the SOMPES (shuttle vector-based outer membrane protein expression) system for outer membrane protein production, we were able to functionally express in H. pylori the cholera toxin B subunit genetically fused to the C-terminal VacA domain. We demonstrate that the fusion protein is translocated to the H. pylori outer membrane and that the CtxB domain is exposed on the H. pylori surface. Thus, we provide the first experimental evidence that the C-terminal β-domain of VacA can transport a foreign passenger protein to the H. pylori surface and hence acts as a functional autotransporter.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/IAI.69.11.6769-6775.2001
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2001
    detail.hit.zdb_id: 1483247-1
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  • 3
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    Online Resource
    A Dominant Role for Extracellular Glutathione S -Transferase from Onchocerca volvulus Is the Production of Prostaglandin D 2
    American Society for Microbiology ; 2003
    In:  Infection and Immunity Vol. 71, No. 6 ( 2003-06), p. 3603-3606
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 71, No. 6 ( 2003-06), p. 3603-3606
    Abstract: The extracellular glutathione S -transferase from the filarial parasite Onchocerca volvulus ( Ov -GST1) is a glutathione-dependent prostaglandin D synthase. Ov -GST1, located in the outer hypodermal lamellae and in parts of the cuticle, produces prostaglandin D 2 directly at the parasite-host interface. Ov -GST1 therefore has the potential to participate in the modulation of the host immune response by contributing to the production of prostanoids; this supports the predominant hypothesis that parasite-derived eicosanoids influence host inflammatory and immune cells.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/IAI.71.6.3603-3606.2003
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2003
    detail.hit.zdb_id: 1483247-1
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  • 4
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    Online Resource
    Simple and Portable Magnetic Immunoassay for Rapid Detection and Sensitive Quantification of Plant Viruses
    American Society for Microbiology ; 2015
    In:  Applied and Environmental Microbiology Vol. 81, No. 9 ( 2015-05), p. 3039-3048
    Details
    In: Applied and Environmental Microbiology, American Society for Microbiology, Vol. 81, No. 9 ( 2015-05), p. 3039-3048
    Abstract: Plant pathogens cause major economic losses in the agricultural industry because late detection delays the implementation of measures that can prevent their dissemination. Sensitive and robust procedures for the rapid detection of plant pathogens are therefore required to reduce yield losses and the use of expensive, environmentally damaging chemicals. Here we describe a simple and portable system for the rapid detection of viral pathogens in infected plants based on immunofiltration, subsequent magnetic detection, and the quantification of magnetically labeled virus particles. Grapevine fanleaf virus (GFLV) was chosen as a model pathogen. Monoclonal antibodies recognizing the GFLV capsid protein were immobilized onto immunofiltration columns, and the same antibodies were linked to magnetic nanoparticles. GFLV was quantified by immunofiltration with magnetic labeling in a double-antibody sandwich configuration. A magnetic frequency mixing technique, in which a two-frequency magnetic excitation field was used to induce a sum frequency signal in the resonant detection coil, corresponding to the virus concentration within the immunofiltration column, was used for high-sensitivity quantification. We were able to measure GFLV concentrations in the range of 6 ng/ml to 20 μg/ml in less than 30 min. The magnetic immunoassay could also be adapted to detect other plant viruses, including Potato virus X and Tobacco mosaic virus , with detection limits of 2 to 60 ng/ml.
    Type of Medium: Online Resource
    ISSN: 0099-2240 , 1098-5336
    URL: Article
    DOI: 10.1128/AEM.03667-14
    RVK:
    WA 15000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2015
    detail.hit.zdb_id: 223011-2
    detail.hit.zdb_id: 1478346-0
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    The RecA Protein of Helicobacter pylori Requires a Posttranslational Modification for Full Activity
    American Society for Microbiology ; 2004
    In:  Journal of Bacteriology Vol. 186, No. 3 ( 2004-02), p. 777-784
    Details
    In: Journal of Bacteriology, American Society for Microbiology, Vol. 186, No. 3 ( 2004-02), p. 777-784
    Abstract: The RecA protein is a central component of the homologous recombination machinery and of the SOS system in most bacteria. In performing these functions, it is involved in DNA repair processes and plays an important role in natural transformation competence. This may be especially important in Helicobacter pylori , where an unusually high degree of microdiversity among strains is generated by homologous recombination. We have suggested previously that the H. pylori RecA protein is subject to posttranslational modifications that result in a slight shift in its electrophoretic mobility. Here we show that at least two genes downstream of recA are involved in this modification and that this process is dependent on genes involved in glycosylation and lipopolysaccharide biosynthesis. Site-directed mutagenesis of a putative glycosylation site results in production of an unmodified RecA protein. This posttranslational modification is not involved in membrane targeting or cell division functions but is necessary for the full function of RecA in DNA repair. Thus, it might be an adaptation to the specific requirements of H. pylori in its natural environment.
    Type of Medium: Online Resource
    ISSN: 0021-9193 , 1098-5530
    URL: Article
    DOI: 10.1128/JB.186.3.777-784.2004
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2004
    detail.hit.zdb_id: 1481988-0
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Fungal Melanin Biosynthesis Pathway as Source for Fungal Toxins
    American Society for Microbiology ; 2022
    In:  mBio Vol. 13, No. 3 ( 2022-06-28)
    Details
    In: mBio, American Society for Microbiology, Vol. 13, No. 3 ( 2022-06-28)
    Abstract: Contamination of food and feed with toxin-producing fungi is a major threat in agriculture and for human health. The filamentous fungus Alternaria alternata is one of the most widespread postharvest contaminants and a weak plant pathogen. It produces a large variety of secondary metabolites with alternariol and its derivatives as characteristic mycotoxin. Other important phyto- and mycotoxins are perylene quinones (PQs), some of which have anticancer properties. Here, we discovered that the PQ altertoxin (ATX) biosynthesis shares most enzymes with the 1,8-dihydroxynaphthalene (1,8-DHN) melanin pathway. However, melanin was formed in aerial hyphae and spores, and ATXs were synthesized in substrate hyphae. This spatial separation is achieved through the promiscuity of a polyketide synthase, presumably producing a pentaketide (T4HN), a hexaketide (AT4HN), and a heptaketide (YWA1) as products. T4HN directly enters the altertoxin and DHN melanin pathway, whereas AT4HN and YWA1 can be converted only in aerial hyphae, which probably leads to a higher T4HN concentration, favoring 1,8-DHN melanin formation. Whereas the production of ATXs was strictly dependent on the CmrA transcription factor, melanin could still be produced in the absence of CmrA to some extent. This suggests that different cues regulate melanin and toxin formation. Since DHN melanin is produced by many fungi, PQs or related compounds may be produced in many more fungi than so far assumed. IMPORTANCE Mycotoxins are a major threat for human health. Food safety control relies on the identification of the toxins or the detection of the expression of the respective genes. The latter method, however, relies on the knowledge of the biosynthetic pathway and the key genes. Alternaria alternata is a major food contaminant and produces many different mycotoxins with altertoxins and other perylene quinones as prominent examples. Here, we discovered that the biosynthetic pathway for altertoxins shares most of the enzymes with the dihydroxynaphthalene (DHN) melanin pathway. Because the DHN melanin pathway is widespread among fungi, the production of mycotoxins of the perylene quinone class could be more widespread than so far anticipated.
    Type of Medium: Online Resource
    ISSN: 2150-7511
    URL: Article
    DOI: 10.1128/mbio.00219-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2557172-2
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  • 7
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    Online Resource
    In Vivo and In Vitro Escape from Neutralizing Antibodies 2G12, 2F5, and 4E10
    American Society for Microbiology ; 2007
    In:  Journal of Virology Vol. 81, No. 16 ( 2007-08-15), p. 8793-8808
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 81, No. 16 ( 2007-08-15), p. 8793-8808
    Abstract: Recently, passive immunization of human immunodeficiency virus (HIV)-infected individuals with monoclonal antibodies (MAbs) 2G12, 2F5, and 4E10 provided evidence of the in vivo activity of 2G12 but raised concerns about the function of the two membrane-proximal external region (MPER)-specific MAbs (A. Trkola, H. Kuster, P. Rusert, B. Joos, M. Fischer, C. Leemann, A. Manrique, M. Huber, M. Rehr, A. Oxenius, R. Weber, G. Stiegler, B. Vcelar, H. Katinger, L. Aceto, and H. F. Gunthard, Nat. Med. 11:615-622, 2005). In the light of MPER-targeting vaccines under development, we performed an in-depth analysis of the emergence of mutations conferring resistance to these three MAbs to further elucidate their activity. Clonal analysis of the MPER of plasma virus samples derived during antibody treatment confirmed that no changes in this region had occurred in vivo. Sequence analysis of the 2G12 epitope relevant N-glycosylation sites of viruses derived from 13 patients during the trial supported the phenotypic evaluation, demonstrating that mutations in these sites are associated with resistance. In vitro selection experiments with isolates of four of these individuals corroborated the in vivo finding that virus strains rapidly escape 2G12 pressure. Notably, in vitro resistance mutations differed, in most cases, from those found in vivo. Importantly, in vitro selection with 2F5 and 4E10 demonstrated that resistance to these MAbs can be difficult to achieve and can lead to selection of variants with impaired infectivity. This remarkable vulnerability of the virus to interference within the MPER calls for a further evaluation of the safety and efficacy of MPER-targeting therapeutic and vaccination strategies.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.00598-07
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2007
    detail.hit.zdb_id: 1495529-5
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  • 8
    Online Resource
    Online Resource
    The Structure of the Dizinc Subclass B2 Metallo-β-Lactamase CphA Reveals that the Second Inhibitory Zinc Ion Binds in the Histidine Site
    American Society for Microbiology ; 2009
    In:  Antimicrobial Agents and Chemotherapy Vol. 53, No. 10 ( 2009-10), p. 4464-4471
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 53, No. 10 ( 2009-10), p. 4464-4471
    Abstract: Bacteria can defend themselves against β-lactam antibiotics through the expression of class B β-lactamases, which cleave the β-lactam amide bond and render the molecule harmless. There are three subclasses of class B β-lactamases (B1, B2, and B3), all of which require Zn 2+ for activity and can bind either one or two zinc ions. Whereas the B1 and B3 metallo-β-lactamases are most active as dizinc enzymes, subclass B2 enzymes, such as Aeromonas hydrophila CphA, are inhibited by the binding of a second zinc ion. We crystallized A. hydrophila CphA in order to determine the binding site of the inhibitory zinc ion. X-ray data from zinc-saturated crystals allowed us to solve the crystal structures of the dizinc forms of the wild-type enzyme and N220G mutant. The first zinc ion binds in the cysteine site, as previously determined for the monozinc form of the enzyme. The second zinc ion occupies a slightly modified histidine site, where the conserved His118 and His196 residues act as metal ligands. This atypical coordination sphere probably explains the rather high dissociation constant for the second zinc ion compared to those observed with enzymes of subclasses B1 and B3. Inhibition by the second zinc ion results from immobilization of the catalytically important His118 and His196 residues, as well as the folding of the Gly232-Asn233 loop into a position that covers the active site.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00288-09
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2009
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 9
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    Online Resource
    Fatal Myocarditis Associated with Acute Parvovirus B19 and Human Herpesvirus 6 Coinfection
    American Society for Microbiology ; 2001
    In:  Journal of Clinical Microbiology Vol. 39, No. 12 ( 2001-12), p. 4585-4587
    Details
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 39, No. 12 ( 2001-12), p. 4585-4587
    Abstract: We report on the case of a healthy young boy who developed a fulminant myocarditis due to acute coinfection with erythrovirus (parvovirus B19) and human herpesvirus 6 (HHV-6) in the absence of an antiviral immune response. We suggest that the HHV-6-induced immunosuppression enhanced dissemination of parvovirus B19, which led to fatal myocarditis.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    URL: Article
    DOI: 10.1128/JCM.39.12.4585-4587.2001
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2001
    detail.hit.zdb_id: 1498353-9
    SSG: 12
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  • 10
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    Online Resource
    Functional and Topological Characterization of Novel Components of the comB DNA Transformation Competence System in Helicobacter pylori
    American Society for Microbiology ; 2006
    In:  Journal of Bacteriology Vol. 188, No. 3 ( 2006-02), p. 882-893
    Details
    In: Journal of Bacteriology, American Society for Microbiology, Vol. 188, No. 3 ( 2006-02), p. 882-893
    Abstract: Helicobacter pylori is one of the most diverse bacterial species known. A rational basis for this genetic variation may be provided by its natural competence for genetic transformation and high-frequency recombination. Many bacterial competence systems have homology with proteins that are involved in the assembly of type IV pili and type II secretion systems. In H. pylori , DNA uptake relies on a transport system related to type IV secretion systems (T4SS) designated the comB system. The prototype of a T4SS in Agrobacterium tumefaciens consists of 11 VirB proteins and VirD4, which form the core unit necessary for the delivery of single proteins or large nucleoprotein complexes into target cells. In the past we identified proteins ComB4 and ComB7 through ComB10 as being involved in the process of DNA uptake in H. pylori . In this study we identified and functionally characterized further (T4SS-homologous) components of the comB transformation competence system. By combining computer prediction modeling, experimental topology determination, generation of knockout strains, and genetic complementation studies we identified ComB2, ComB3, and ComB6 as essential components of the transformation apparatus, structurally and functionally homologous to VirB2, VirB3, and VirB6, respectively. comB2 , comB3 , and comB4 are organized as a separate operon. Thus, for the H. pylori comB system, all T4SS core components have been identified except for homologues to VirB1, VirD4, VirB5, and VirB11.
    Type of Medium: Online Resource
    ISSN: 0021-9193 , 1098-5530
    URL: Article
    DOI: 10.1128/JB.188.3.882-893.2006
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2006
    detail.hit.zdb_id: 1481988-0
    SSG: 12
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