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J Heesemann

Publications and source records attributed to J Heesemann.

At least 145 records · Page 8Linked to original sources
PubMed1994

Early gamma interferon mRNA expression is associated with resistance of mice against Yersinia enterocolitica.

T cells in cooperation with macrophages play an important role in resolution of primary Yersinia enterocolitica infection in mice. Previous work from this laboratory demonstrated that gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) are essential mediators of these processes. In an attempt to elucidate early mechanisms of resistance, we investigated cytokine mRNA production, including that for interleukin-1 beta (IL-1 beta), IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma, after primary as well as secondary Y. enterocolitica infection in Yersinia-susceptible BALB/c mice and Yersinia-resistant C57BL/6 mice. In both strains of mice, proinflammatory cytokines such as IL-1 beta, IL-6, and TNF-alpha were expressed rapidly and to comparable degrees, while IFN-gamma expression was enhanced two- to eightfold in C57BL/6 mice, as revealed by semiquantitative reverse transcription PCR. Similar results were found in both mouse strains after secondary Y. enterocolitica infection. IL-2 mRNA was detected only during secondary infection and disappeared rapidly in BALB/c mice. IL-4 mRNA expression was detectable in C57BL/6 but not BALB/c mice. The levels of cytokine mRNA expression correlated closely with the number of injected bacteria. The findings reported here support the hypothesis that early and enhanced production of IFN-gamma may be associated with a state of heightened resistance against Y. enterocolitica infection.

Animals↗
PubMed1994

Characterization of transposon mutants of biofilm-producing Staphylococcus epidermidis impaired in the accumulative phase of biofilm production: genetic identification of a hexosamine-containing polysaccharide intercellular adhesin.

The primary attachment to polymer surfaces followed by accumulation in multilayered cell clusters leads to production of Staphylococcus epidermidis biofilms, which are thought to contribute to virulence in biomaterial-related infections. We isolated Tn917 transposon mutants of biofilm-producing S. epidermidis 13-1, which were completely biofilm negative. In pulsed-field gel electrophoresis no obvious deletions of the mutants were noted. The Tn917 insertions of mutants M10 and M11 were located on different EcoRI fragments but on identical 60-kb SmaI and 17-kb BamHI chromosomal fragments. Linkage of transposon insertions of mutants M10 and M11 with the altered phenotype was demonstrated by phage transduction, whereas the several other mutants apparently represented spontaneous variants. In a primary attachment assay with polystyrene spheres, no significant difference between any of the mutants and the wild type could be detected. Cell clustering as an indication of intercellular adhesion, which is a prerequisite for accumulation in multilayered cell clusters, was not detected with any mutant. These results demonstrate that the mutants were impaired in the accumulative phase of biofilm production. Mutants M10 and M11 did not produce detectable amounts of a specific polysaccharide antigen (D. Mack, N. Siemssen, and R. Laufs, Infect. Immun. 60:2048-2057, 1992), whereas substantially reduced amounts of antigen were produced by the spontaneous variants. Hexosamine was determined as the major specific component of the antigen enriched by gel filtration of biofilm-producing S. epidermidis 1457 because almost no hexosamine was detected in material prepared from the isogenic biofilm-negative transductant 1457-M11, which differentiates the antigen from other S. epidermidis polysaccharide components. Our results provide direct genetic evidence for a function of the antigen in the accumulative phase of biofilm production by S. epidermidis by mediating intercellular adhesion.

Antigens, Bacterial↗
PubMed1994

Yersinia-specific antibodies in serum and synovial fluid in patients with Yersinia triggered reactive arthritis.

OBJECTIVES: To further evaluate the role of bacterial antigens in triggering inflammation in the joint in patients with reactive arthritis by studying local antibody synthesis in the joint. METHODS: Yersinia-specific antibodies in paired serum and synovial fluid samples from 29 patients with yersinia triggered reactive arthritis were studied using an enzyme linked immunosorbent assay (ELISA), an inhibition ELISA with six monoclonal antibodies against lipopolysaccharide or released proteins of yersinia and immunoblotting. Antibodies of IgM, IgG and IgA classes, as well as antibodies of IgA subclasses and those containing secretory component were measured against the lipopolysaccharide and the sodium dodecyl sulphate extract of whole Yersinia enterocolitica O:3 bacteria. RESULTS: It was shown that yersinia-specific antibodies, as well as antibodies against other microbial antigens (rubella, measles, Bordetella pertussis, tetanus toxoid and Candida albicans) in synovial fluid mirror those in serum by concentration, by specificity and by distribution in classes and subclasses. CONCLUSION: These results do not suggest any strong local antibody production, but indicate that the majority of yersinia antibodies in the synovial fluid are derived from the circulation.

Adolescent↗
PubMed1994

[The effect of the pipe material of the drinking water system on the frequency of Legionella in a hospital].

In this paper the prevalence of Legionella in water samples from cold and warm water supply systems made of copper, iron and polyethylene was determined. Water supplied by copper pipes revealed to be nearly free of Legionella (only 2% of probes positive), but water from iron (90%) or polyethylene pipes (65% probes positive) proved to be heavily contaminated. The 82 isolates were identified as Legionella pneumophila, one from serogroup 1, the others from serogroup 4.

Colony Count, Microbial↗
PubMed1994

[Detection by molecular biology techniques of diphtheria toxin production in corynebacteria].

The ability to secrete a potent protein-toxin called diphtheria toxin (DT) is of outstanding importance for the outcome of diphtheria epidemics. Rapid molecular-biological screening methods are shown that can improve the differentiation between toxinogenic and non-toxinogenic Corynebacterium diphtheriae strains. The recently reported infection with an endemic, putative toxinogenic Corynebacterium diphtheriae strain in Lower Saxony is discussed.

Corynebacterium diphtheriae↗
PubMed1994

Idiotype identity in a MALT-type lymphoma and B cells in Helicobacter pylori associated chronic gastritis.

BACKGROUND: To investigate the mechanisms triggering MALT-lymphoma development, we examined the occurrence of normal B cells in lymphoid tissue and chronic gastritis with the same idiotype as an IgA-positive MALT lymphoma. EXPERIMENTAL DESIGN: Lymphoma idiotype IgA was produced by monoclonal human antibody technology. Against this idiotype a murine monoclonal antibody 27/165 with anti-idiotypic (alpha Id) specificities was raised, and applied immunohistochemically to identify the non-neoplastic precursor B cells in non-neoplastic human tissues. RESULTS: alpha Id 27/165 reacted exclusively with the IgA expressing MALT lymphoma but not with 20 other MALT-type gastric lymphomas nor with 26 nodal lymphomas and was not reactive with normal and inflamed lymph nodes. alpha Id 27/165 immunoreactivity was also absent from MALT of different mucosal sites but was readily encountered on a substantial number of lymphocytes and plasma cells in 95% cases of chronic gastritis associated with Helicobacter pylori (H.p.). The target antigen of the lymphoma IgA was found to be a common antigen of IgA and IgM plasma cells of MALT but not a constituent of bacteria commonly involved in the pathogenesis of gastritis. CONCLUSIONS: The distinct binding of alpha Id 27/165 to only reactive mucosal B cells is a first direct evidence for the evolution of MALT-type lymphoma from chronic gastritis. Since the target antigen of the lymphoma IgA has been found to be an autoantigen of MALT plasma cells it is suggested that this MALT-type lymphoma may have arisen after triggering by an autoimmune response resulting from H.p.-induced gastritis.

Antibodies, Monoclonal↗
PubMed1993

The spectrum of immune responses to Campylobacter jejuni and glycoconjugates in Guillain-Barré syndrome and in other neuroimmunological disorders.

An acute infectious illness frequently precedes the Guillain-Barré syndrome. Recently, Campylobacter jejuni was claimed to be a predominant precipitating agent that may also trigger a humoral immune response to glycoconjugates of peripheral myelin in Guillain-Barré syndrome. Because of conflicting reports, we determined the frequency of a recent infection with C. jejuni in 38 patients with Guillain-Barré syndrome using a highly sensitive and specific immunoblot technique, and of the presence of circulating antibodies to gangliosides. We detected IgM and/or IgG C. jejuni directed antibodies in 15 of 38 patients with Guillain-Barré syndrome. In contrast, only 7 of 39 healthy control subjects, 3 of 20 patients with multiple sclerosis, and 2 of 72 patients with neuroborreliosis showed IgA or IgM antibody responses to C. jejuni. In Guillain-Barré syndrome, C. jejuni-specific antibodies were predominantly directed to outer membrane proteins of one specific serotype, Lior 11, whereas the most common serotype associated with enteritis in Germany is Lior 4. Two of 27 patients with Guillain-Barré syndrome had ganglioside-specific IgA antibodies; 1 of 32 patients, antibodies of IgM; and 4 of 31 patients, antibodies of IgG class. There was no correlation between severity, type (axonal versus demyelinating), and outcome of the disease and the presence or absence of a humoral immune response to C. jejuni or to glycoconjugates. Our findings do not support previous suggestions that a preceding C. jejuni infection heralds a poorer outcome or that antibodies to gangliosides carry prognostic significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Role of plasmid-encoded antigens of Yersinia enterocolitica in humoral immunity against secondary Y. enterocolitica infection in mice.

In the present study the role of Yersinia enterocolitica antigens in humoral immunity against secondary Y. enterocolitica infection has been investigated. For this purpose, BALB/c mice, 4 weeks after immunization by primary infection with a sublethal dose of various Y. enterocolitica strains and mutant strains, were challenged with a lethal dose of highly virulent Y. enterocolitica strains of serotype O:8. As evident from the survival rate and protection against bacterial growth in the spleens of mice, only immunization with wild-type or attenuated strains harbouring an intact virulence plasmid mediated protection against a lethal challenge. Protection by immunization with plasmid-harbouring strains correlated with persistence of the bacteria in spleens for at least 7 days after immunization and high serum titres of Yersinia-specific antibodies directed against both chromosomal and plasmid-encoded determinants. Furthermore, the adoptive transfer of the purified IgG fraction of a rabbit serum specific for the adhesin YadA encoded by virulence plasmid pO8 from Y. enterocolitica O:8 mediated protection against a lethal challenge with the serotype O:8 strain harbouring the virulence plasmid pO8 but did not mediate protection when this strain harboured the virulence plasmid pO9 from serotype O:9. In summary, the results demonstrate that in our experimental mouse infection model: (i) the presence of the intact virulence plasmid in an immunizing Y. enterocolitica strain is essential for induction of protection against a lethal challenge with highly virulent Y. enterocolitica and (ii) that antibodies against plasmid-encoded determinants of Y. enterocolitica, especially YadA, are of major importance for achievement of protective immunity in mice.

Animals↗
PubMed1993

The TonB protein of Yersinia enterocolitica and its interactions with TonB-box proteins.

The tonB gene is required for energy-dependent transport processes across the outer membrane of gram-negative bacteria. Using the antibiotics albomycin and ferrimycin, a tonB mutant of Yersinia enterocolitica was isolated. Comparison of the tonB mutant with the parent strain revealed that in Y. enterocolitica the uptake of ferrioxamine, ferrichrome, pesticin and heme is TonB-dependent. The tonB gene from Y. enterocolitica was sequenced and found to be similar to those of other Enterobacteria. The Y. enterocolitica tonB gene complemented a Y. enterocolitica tonB mutant. In contrast, some TonB functions of an Escherichia coli tonB mutant were not restored by the tonB gene of Y. enterocolitica. The observed differences in the ability to complement E. coli TonB functions correlated with the degree to which the TonB boxes of the receptors and colicins differed from the TonB box consensus sequence. Furthermore, the N-terminal membrane anchor of the TonB proteins and the TolA protein are likely to form an alpha-helix with an identical sequence motif (SHLS) located at one face of the alpha-helix, suggesting this region to be involved in the functional cross-talk between the TonB-ExbBD- and TolABQR-dependent transport systems across the outer membrane.

Amino Acid Sequence↗
PubMed1993

Coexistence of heterogeneous populations of Toxoplasma gondii parasites within parasitophorous vacuoles of murine macrophages as revealed by a bradyzoite-specific monoclonal antibody.

The expression of bradyzoite-specific antigens (Bsa) of Toxoplasma gondii was studied in murine bone-marrow-derived macrophages that had previously been infected with tachyzoites. Growth conditions that allowed only restricted replication of Toxoplasma gondii resulted in heterogeneous populations; (1) Bsa-positive and Bsa-negative parasites could be observed within one parasitophorous vacuole (heterogeneous vacuole community), and (2) homogeneous Bsa-positive and homogeneous Bsa-negative vacuole communities coexisted within one macrophage host cell. These observations suggest that stage conversion does not seem to be a synchronous event for a vacuole community.

Animals↗
PubMed1993

Toxoplasma gondii: uptake of fetuin and identification of a 15-kDa fetuin-binding protein.

Lectin-binding studies demonstrated the presence of a 68-kDa glycoprotein in tachyzoites of Toxoplasma gondii harvested from P388D1 macrophage cell cultures but not in tachyzoites maintained in peritoneal cavities of NMRI mice. This protein was identified as the embryonic protein fetuin that regularly is contained in fetal calf serum, a component of cell-culture media. Uptake of fetuin by T. gondii was demonstrated by intracellular localization of this protein. As shown by latex agglutination and immunofluorescence, no specific binding of fetuin to the parasite's surface was detected. Using affinity chromatography on fetuin-agarose, it was demonstrated that fetuin bound specifically to a 15-kDa antigen of tachyzoites. As revealed by inhibition studies with sialic acid and the lectin Sambucus nigra agglutinin, the 15-kDa protein probably recognized glycan structures of fetuin.

Animals↗
PubMed1993

[Mechanisms of resistance to beta-lactam antibiotics].

Beta-lactam antibiotics share the structural feature of a beta-lactam ring. This feature is responsible for inhibition of bacterial cell wall synthesis. The target molecules are peptidoglycan cross-linking enzymes (e.g. transpeptidases and carboxypeptidases) which can bind beta-lactam antibiotics (penicillin binding proteins, PBP). Bacterial cell death is initiated by beta-lactam antibiotic-triggered release of autolytic enzymes. In contrast to gram-positive bacteria (absence of an outer membrane) the antibiotic has to penetrate through porins of the outer membrane of gram-negative bacteria before touching PBP's. Bacterial resistance to beta-lactam antibiotics includes modification of porins (permeability barrier) and of targets (low affinity of PBP's for the drug), production of inactivating enzymes (beta-lactamases) and inhibition of release of autolytic enzymes. Moreover, bacteria have developed sophisticated genetic mechanisms to adapt to treatments with novel beta-lactam antibiotics. To allow successful antibiotic treatment of bacterial infection in the future, knowledge about antibiotic resistance mechanisms is required.

Amino Acids↗
PubMed1993

Comparison of a commercial enzyme immunoassay and an immunoblot technique for detection of immunoglobulin A antibodies to Toxoplasma gondii.

A commercial enzyme immunoassay (Platelia-Toxo IgA) and an immunoblot technique were compared with regard to their ability to detect IgA antibodies to the major surface protein P30(SAG1) of Toxoplasma gondii in 105 serum samples from patients with suspected or proven acquired toxoplasmosis. Comparison of the IgA-EIA with the immunoblot technique showed a concordance of 81.0%, with a sensitivity of 92.6% and a specificity of 78.4%. Due to its high sensitivity the IgA-EIA might detect IgA antibodies against Toxoplasma gondii at an early stage of infection, although excessive sensitivity could lead to detection of IgA antibodies for an extended period of time following the onset of infection.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Immunohistological characterization of the cellular immune response against Yersinia enterocolitica in mice: evidence for the involvement of T lymphocytes.

Previous work from this laboratory has demonstrated that cloned T lymphocytes from spleens of Yersinia-infected mice can transfer immunity against Y. enterocolitica into naive animals. In this study, we investigated the cellular immune response to parenteral infection of Yersinia-resistant C57 BL/6 mice with the highly virulent Y. enterocolitica strain WA of serotype O:8 employing immunohistological methods. In the course of the infection the spleen and the liver were the organs most extensively affected. Histologically, three different patterns of inflammatory reactions could be observed: (i) small non-pyogenic granuloma-like lesions (in the liver only), (ii) microabscesses lacking a sharp outline, and (iii) larger abscesses disclosing a distinct cellular border (spleen and liver). Immunohistologically, Y. enterocolitica was detectable within abscesses but not in the small granuloma-like lesions present in the liver. CD11b/18 positive cells (= Mac-1-antigen expressed on macrophages, monocytes, granulocytes and NK-cells) could be shown in Yersinia-induced lesions. The number of these cells correlated with the extent of tissue alterations induced by Y. enterocolitica. More strikingly, we were able to demonstrate for the first time that both CD4 (helper) and CD8 (cytotoxic) T lymphocytes are present in Yersinia-induced lesions. In summary, we could demonstrate for the first time that granuloma-like lesions can be induced by Y. enterocolitica. Moreover, we supported our recent study suggesting that T lymphocytes are probably involved in the immune response against Y. enterocolitica in mice.

Animals↗
PubMed1993

The cellular immune response against Yersinia enterocolitica in different inbred strains of mice: evidence for an important role of T lymphocytes.

Resistance of mice against infection with Yersinia enterocolitica has been shown to be related neither to the Ity locus coding for resistance against infection with Salmonella typhimurium and other pathogens nor to the H-2 locus. From other mouse infection models, e.g., murine leishmaniasis, there is evidence that a different T cell-dependent regulation of the host immune response in various inbred strains of mice determines the susceptibility to the infectious agent. However, until recently, little was known about the cellular immune response against Y. enterocolitica. Thus, in a first approach we used the highly virulent Y. enterocolitica strain WA of serotype O:8 and different inbred strains of mice (C57 BL/6, Balb/c and athymic T cell-deficient C57 BL/6 nude mice) to investigate the cell-mediated immunity against parenteral infection. Comparison of the median lethal dose and of the net-bacterial growth in the spleens of infected mice indicated that Balb/c mice could be considered as Yersinia-susceptible whereas C57 BL/6 mice were relatively resistant. However, in contrast to normal C57 BL/6, athymic T cell-deficient C57 BL/6 nude mice have proved to be highly susceptible to Yersinia infection suggesting that T cells are required for the elimination of the pathogen. This conclusion was supported by histomorphological and immunohistological results indicating that T lymphocytes were present in Yersinia-induced tissue lesions. Moreover, the adoptive transfer of Yersinia-specific T cell lines and clones into naive animals mediated significant protection against the pathogen in both Yersinia-resistant C57 BL/6 and in Yersinia-susceptible Balb/c mice. These findings emphasize an important role of T lymphocytes in the host response against Y. enterocolitica infection.

Animals↗
PubMed1993

Survey on newly characterized iron uptake systems of Yersinia enterocolitica.

Iron assimilation systems have been shown to be important for virulence in Yersinia enterocolitica. In principle, iron transport in Y. enterocolitica is similarly organized as in Escherichia coli although some differences exist in the siderophores used. A TonB function was identified which in a tonB mutant was complemented by the E. coli tonB gene. Three outer membrane receptors for siderophores were cloned and sequenced: FoxA for ferrioxamine B and E, FcuA for ferrichrome and HemR for heme uptake. In addition, two receptors were identified by mutants: CccA for catechol cephalosporins and FyuA for yersiniabactin, the siderophore produced by virulent yersiniae. In addition, the FyuA protein is assumed to be the pesticin receptor.

Bacterial Proteins↗
PubMed1993

Virulence of Yersinia enterocolitica is closely associated with siderophore production, expression of an iron-repressible outer membrane polypeptide of 65,000 Da and pesticin sensitivity.

Iron-repressible outer membrane proteins (Irp) and siderophore production of Yersinia enterocolitica, serotype 08, were subjected to analysis. Here four Irps of apparent molecular weights of 62,000, 65,000, 74,000 and 75,000 could be identified which were expressed constitutively by a fur mutant. Production of a novel catechol-containing siderophore (denoted yersiniabactin) was detected by siderophore-indicator agar (chrome azurol S) and feeding experiments. Growth support by yersiniabactin under iron-restricted conditions was TonB- and Irp65-dependent and correlated with pesticin-sensitivity of Yersinia enterocolitica and Escherichia coli O. From these results we conclude that Irp65 of Y. enterocolitica functions as yersiniabactin receptor (FyuA) and as pesticin receptor. By immunoblotting using rabbit antibodies against Irp65 and chrome azurol S-agar, we were able to demonstrate that all tested mouse-lethal Y. enterocolitica and Yersinia pseudotuberculosis strains of different serotypes express siderophores and Irp65. Moreover, the anti-Irp65 rabbit serum did not cross-react with the known iron-repressible high-molecular-weight proteins (HMWPs). Evidently, the mouse lethality trait in enteropathogenic Yersinia spp. is closely associated with a novel iron-uptake system, comprising the production of a siderophore and a siderophore receptor of apparent molecular mass 65,000 Da.

Animals↗