LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 194

Search options

  1. Article: The Impact of

    Fromm, Katja / Dehio, Christoph

    Frontiers in microbiology

    2021  Volume 12, Page(s) 762582

    Abstract: ... ...

    Abstract Bartonella
    Language English
    Publishing date 2021-12-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2021.762582
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: Structure-function analysis of the cyclic β-1,2-glucan synthase from Agrobacterium tumefaciens.

    Sedzicki, Jaroslaw / Ni, Dongchun / Lehmann, Frank / Stahlberg, Henning / Dehio, Christoph

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 1844

    Abstract: The synthesis of complex sugars is a key aspect of microbial biology. Cyclic β-1,2-glucan (CβG) is a circular polysaccharide critical for host interactions of many bacteria, including major pathogens of humans (Brucella) and plants (Agrobacterium). CβG ... ...

    Abstract The synthesis of complex sugars is a key aspect of microbial biology. Cyclic β-1,2-glucan (CβG) is a circular polysaccharide critical for host interactions of many bacteria, including major pathogens of humans (Brucella) and plants (Agrobacterium). CβG is produced by the cyclic glucan synthase (Cgs), a multi-domain membrane protein. So far, its structure as well as the mechanism underlining the synthesis have not been clarified. Here we use cryo-electron microscopy (cryo-EM) and functional approaches to study Cgs from A. tumefaciens. We determine the structure of this complex protein machinery and clarify key aspects of CβG synthesis, revealing a distinct mechanism that uses a tyrosine-linked oligosaccharide intermediate in cycles of polymerization and processing of the glucan chain. Our research opens possibilities for combating pathogens that rely on polysaccharide virulence factors and may lead to synthetic biology approaches for producing complex cyclic sugars.
    MeSH term(s) Humans ; Agrobacterium tumefaciens/metabolism ; Brucella abortus/metabolism ; Cryoelectron Microscopy ; beta-Glucans/metabolism ; Glucans/metabolism ; Sugars/metabolism ; Glucosyltransferases
    Chemical Substances beta-1,2-glucan (9051-99-4) ; glucan synthase (EC 2.4.1.-) ; beta-Glucans ; Glucans ; Sugars ; Glucosyltransferases (EC 2.4.1.-)
    Language English
    Publishing date 2024-02-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-45415-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: Bartonella effector protein C mediates actin stress fiber formation via recruitment of GEF-H1 to the plasma membrane.

    Marlaire, Simon / Dehio, Christoph

    PLoS pathogens

    2021  Volume 17, Issue 1, Page(s) e1008548

    Abstract: Bartonellae are Gram-negative facultative-intracellular pathogens that use a type-IV-secretion system (T4SS) to translocate a cocktail of Bartonella effector proteins (Beps) into host cells to modulate diverse cellular functions. BepC was initially ... ...

    Abstract Bartonellae are Gram-negative facultative-intracellular pathogens that use a type-IV-secretion system (T4SS) to translocate a cocktail of Bartonella effector proteins (Beps) into host cells to modulate diverse cellular functions. BepC was initially reported to act in concert with BepF in triggering major actin cytoskeletal rearrangements that result in the internalization of a large bacterial aggregate by the so-called 'invasome'. Later, infection studies with bepC deletion mutants and ectopic expression of BepC have implicated this effector in triggering an actin-dependent cell contractility phenotype characterized by fragmentation of migrating cells due to deficient rear detachment at the trailing edge, and BepE was shown to counterbalance this remarkable phenotype. However, the molecular mechanism of how BepC triggers cytoskeletal changes and the host factors involved remained elusive. Using infection assays, we show here that T4SS-mediated transfer of BepC is sufficient to trigger stress fiber formation in non-migrating epithelial cells and additionally cell fragmentation in migrating endothelial cells. Interactomic analysis revealed binding of BepC to a complex of the Rho guanine nucleotide exchange factor GEF-H1 and the serine/threonine-protein kinase MRCKα. Knock-out cell lines revealed that only GEF-H1 is required for mediating BepC-triggered stress fiber formation and inhibitor studies implicated activation of the RhoA/ROCK pathway downstream of GEF-H1. Ectopic co-expression of tagged versions of GEF-H1 and BepC truncations revealed that the C-terminal 'Bep intracellular delivery' (BID) domain facilitated anchorage of BepC to the plasma membrane, whereas the N-terminal 'filamentation induced by cAMP' (FIC) domain facilitated binding of GEF-H1. While FIC domains typically mediate post-translational modifications, most prominently AMPylation, a mutant with quadruple amino acid exchanges in the putative active site indicated that the BepC FIC domain acts in a non-catalytic manner to activate GEF-H1. Our data support a model in which BepC activates the RhoA/ROCK pathway by re-localization of GEF-H1 from microtubules to the plasma membrane.
    MeSH term(s) Actins/metabolism ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Bartonella/metabolism ; Cell Membrane/metabolism ; Cytoskeleton/metabolism ; Endothelial Cells/cytology ; Endothelial Cells/metabolism ; HeLa Cells ; Humans ; Protein C/genetics ; Protein C/metabolism ; Rho Guanine Nucleotide Exchange Factors/genetics ; Rho Guanine Nucleotide Exchange Factors/metabolism ; Stress Fibers/physiology
    Chemical Substances ARHGEF2 protein, human ; Actins ; Bacterial Proteins ; Protein C ; Rho Guanine Nucleotide Exchange Factors
    Language English
    Publishing date 2021-01-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7366
    ISSN (online) 1553-7374
    ISSN 1553-7366
    DOI 10.1371/journal.ppat.1008548
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Adaptive immune defense prevents Bartonella persistence upon trans-placental transmission.

    Siewert, Lena K / Dehio, Christoph / Pinschewer, Daniel D

    PLoS pathogens

    2022  Volume 18, Issue 5, Page(s) e1010489

    Abstract: Vertical transmission of Bartonella infection has been reported for several mammalian species including mice and humans. Accordingly, it is commonly held that acquired immunological tolerance contributes critically to the high prevalence of Bartonellae ... ...

    Abstract Vertical transmission of Bartonella infection has been reported for several mammalian species including mice and humans. Accordingly, it is commonly held that acquired immunological tolerance contributes critically to the high prevalence of Bartonellae in wild-ranging rodent populations. Here we studied an experimental model of Bartonella infection in mice to assess the impact of maternal and newborn immune defense on vertical transmission and bacterial persistence in the offspring, respectively. Congenital infection was frequently observed in B cell-deficient mothers but not in immunocompetent dams, which correlated with a rapid onset of an antibacterial antibody response in infected WT animals. Intriguingly, B cell-deficient offspring with congenital infection exhibited long-term bacteremia whereas B cell-sufficient offspring cleared bacteremia within a few weeks after birth. Clearance of congenital Bartonella infection resulted in immunity against bacterial rechallenge, with the animals mounting Bartonella-neutralizing antibody responses of normal magnitude. These observations reveal a key role for humoral immune defense by the mother and offspring in preventing and eliminating vertical transmission. Moreover, congenital Bartonella infection does not induce humoral immune tolerance but results in anti-bacterial immunity, questioning the contribution of neonatal tolerance to Bartonella prevalence in wild-ranging rodents.
    MeSH term(s) Animals ; Bacteremia/microbiology ; Bartonella ; Bartonella Infections ; Female ; Infectious Disease Transmission, Vertical ; Mammals ; Mice ; Placenta ; Pregnancy
    Language English
    Publishing date 2022-05-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1010489
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: Antibiotic persistence of intracellular Brucella abortus.

    Mode, Selma / Ketterer, Maren / Québatte, Maxime / Dehio, Christoph

    PLoS neglected tropical diseases

    2022  Volume 16, Issue 7, Page(s) e0010635

    Abstract: Background: Human brucellosis caused by the facultative intracellular pathogen Brucella spp. is an endemic bacterial zoonosis manifesting as acute or chronic infections with high morbidity. Treatment typically involves a combination therapy of two ... ...

    Abstract Background: Human brucellosis caused by the facultative intracellular pathogen Brucella spp. is an endemic bacterial zoonosis manifesting as acute or chronic infections with high morbidity. Treatment typically involves a combination therapy of two antibiotics for several weeks to months, but despite this harsh treatment relapses occur at a rate of 5-15%. Although poor compliance and reinfection may account for a fraction of the observed relapse cases, it is apparent that the properties of the infectious agent itself may play a decisive role in this phenomenon.
    Methodology/principal findings: We used B. abortus carrying a dual reporter in a macrophage infection model to gain a better understanding of the efficacy of recommended therapies in cellulo. For this we used automated fluorescent microscopy as a prime read-out and developed specific CellProfiler pipelines to score infected macrophages at the population and the single cell level. Combining microscopy of constitutive and induced reporters with classical CFU determination, we quantified the protective nature of the Brucella intracellular lifestyle to various antibiotics and the ability of B. abortus to persist in cellulo despite harsh antibiotic treatments.
    Conclusion/significance: We demonstrate that treatment of infected macrophages with antibiotics at recommended concentrations fails to fully prevent growth and persistence of B. abortus in cellulo, which may be explained by a protective nature of the intracellular niche(s). Moreover, we show the presence of bona fide intracellular persisters upon antibiotic treatment, which are metabolically active and retain the full infectious potential, therefore constituting a plausible reservoir for reinfection and relapse. In conclusion, our results highlight the need to extend the spectrum of models to test new antimicrobial therapies for brucellosis to better reflect the in vivo infection environment, and to develop therapeutic approaches targeting the persister subpopulation.
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Brucella abortus ; Brucellosis/drug therapy ; Brucellosis/microbiology ; Humans ; Macrophages/microbiology ; Reinfection
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2022-07-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2735
    ISSN (online) 1935-2735
    ISSN 1935-2735
    DOI 10.1371/journal.pntd.0010635
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: Bartonella effector protein C mediates actin stress fiber formation via recruitment of GEF-H1 to the plasma membrane.

    Simon Marlaire / Christoph Dehio

    PLoS Pathogens, Vol 17, Iss 1, p e

    2021  Volume 1008548

    Abstract: Bartonellae are Gram-negative facultative-intracellular pathogens that use a type-IV-secretion system (T4SS) to translocate a cocktail of Bartonella effector proteins (Beps) into host cells to modulate diverse cellular functions. BepC was initially ... ...

    Abstract Bartonellae are Gram-negative facultative-intracellular pathogens that use a type-IV-secretion system (T4SS) to translocate a cocktail of Bartonella effector proteins (Beps) into host cells to modulate diverse cellular functions. BepC was initially reported to act in concert with BepF in triggering major actin cytoskeletal rearrangements that result in the internalization of a large bacterial aggregate by the so-called 'invasome'. Later, infection studies with bepC deletion mutants and ectopic expression of BepC have implicated this effector in triggering an actin-dependent cell contractility phenotype characterized by fragmentation of migrating cells due to deficient rear detachment at the trailing edge, and BepE was shown to counterbalance this remarkable phenotype. However, the molecular mechanism of how BepC triggers cytoskeletal changes and the host factors involved remained elusive. Using infection assays, we show here that T4SS-mediated transfer of BepC is sufficient to trigger stress fiber formation in non-migrating epithelial cells and additionally cell fragmentation in migrating endothelial cells. Interactomic analysis revealed binding of BepC to a complex of the Rho guanine nucleotide exchange factor GEF-H1 and the serine/threonine-protein kinase MRCKα. Knock-out cell lines revealed that only GEF-H1 is required for mediating BepC-triggered stress fiber formation and inhibitor studies implicated activation of the RhoA/ROCK pathway downstream of GEF-H1. Ectopic co-expression of tagged versions of GEF-H1 and BepC truncations revealed that the C-terminal 'Bep intracellular delivery' (BID) domain facilitated anchorage of BepC to the plasma membrane, whereas the N-terminal 'filamentation induced by cAMP' (FIC) domain facilitated binding of GEF-H1. While FIC domains typically mediate post-translational modifications, most prominently AMPylation, a mutant with quadruple amino acid exchanges in the putative active site indicated that the BepC FIC domain acts in a non-catalytic manner to activate GEF-H1. Our ...
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  7. Article ; Online: Adaptive immune defense prevents Bartonella persistence upon trans-placental transmission.

    Lena K Siewert / Christoph Dehio / Daniel D Pinschewer

    PLoS Pathogens, Vol 18, Iss 5, p e

    2022  Volume 1010489

    Abstract: Vertical transmission of Bartonella infection has been reported for several mammalian species including mice and humans. Accordingly, it is commonly held that acquired immunological tolerance contributes critically to the high prevalence of Bartonellae ... ...

    Abstract Vertical transmission of Bartonella infection has been reported for several mammalian species including mice and humans. Accordingly, it is commonly held that acquired immunological tolerance contributes critically to the high prevalence of Bartonellae in wild-ranging rodent populations. Here we studied an experimental model of Bartonella infection in mice to assess the impact of maternal and newborn immune defense on vertical transmission and bacterial persistence in the offspring, respectively. Congenital infection was frequently observed in B cell-deficient mothers but not in immunocompetent dams, which correlated with a rapid onset of an antibacterial antibody response in infected WT animals. Intriguingly, B cell-deficient offspring with congenital infection exhibited long-term bacteremia whereas B cell-sufficient offspring cleared bacteremia within a few weeks after birth. Clearance of congenital Bartonella infection resulted in immunity against bacterial rechallenge, with the animals mounting Bartonella-neutralizing antibody responses of normal magnitude. These observations reveal a key role for humoral immune defense by the mother and offspring in preventing and eliminating vertical transmission. Moreover, congenital Bartonella infection does not induce humoral immune tolerance but results in anti-bacterial immunity, questioning the contribution of neonatal tolerance to Bartonella prevalence in wild-ranging rodents.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 572
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  8. Article ; Online: Antibiotic persistence of intracellular Brucella abortus.

    Selma Mode / Maren Ketterer / Maxime Québatte / Christoph Dehio

    PLoS Neglected Tropical Diseases, Vol 16, Iss 7, p e

    2022  Volume 0010635

    Abstract: Background Human brucellosis caused by the facultative intracellular pathogen Brucella spp. is an endemic bacterial zoonosis manifesting as acute or chronic infections with high morbidity. Treatment typically involves a combination therapy of two ... ...

    Abstract Background Human brucellosis caused by the facultative intracellular pathogen Brucella spp. is an endemic bacterial zoonosis manifesting as acute or chronic infections with high morbidity. Treatment typically involves a combination therapy of two antibiotics for several weeks to months, but despite this harsh treatment relapses occur at a rate of 5-15%. Although poor compliance and reinfection may account for a fraction of the observed relapse cases, it is apparent that the properties of the infectious agent itself may play a decisive role in this phenomenon. Methodology/principal findings We used B. abortus carrying a dual reporter in a macrophage infection model to gain a better understanding of the efficacy of recommended therapies in cellulo. For this we used automated fluorescent microscopy as a prime read-out and developed specific CellProfiler pipelines to score infected macrophages at the population and the single cell level. Combining microscopy of constitutive and induced reporters with classical CFU determination, we quantified the protective nature of the Brucella intracellular lifestyle to various antibiotics and the ability of B. abortus to persist in cellulo despite harsh antibiotic treatments. Conclusion/significance We demonstrate that treatment of infected macrophages with antibiotics at recommended concentrations fails to fully prevent growth and persistence of B. abortus in cellulo, which may be explained by a protective nature of the intracellular niche(s). Moreover, we show the presence of bona fide intracellular persisters upon antibiotic treatment, which are metabolically active and retain the full infectious potential, therefore constituting a plausible reservoir for reinfection and relapse. In conclusion, our results highlight the need to extend the spectrum of models to test new antimicrobial therapies for brucellosis to better reflect the in vivo infection environment, and to develop therapeutic approaches targeting the persister subpopulation.
    Keywords Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
    Subject code 616
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  9. Article ; Online: Bartonella gene transfer agent: Evolution, function, and proposed role in host adaptation.

    Québatte, Maxime / Dehio, Christoph

    Cellular microbiology

    2019  Volume 21, Issue 11, Page(s) e13068

    Abstract: The processes underlying host adaptation by bacterial pathogens remain a fundamental question with relevant clinical, ecological, and evolutionary implications. Zoonotic pathogens of the genus Bartonella constitute an exceptional model to study these ... ...

    Abstract The processes underlying host adaptation by bacterial pathogens remain a fundamental question with relevant clinical, ecological, and evolutionary implications. Zoonotic pathogens of the genus Bartonella constitute an exceptional model to study these aspects. Bartonellae have undergone a spectacular diversification into multiple species resulting from adaptive radiation. Specific adaptations of a complex facultative intracellular lifestyle have enabled the colonisation of distinct mammalian reservoir hosts. This remarkable host adaptability has a multifactorial basis and is thought to be driven by horizontal gene transfer (HGT) and recombination among a limited genus-specific pan genome. Recent functional and evolutionary studies revealed that the conserved Bartonella gene transfer agent (BaGTA) mediates highly efficient HGT and could thus drive this evolution. Here, we review the recent progress made towards understanding BaGTA evolution, function, and its role in the evolution and pathogenesis of Bartonella spp. We notably discuss how BaGTA could have contributed to genome diversification through recombination of beneficial traits that underlie host adaptability. We further address how BaGTA may counter the accumulation of deleterious mutations in clonal populations (Muller's ratchet), which are expected to occur through the recurrent transmission bottlenecks during the complex infection cycle of these pathogens in their mammalian reservoir hosts and arthropod vectors.
    MeSH term(s) Adaptation, Physiological/genetics ; Animals ; Bacterial Proteins/genetics ; Bartonella/genetics ; Bartonella/growth & development ; Bartonella/metabolism ; Bartonella/pathogenicity ; Evolution, Molecular ; Gene Transfer, Horizontal/genetics ; Gene Transfer, Horizontal/physiology ; Host Microbial Interactions ; Mutation ; Recombination, Genetic/genetics ; Replication Origin/genetics ; Type IV Secretion Systems/genetics ; Type IV Secretion Systems/metabolism
    Chemical Substances Bacterial Proteins ; Type IV Secretion Systems
    Language English
    Publishing date 2019-07-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1468320-9
    ISSN 1462-5822 ; 1462-5814
    ISSN (online) 1462-5822
    ISSN 1462-5814
    DOI 10.1111/cmi.13068
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article ; Online: Role of distinct type-IV-secretion systems and secreted effector sets in host adaptation by pathogenic Bartonella species.

    Wagner, Alexander / Dehio, Christoph

    Cellular microbiology

    2019  Volume 21, Issue 3, Page(s) e13004

    Abstract: The α-proteobacterial genus Bartonella comprises a large number of facultative intracellular pathogens that share a common lifestyle hallmarked by hemotrophic infection and arthropod transmission. Speciation in the four deep-branching lineages (L1-L4) ... ...

    Abstract The α-proteobacterial genus Bartonella comprises a large number of facultative intracellular pathogens that share a common lifestyle hallmarked by hemotrophic infection and arthropod transmission. Speciation in the four deep-branching lineages (L1-L4) occurred by host adaptation facilitating the establishment of long lasting bacteraemia in specific mammalian reservoir host(s). Two distinct type-IV-secretion systems (T4SSs) acquired horizontally by different Bartonella lineages mediate essential host interactions during infection and represent key innovations for host adaptation. The Trw-T4SS confined to the species-rich L4 mediates host-specific erythrocyte infection and likely has functionally replaced flagella as ancestral virulence factors implicated in erythrocyte colonisation by bartonellae of the other lineages. The VirB/VirD4-T4SS translocates Bartonella effector proteins (Bep) into various host cell types to modulate diverse cellular and innate immune functions involved in systemic spreading of bacteria following intradermal inoculation. Independent acquisition of the virB/virD4/bep locus by L1, L3, and L4 was likely driven by arthropod vectors associated with intradermal inoculation of bacteria rather than facilitating direct access to blood. Subsequently, adaptation to colonise specific niches in the new host has shaped the evolution of complex species-specific Bep repertoires. This diversification of the virulence factor repertoire of Bartonella spp. represents a remarkable example for parallel evolution of host adaptation.
    MeSH term(s) Adaptation, Biological ; Animals ; Arthropods/microbiology ; Bartonella/growth & development ; Bartonella Infections/microbiology ; Disease Transmission, Infectious ; Evolution, Molecular ; Host-Pathogen Interactions ; Mammals ; Type IV Secretion Systems/genetics ; Type IV Secretion Systems/metabolism ; Virulence Factors/genetics ; Virulence Factors/metabolism
    Chemical Substances Type IV Secretion Systems ; Virulence Factors
    Language English
    Publishing date 2019-02-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1468320-9
    ISSN 1462-5822 ; 1462-5814
    ISSN (online) 1462-5822
    ISSN 1462-5814
    DOI 10.1111/cmi.13004
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top