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  1. AU="Jennifer A Gaddy"
  2. AU="Tuccar, Eray"
  3. AU="Koch, Karen E"
  4. AU="Kelly, Allicia P"
  5. AU=Kakinuma Takashi
  6. AU="Nachira, Lorenza"
  7. AU="Wei, Xiang"
  8. AU="Daniell, Esther"
  9. AU="Chou, Chau-Wen"
  10. AU=Kaur Supreet
  11. AU="Yun, Joho"
  12. AU="Tran, Bao G"
  13. AU="Ou Li"
  14. AU="Ting Chen" AU="Ting Chen"
  15. AU="Wilson, Jaymi"
  16. AU="Vane, Christopher H"
  17. AU="Mabbott, Donald"
  18. AU="Martín-Trejo, Jorge Alfonso"
  19. AU=Rieder Hans L

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  1. Artikel ; Online: Is space the final frontier for mitochondrial study?

    Kit Neikirk / Dominique C Stephens / Heather K Beasley / Andrea G Marshall / Jennifer A Gaddy / Steven M Damo / Antentor Hinton

    BioTechniques (2023)

    2023  

    Abstract: Tweetable abstract This perspective considers several avenues for future research on mitochondrial dynamics, stress, and DNA in outer space. ...

    Abstract Tweetable abstract This perspective considers several avenues for future research on mitochondrial dynamics, stress, and DNA in outer space.
    Schlagwörter metabolism ; mitochondria ; mitochondrial structure ; space travel ; Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2023-12-01T00:00:00Z
    Verlag Future Science Ltd
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Helicobacter pylori

    Kathryn P. Haley / Jennifer A. Gaddy

    International Journal of Genomics, Vol

    Genomic Insight into the Host-Pathogen Interaction

    2015  Band 2015

    Schlagwörter Genetics ; QH426-470 ; Biology (General) ; QH301-705.5 ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2015-01-01T00:00:00Z
    Verlag Hindawi Publishing Corporation
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: The PAS Domain-Containing Protein HeuR Regulates Heme Uptake in Campylobacter jejuni

    Jeremiah G. Johnson / Jennifer A. Gaddy / Victor J. DiRita

    mBio, Vol 7, Iss 6, p e01691-

    2016  Band 16

    Abstract: Campylobacter jejuni is a leading cause of bacterially derived gastroenteritis. A previous mutant screen demonstrated that the heme uptake system (Chu) is required for full colonization of the chicken gastrointestinal tract. Subsequent work identified a ... ...

    Abstract Campylobacter jejuni is a leading cause of bacterially derived gastroenteritis. A previous mutant screen demonstrated that the heme uptake system (Chu) is required for full colonization of the chicken gastrointestinal tract. Subsequent work identified a PAS domain-containing regulator, termed HeuR, as being required for chicken colonization. Here we confirm that both the heme uptake system and HeuR are required for full chicken gastrointestinal tract colonization, with the heuR mutant being particularly affected during competition with wild-type C. jejuni. Transcriptomic analysis identified the chu genes—and those encoding other iron uptake systems—as regulatory targets of HeuR. Purified HeuR bound the chuZA promoter region in electrophoretic mobility shift assays. Consistent with a role for HeuR in chu expression, heuR mutants were unable to efficiently use heme as a source of iron under iron-limiting conditions, and mutants exhibited decreased levels of cell-associated iron by mass spectrometry. Finally, we demonstrate that an heuR mutant of C. jejuni is resistant to hydrogen peroxide and that this resistance correlates to elevated levels of catalase activity. These results indicate that HeuR directly and positively regulates iron acquisition from heme and negatively impacts catalase activity by an as yet unidentified mechanism in C. jejuni.
    Schlagwörter Science ; Q ; Microbiology ; QR1-502
    Thema/Rubrik (Code) 571 ; 570
    Sprache Englisch
    Erscheinungsdatum 2016-11-01T00:00:00Z
    Verlag American Society for Microbiology
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Genetically distinct Group B Streptococcus strains induce varying macrophage cytokine responses.

    Rebecca A Flaherty / Elena C Borges / Jessica A Sutton / David M Aronoff / Jennifer A Gaddy / Margaret G Petroff / Shannon D Manning

    PLoS ONE, Vol 14, Iss 9, p e

    2019  Band 0222910

    Abstract: Group B Streptococcus (GBS) is an opportunistic pathogen that causes preterm birth and neonatal disease. Although GBS is known to exhibit vast diversity in virulence across strains, the mechanisms of GBS-associated pathogenesis are incompletely ... ...

    Abstract Group B Streptococcus (GBS) is an opportunistic pathogen that causes preterm birth and neonatal disease. Although GBS is known to exhibit vast diversity in virulence across strains, the mechanisms of GBS-associated pathogenesis are incompletely understood. We hypothesized that GBS strains of different genotypes would vary in their ability to elicit host inflammatory responses, and that strains associated with neonatal disease would induce different cytokine profiles than those associated with colonization. Using a multiplexed, antibody-based protein detection array, we found that production of a discrete number of inflammatory mediators by THP-1 macrophage-like cells was universally induced in response to challenge with each of five genetically distinct GBS isolates, while other responses appeared to be strain-specific. Key array responses were validated by ELISA using the initial five strains as well as ten additional strains with distinct genotypic and phenotypic characteristics. Interestingly, IL-6 was significantly elevated following infection with neonatal infection-associated sequence type (ST)-17 strains and among strains possessing capsule (cps) type III. Significant differences in production of IL1-β, IL-10 and MCP-2 were also identified across STs and cps types. These data support our hypothesis and suggest that unique host innate immune responses reflect strain-specific differences in virulence across GBS isolates. Such data might inform the development of improved diagnostic or prognostic strategies against invasive GBS infections.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2019-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: Peptidomimetic Small Molecules Disrupt Type IV Secretion System Activity in Diverse Bacterial Pathogens

    Carrie L. Shaffer / James A. D. Good / Santosh Kumar / K. Syam Krishnan / Jennifer A. Gaddy / John T. Loh / Joseph Chappell / Fredrik Almqvist / Timothy L. Cover / Maria Hadjifrangiskou

    mBio, Vol 7, Iss 2, p e00221-

    2016  Band 16

    Abstract: Bacteria utilize complex type IV secretion systems (T4SSs) to translocate diverse effector proteins or DNA into target cells. Despite the importance of T4SSs in bacterial pathogenesis, the mechanism by which these translocation machineries deliver cargo ... ...

    Abstract Bacteria utilize complex type IV secretion systems (T4SSs) to translocate diverse effector proteins or DNA into target cells. Despite the importance of T4SSs in bacterial pathogenesis, the mechanism by which these translocation machineries deliver cargo across the bacterial envelope remains poorly understood, and very few studies have investigated the use of synthetic molecules to disrupt T4SS-mediated transport. Here, we describe two synthetic small molecules (C10 and KSK85) that disrupt T4SS-dependent processes in multiple bacterial pathogens. Helicobacter pylori exploits a pilus appendage associated with the cag T4SS to inject an oncogenic effector protein (CagA) and peptidoglycan into gastric epithelial cells. In H. pylori, KSK85 impedes biogenesis of the pilus appendage associated with the cag T4SS, while C10 disrupts cag T4SS activity without perturbing pilus assembly. In addition to the effects in H. pylori, we demonstrate that these compounds disrupt interbacterial DNA transfer by conjugative T4SSs in Escherichia coli and impede vir T4SS-mediated DNA delivery by Agrobacterium tumefaciens in a plant model of infection. Of note, C10 effectively disarmed dissemination of a derepressed IncF plasmid into a recipient bacterial population, thus demonstrating the potential of these compounds in mitigating the spread of antibiotic resistance determinants driven by conjugation. To our knowledge, this study is the first report of synthetic small molecules that impair delivery of both effector protein and DNA cargos by diverse T4SSs.
    Schlagwörter Science ; Q ; Microbiology ; QR1-502
    Thema/Rubrik (Code) 612
    Sprache Englisch
    Erscheinungsdatum 2016-04-01T00:00:00Z
    Verlag American Society for Microbiology
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: Effect of ethanol on differential protein production and expression of potential virulence functions in the opportunistic pathogen Acinetobacter baumannii.

    Chika C Nwugo / Brock A Arivett / Daniel L Zimbler / Jennifer A Gaddy / Ashley M Richards / Luis A Actis

    PLoS ONE, Vol 7, Iss 12, p e

    2012  Band 51936

    Abstract: Acinetobacter baumannii persists in the medical environment and causes severe human nosocomial infections. Previous studies showed that low-level ethanol exposure increases the virulence of A. baumannii ATCC 17978. To better understand the mechanisms ... ...

    Abstract Acinetobacter baumannii persists in the medical environment and causes severe human nosocomial infections. Previous studies showed that low-level ethanol exposure increases the virulence of A. baumannii ATCC 17978. To better understand the mechanisms involved in this response, 2-D gel electrophoresis combined with mass spectrometry was used to investigate differential protein production in bacteria cultured in the presence or absence of ethanol. This approach showed that the presence of ethanol significantly induces and represses the production of 22 and 12 proteins, respectively. Although over 25% of the ethanol-induced proteins were stress-response related, the overall bacterial viability was uncompromised when cultured under these conditions. Production of proteins involved in lipid and carbohydrate anabolism was increased in the presence of ethanol, a response that correlates with increased carbohydrate biofilm content, enhanced biofilm formation on abiotic surfaces and decrease bacterial motility on semi-solid surfaces. The presence of ethanol also induced the acidification of bacterial cultures and the production of indole-3-acetic acid (IAA), a ubiquitous plant hormone that signals bacterial stress-tolerance and promotes plant-bacteria interactions. These responses could be responsible for the significantly enhanced virulence of A. baumannii ATCC 17978 cells cultured in the presence of ethanol when tested with the Galleria mellonella experimental infection model. Taken together, these observations provide new insights into the effect of ethanol in bacterial virulence. This alcohol predisposes the human host to infections by A. baumannii and could favor the survival and adaptation of this pathogen to medical settings and adverse host environments.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 660
    Sprache Englisch
    Erscheinungsdatum 2012-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: The innate immune protein calprotectin promotes Pseudomonas aeruginosa and Staphylococcus aureus interaction

    Catherine A. Wakeman / Jessica L. Moore / Michael J. Noto / Yaofang Zhang / Marc D. Singleton / Boone M. Prentice / Benjamin A. Gilston / Ryan S. Doster / Jennifer A. Gaddy / Walter J. Chazin / Richard M. Caprioli / Eric P. Skaar

    Nature Communications, Vol 7, Iss 1, Pp 1-

    2016  Band 12

    Abstract: Co-infections with Pseudomonas aeruginosa and Staphylococcus aureus are common in cystic fibrosis patients. Here, the authors show that metal depletion induced by a host protein, calprotectin, promotes co-existence of both pathogens by inhibiting ... ...

    Abstract Co-infections with Pseudomonas aeruginosa and Staphylococcus aureus are common in cystic fibrosis patients. Here, the authors show that metal depletion induced by a host protein, calprotectin, promotes co-existence of both pathogens by inhibiting production of anti-staphylococcal molecules by P. aeruginosa.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2016-06-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: Functional plasticity in the type IV secretion system of Helicobacter pylori.

    Roberto M Barrozo / Cara L Cooke / Lori M Hansen / Anna M Lam / Jennifer A Gaddy / Elizabeth M Johnson / Taryn A Cariaga / Giovanni Suarez / Richard M Peek / Timothy L Cover / Jay V Solnick

    PLoS Pathogens, Vol 9, Iss 2, p e

    2013  Band 1003189

    Abstract: Helicobacter pylori causes clinical disease primarily in those individuals infected with a strain that carries the cytotoxin associated gene pathogenicity island (cagPAI). The cagPAI encodes a type IV secretion system (T4SS) that injects the CagA ... ...

    Abstract Helicobacter pylori causes clinical disease primarily in those individuals infected with a strain that carries the cytotoxin associated gene pathogenicity island (cagPAI). The cagPAI encodes a type IV secretion system (T4SS) that injects the CagA oncoprotein into epithelial cells and is required for induction of the pro-inflammatory cytokine, interleukin-8 (IL-8). CagY is an essential component of the H. pylori T4SS that has an unusual sequence structure, in which an extraordinary number of direct DNA repeats is predicted to cause rearrangements that invariably yield in-frame insertions or deletions. Here we demonstrate in murine and non-human primate models that immune-driven host selection of rearrangements in CagY is sufficient to cause gain or loss of function in the H. pylori T4SS. We propose that CagY functions as a sort of molecular switch or perhaps a rheostat that alters the function of the T4SS and "tunes" the host inflammatory response so as to maximize persistent infection.
    Schlagwörter Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2013-02-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  9. Artikel ; Online: The host protein calprotectin modulates the Helicobacter pylori cag type IV secretion system via zinc sequestration.

    Jennifer A Gaddy / Jana N Radin / John T Loh / M Blanca Piazuelo / Thomas E Kehl-Fie / Alberto G Delgado / Florin T Ilca / Richard M Peek / Timothy L Cover / Walter J Chazin / Eric P Skaar / Holly M Scott Algood

    PLoS Pathogens, Vol 10, Iss 10, p e

    2014  Band 1004450

    Abstract: Transition metals are necessary for all forms of life including microorganisms, evidenced by the fact that 30% of all proteins are predicted to interact with a metal cofactor. Through a process termed nutritional immunity, the host actively sequesters ... ...

    Abstract Transition metals are necessary for all forms of life including microorganisms, evidenced by the fact that 30% of all proteins are predicted to interact with a metal cofactor. Through a process termed nutritional immunity, the host actively sequesters essential nutrient metals away from invading pathogenic bacteria. Neutrophils participate in this process by producing several metal chelating proteins, including lactoferrin and calprotectin (CP). As neutrophils are an important component of the inflammatory response directed against the bacterium Helicobacter pylori, a major risk factor for gastric cancer, it was hypothesized that CP plays a role in the host response to H. pylori. Utilizing a murine model of H. pylori infection and gastric epithelial cell co-cultures, the role CP plays in modifying H. pylori -host interactions and the function of the cag Type IV Secretion System (cag T4SS) was investigated. This study indicates elevated gastric levels of CP are associated with the infiltration of neutrophils to the H. pylori-infected tissue. When infected with an H. pylori strain harboring a functional cag T4SS, calprotectin-deficient mice exhibited decreased bacterial burdens and a trend toward increased cag T4SS -dependent inflammation compared to wild-type mice. In vitro data demonstrate that culturing H. pylori with sub-inhibitory doses of CP reduces the activity of the cag T4SS and the biogenesis of cag T4SS-associated pili in a zinc-dependent fashion. Taken together, these data indicate that zinc homeostasis plays a role in regulating the proinflammatory activity of the cag T4SS.
    Schlagwörter Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2014-10-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  10. Artikel ; Online: Helicobacter pylori exploits a unique repertoire of type IV secretion system components for pilus assembly at the bacteria-host cell interface.

    Carrie L Shaffer / Jennifer A Gaddy / John T Loh / Elizabeth M Johnson / Salisha Hill / Ewa E Hennig / Mark S McClain / W Hayes McDonald / Timothy L Cover

    PLoS Pathogens, Vol 7, Iss 9, p e

    2011  Band 1002237

    Abstract: Colonization of the human stomach by Helicobacter pylori is an important risk factor for development of gastric cancer. The H. pylori cag pathogenicity island (cag PAI) encodes components of a type IV secretion system (T4SS) that translocates the ... ...

    Abstract Colonization of the human stomach by Helicobacter pylori is an important risk factor for development of gastric cancer. The H. pylori cag pathogenicity island (cag PAI) encodes components of a type IV secretion system (T4SS) that translocates the bacterial oncoprotein CagA into gastric epithelial cells, and CagL is a specialized component of the cag T4SS that binds the host receptor α5β1 integrin. Here, we utilized a mass spectrometry-based approach to reveal co-purification of CagL, CagI (another integrin-binding protein), and CagH (a protein with weak sequence similarity to CagL). These three proteins are encoded by contiguous genes in the cag PAI, and are detectable on the bacterial surface. All three proteins are required for CagA translocation into host cells and H. pylori-induced IL-8 secretion by gastric epithelial cells; however, these proteins are not homologous to components of T4SSs in other bacterial species. Scanning electron microscopy analysis reveals that these proteins are involved in the formation of pili at the interface between H. pylori and gastric epithelial cells. ΔcagI and ΔcagL mutant strains fail to form pili, whereas a ΔcagH mutant strain exhibits a hyperpiliated phenotype and produces pili that are elongated and thickened compared to those of the wild-type strain. This suggests that pilus dimensions are regulated by CagH. A conserved C-terminal hexapeptide motif is present in CagH, CagI, and CagL. Deletion of these motifs results in abrogation of CagA translocation and IL-8 induction, and the C-terminal motifs of CagI and CagL are required for formation of pili. In summary, these results indicate that CagH, CagI, and CagL are components of a T4SS subassembly involved in pilus biogenesis, and highlight the important role played by unique constituents of the H. pylori cag T4SS.
    Schlagwörter Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2011-09-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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