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  1. Article ; Online: Characterizing the Pathogenic Potential of Crohn's Disease-Associated Adherent-Invasive

    Zangara, Megan T / Darwish, Lena / Coombes, Brian K

    EcoSal Plus

    2023  Volume 11, Issue 1, Page(s) eesp00182022

    Abstract: The microbiome of Crohn's disease (CD) patients is composed of a microbial community that is considered dysbiotic and proinflammatory in nature. The overrepresentation ... ...

    Abstract The microbiome of Crohn's disease (CD) patients is composed of a microbial community that is considered dysbiotic and proinflammatory in nature. The overrepresentation of
    MeSH term(s) Humans ; Crohn Disease/metabolism ; Crohn Disease/pathology ; Escherichia coli/genetics ; Escherichia coli Infections ; Inflammatory Bowel Diseases/metabolism ; Inflammatory Bowel Diseases/pathology ; Ileum/metabolism ; Ileum/pathology
    Language English
    Publishing date 2023-05-17
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2324-6200
    ISSN (online) 2324-6200
    DOI 10.1128/ecosalplus.esp-0018-2022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Emergence of invasive Salmonella in Africa.

    Tsai, Caressa N / Coombes, Brian K

    Nature microbiology

    2021  Volume 6, Issue 3, Page(s) 273–274

    MeSH term(s) Africa/epidemiology ; Bacteremia ; Humans ; Salmonella Infections/epidemiology ; Salmonella typhimurium
    Language English
    Publishing date 2021-01-28
    Publishing country England
    Document type Journal Article ; Comment
    ISSN 2058-5276
    ISSN (online) 2058-5276
    DOI 10.1038/s41564-021-00864-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: High-Throughput Chemical Screening for Inhibitors of

    Tsai, Caressa N / Coombes, Brian K

    STAR protocols

    2020  Volume 1, Issue 2, Page(s) 100057

    Abstract: Anti-virulence therapies are under active investigation as antibiotic alternatives; however, their identification from large-scale chemical libraries poses a unique challenge. The dispensability of virulence factors for ... ...

    Abstract Anti-virulence therapies are under active investigation as antibiotic alternatives; however, their identification from large-scale chemical libraries poses a unique challenge. The dispensability of virulence factors for growth
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/antagonists & inhibitors ; Bacterial Proteins/genetics ; Bacteriological Techniques/methods ; High-Throughput Screening Assays/methods ; Membrane Proteins/antagonists & inhibitors ; Membrane Proteins/genetics ; Salmonella typhimurium/drug effects ; Salmonella typhimurium/genetics ; Salmonella typhimurium/pathogenicity
    Chemical Substances Anti-Bacterial Agents ; Bacterial Proteins ; Membrane Proteins ; SPI-2 protein, Salmonella
    Language English
    Publishing date 2020-06-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2020.100057
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Bacterial evolution: Making a host-adapted bacterium.

    Coombes, Brian K

    Nature microbiology

    2016  Volume 1, Page(s) 16010

    MeSH term(s) Bacteria/genetics ; Biological Evolution ; Evolution, Molecular ; Genome, Bacterial ; Host-Pathogen Interactions
    Language English
    Publishing date 2016-02-24
    Publishing country England
    Document type Journal Article ; Comment
    ISSN 2058-5276
    ISSN (online) 2058-5276
    DOI 10.1038/nmicrobiol.2016.10
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  5. Article ; Online: A Nanocomposite Dynamic Covalent Cross-Linked Hydrogel Loaded with Fusidic Acid for Treating Antibiotic-Resistant Infected Wounds.

    Toufanian, Samaneh / Mohammed, Jody / Winterhelt, Erica / Lofts, Andrew / Dave, Ridhdhi / Coombes, Brian K / Hoare, Todd

    ACS applied bio materials

    2024  Volume 7, Issue 3, Page(s) 1947–1957

    Abstract: Methicillin- ... ...

    Abstract Methicillin-resistant
    MeSH term(s) Animals ; Mice ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Fusidic Acid/pharmacology ; Fusidic Acid/therapeutic use ; Methicillin-Resistant Staphylococcus aureus ; Hydrogels/chemistry ; Polyethylene Glycols
    Chemical Substances Anti-Bacterial Agents ; Fusidic Acid (59XE10C19C) ; POEGMA ; Hydrogels ; Polyethylene Glycols (3WJQ0SDW1A)
    Language English
    Publishing date 2024-02-23
    Publishing country United States
    Document type Journal Article
    ISSN 2576-6422
    ISSN (online) 2576-6422
    DOI 10.1021/acsabm.3c01293
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The Role of the Host in Driving Phenotypic Heterogeneity in Salmonella.

    Tsai, Caressa N / Coombes, Brian K

    Trends in microbiology

    2019  Volume 27, Issue 6, Page(s) 508–523

    Abstract: The complex infection environment within hosts exerts unique stresses across tissues and cell types, selecting for phenotypic heterogeneity in bacterial populations. Pathogens maintain variability during infection as a strategy to cope with fluctuating ... ...

    Abstract The complex infection environment within hosts exerts unique stresses across tissues and cell types, selecting for phenotypic heterogeneity in bacterial populations. Pathogens maintain variability during infection as a strategy to cope with fluctuating host immune conditions, leading to diversification of virulence phenotypes. Recent improvements in single-cell analyses have revealed that distinct bacterial subpopulations contribute unique colonization and growth strategies across infection sites. We discuss several examples of host-driven phenotypic heterogeneity in Salmonella populations throughout the course of infection, highlighting how variation in gene expression, growth rate, immune evasion, and metabolic activity contribute to overall bacterial success at the population level. We additionally focus our discussion on the implications of diversity within bacterial communities for antimicrobial efficacy.
    MeSH term(s) Animals ; Anti-Bacterial Agents/pharmacology ; Energy Metabolism ; Genetic Heterogeneity ; Host-Pathogen Interactions/immunology ; Humans ; Immunity, Innate ; Intestinal Mucosa/immunology ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/microbiology ; Microbial Viability ; Phenotype ; Salmonella/drug effects ; Salmonella/physiology ; Salmonella Infections/immunology ; Salmonella Infections/microbiology ; Type III Secretion Systems/genetics ; Virulence/genetics
    Chemical Substances Anti-Bacterial Agents ; Type III Secretion Systems
    Language English
    Publishing date 2019-02-10
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1158963-2
    ISSN 1878-4380 ; 0966-842X
    ISSN (online) 1878-4380
    ISSN 0966-842X
    DOI 10.1016/j.tim.2019.01.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3738: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Screening under infection-relevant conditions reveals chemical sensitivity in multidrug resistant invasive non-typhoidal

    Tsai, Caressa N / Massicotte, Marie-Ange / MacNair, Craig R / Perry, Jordyn N / Brown, Eric D / Coombes, Brian K

    RSC chemical biology

    2023  Volume 4, Issue 8, Page(s) 600–612

    Abstract: Bloodstream infections caused by invasive, non- ... ...

    Abstract Bloodstream infections caused by invasive, non-typhoidal
    Language English
    Publishing date 2023-07-08
    Publishing country England
    Document type Journal Article
    ISSN 2633-0679
    ISSN (online) 2633-0679
    DOI 10.1039/d3cb00014a
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Synthetic Biology Facilitates Semisynthetic Development of Type V Glycopeptide Antibiotics Targeting Vancomycin-Resistant

    Koteva, Kalinka / Xu, Min / Wang, Wenliang / Fiebig-Comyn, Aline A / Cook, Michael A / Coombes, Brian K / Wright, Gerard D

    Journal of medicinal chemistry

    2023  Volume 66, Issue 13, Page(s) 9006–9022

    Abstract: The continued efficacy of glycopeptide antibiotics (GPAs) against Gram-positive bacteria is challenged by the emergence and spread of GPA-resistant pathogens, particularly vancomycin-resistant enterococci (VRE). The growing frequency of GPA resistance ... ...

    Abstract The continued efficacy of glycopeptide antibiotics (GPAs) against Gram-positive bacteria is challenged by the emergence and spread of GPA-resistant pathogens, particularly vancomycin-resistant enterococci (VRE). The growing frequency of GPA resistance propels the need for innovative development of more effective antibiotics. Unlike canonical GPAs like vancomycin, Type V GPAs adopt a distinct mode of action by binding peptidoglycan and blocking the activity of autolysins essential for cell division, rendering them a promising class of antibiotics for further development. In this study, the Type V GPA, rimomycin A, was modified to generate 32 new analogues. Compound
    MeSH term(s) Animals ; Mice ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Anti-Bacterial Agents/chemistry ; Glycopeptides/pharmacology ; Glycopeptides/therapeutic use ; Glycopeptides/chemistry ; Gram-Positive Bacterial Infections/drug therapy ; Gram-Positive Bacterial Infections/microbiology ; Microbial Sensitivity Tests ; Synthetic Biology ; Vancomycin/pharmacology ; Vancomycin/chemistry ; Vancomycin-Resistant Enterococci
    Chemical Substances Anti-Bacterial Agents ; compound 17 (31122-84-6) ; Glycopeptides ; Vancomycin (6Q205EH1VU) ; rimomycin A
    Language English
    Publishing date 2023-06-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.3c00633
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 151: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MB 1: Show issues

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  9. Article ; Online: Molecular basis for CesT recognition of type III secretion effectors in enteropathogenic Escherichia coli.

    Little, Dustin J / Coombes, Brian K

    PLoS pathogens

    2018  Volume 14, Issue 8, Page(s) e1007224

    Abstract: Enteropathogenic Escherichia coli (EPEC) use a needle-like injection apparatus known as the type III secretion system (T3SS) to deliver protein effectors into host cells. Effector translocation is highly stratified in EPEC with the translocated intimin ... ...

    Abstract Enteropathogenic Escherichia coli (EPEC) use a needle-like injection apparatus known as the type III secretion system (T3SS) to deliver protein effectors into host cells. Effector translocation is highly stratified in EPEC with the translocated intimin receptor (Tir) being the first effector delivered into the host. CesT is a multi-cargo chaperone that is required for the secretion of Tir and at least 9 other effectors. However, the structural and mechanistic basis for differential effector recognition by CesT remains unclear. Here, we delineated the minimal CesT-binding region on Tir to residues 35-77 and determined the 2.74 Å structure of CesT bound to an N-terminal fragment of Tir. Our structure revealed that the CesT-binding region in the N-terminus of Tir contains an additional conserved sequence, distinct from the known chaperone-binding β-motif, that we termed the CesT-extension motif because it extends the β-sheet core of CesT. This motif is also present in the C-terminus of Tir that we confirmed to be a unique second CesT-binding region. Point mutations that disrupt CesT-binding to the N- or C-terminus of Tir revealed that the newly identified carboxy-terminal CesT-binding region was required for efficient Tir translocation into HeLa cells and pedestal formation. Furthermore, the CesT-extension motif was identified in the N-terminal region of NleH1, NleH2, and EspZ, and mutations that disrupt this motif reduced translocation of these effectors, and in some cases, overall effector stability, thus validating the universality of this CesT-extension motif. The presence of two CesT-binding regions in Tir, along with the presence of the CesT-extension motif in other highly translocated effectors, may contribute to differential cargo recognition by CesT.
    MeSH term(s) Enteropathogenic Escherichia coli/genetics ; Enteropathogenic Escherichia coli/metabolism ; Escherichia coli Proteins/chemistry ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Gene Expression Regulation, Bacterial ; HeLa Cells ; Humans ; Models, Molecular ; Molecular Chaperones/chemistry ; Molecular Chaperones/genetics ; Molecular Chaperones/metabolism ; Organisms, Genetically Modified ; Protein Binding ; Protein Interaction Domains and Motifs/genetics ; Protein Structure, Quaternary ; Protein Transport
    Chemical Substances CesT protein, E coli ; Escherichia coli Proteins ; Molecular Chaperones
    Language English
    Publishing date 2018-08-17
    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.1007224
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  10. Article ; Online: Emerging and divergent roles of pyrophosphorylated nucleotides in bacterial physiology and pathogenesis.

    Chau, N Y Elizabeth / Ahmad, Shehryar / Whitney, John C / Coombes, Brian K

    PLoS pathogens

    2021  Volume 17, Issue 5, Page(s) e1009532

    Abstract: Bacteria inhabit diverse environmental niches and consequently must modulate their metabolism to adapt to stress. The nucleotide second messengers guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp) (collectively referred to as (p) ... ...

    Abstract Bacteria inhabit diverse environmental niches and consequently must modulate their metabolism to adapt to stress. The nucleotide second messengers guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp) (collectively referred to as (p)ppGpp) are essential for survival during nutrient starvation. (p)ppGpp is synthesized by the RelA-SpoT homologue (RSH) protein family and coordinates the control of cellular metabolism through its combined effect on over 50 proteins. While the role of (p)ppGpp has largely been associated with nutrient limitation, recent studies have shown that (p)ppGpp and related nucleotides have a previously underappreciated effect on different aspects of bacterial physiology, such as maintaining cellular homeostasis and regulating bacterial interactions with a host, other bacteria, or phages. (p)ppGpp produced by pathogenic bacteria facilitates the evasion of host defenses such as reactive nitrogen intermediates, acidic pH, and the complement system. Additionally, (p)ppGpp and pyrophosphorylated derivatives of canonical adenosine nucleotides called (p)ppApp are emerging as effectors of bacterial toxin proteins. Here, we review the RSH protein family with a focus on its unconventional roles during host infection and bacterial competition.
    MeSH term(s) Animals ; Bacteria/metabolism ; Bacterial Infections/metabolism ; Bacterial Infections/microbiology ; Bacterial Infections/pathology ; Bacterial Physiological Phenomena ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Diphosphates/metabolism ; Gene Expression Regulation, Bacterial ; Humans ; Nucleotides/metabolism ; Phosphorylation ; Stress, Physiological
    Chemical Substances Bacterial Proteins ; Diphosphates ; Nucleotides
    Language English
    Publishing date 2021-05-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7366
    ISSN (online) 1553-7374
    ISSN 1553-7366
    DOI 10.1371/journal.ppat.1009532
    Database MEDical Literature Analysis and Retrieval System OnLINE

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