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  1. Article ; Online: Unraveling neutrophil-

    Mecsas, Joan

    F1000Research

    2019  Volume 8

    Abstract: The human and animal ... ...

    Abstract The human and animal pathogens
    MeSH term(s) Adhesins, Bacterial ; Animals ; Bacterial Outer Membrane Proteins ; Gene Expression Regulation, Bacterial ; Humans ; Neutrophils/physiology ; Yersinia/genetics ; Yersinia/pathogenicity ; Yersinia Infections/immunology
    Chemical Substances Adhesins, Bacterial ; Bacterial Outer Membrane Proteins
    Language English
    Publishing date 2019-07-11
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2699932-8
    ISSN 2046-1402 ; 2046-1402
    ISSN (online) 2046-1402
    ISSN 2046-1402
    DOI 10.12688/f1000research.18940.1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Eat Your Vitamin A: A Role for Retinoic Acid in the Development of Microfold Cells.

    Fasciano, Alyssa C / Mecsas, Joan

    Gastroenterology

    2020  Volume 159, Issue 1, Page(s) 34–36

    MeSH term(s) Cell Differentiation ; Humans ; Lymphotoxin-alpha ; Tretinoin ; Vitamin A ; Vitamin A Deficiency
    Chemical Substances Lymphotoxin-alpha ; Vitamin A (11103-57-4) ; Tretinoin (5688UTC01R)
    Language English
    Publishing date 2020-05-13
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 80112-4
    ISSN 1528-0012 ; 0016-5085
    ISSN (online) 1528-0012
    ISSN 0016-5085
    DOI 10.1053/j.gastro.2020.05.029
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  3. Article ; Online: Critical role of growth medium for detecting drug interactions in Gram-negative bacteria that model

    Davis, Kathleen P / Morales, Yoelkys / Ende, Rachel J / Peters, Ryan / McCabe, Anne L / Mecsas, Joan / Aldridge, Bree B

    mBio

    2024  Volume 15, Issue 3, Page(s) e0015924

    Abstract: The rise in infections caused by multidrug-resistant (MDR) bacteria has necessitated a variety of clinical approaches, including the use of antibiotic combinations. Here, we tested the hypothesis that drug-drug interactions vary in different media, and ... ...

    Abstract The rise in infections caused by multidrug-resistant (MDR) bacteria has necessitated a variety of clinical approaches, including the use of antibiotic combinations. Here, we tested the hypothesis that drug-drug interactions vary in different media, and determined which
    Importance: Drug-resistant bacterial infections are a growing concern and have only continued to increase during the SARS-CoV-2 pandemic. Though not routinely used for Gram-negative bacteria, drug combinations are sometimes used for serious infections and may become more widely used as the prevalence of extremely drug-resistant organisms increases. To date, reliable methods are not available for identifying beneficial drug combinations for a particular infection. Our study shows variability across strains in how drug interactions are impacted by growth conditions. It also demonstrates that testing drug combinations in tissue-relevant growth conditions for some strains better models what happens during infection and may better inform combination therapy selection.
    MeSH term(s) Mice ; Animals ; Anti-Bacterial Agents/pharmacology ; Gram-Negative Bacteria ; Drug Resistance, Multiple, Bacterial ; Drug Interactions ; Klebsiella pneumoniae ; Drug Combinations ; Microbial Sensitivity Tests ; Pseudomonas aeruginosa
    Chemical Substances Anti-Bacterial Agents ; Drug Combinations
    Language English
    Publishing date 2024-02-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.00159-24
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Role of the Yersinia pseudotuberculosis Virulence Plasmid in Pathogen-Phagocyte Interactions in Mesenteric Lymph Nodes.

    Bliska, James B / Brodsky, Igor E / Mecsas, Joan

    EcoSal Plus

    2021  Volume 9, Issue 2, Page(s) eESP00142021

    Abstract: Yersinia pseudotuberculosis is ... ...

    Abstract Yersinia pseudotuberculosis is an
    MeSH term(s) Animals ; Lymph Nodes ; Mice ; Monocytes ; Plasmids ; Virulence ; Yersinia pseudotuberculosis/genetics
    Language English
    Publishing date 2021-10-27
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2324-6200
    ISSN (online) 2324-6200
    DOI 10.1128/ecosalplus.ESP-0014-2021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Editorial overview: Host-pathogen interactions shaped through evolutionary and regulatory processes.

    Buchrieser, Carmen / Mecsas, Joan

    Current opinion in microbiology

    2018  Volume 41, Page(s) v–viii

    MeSH term(s) Bacteria ; Biological Evolution ; Host-Pathogen Interactions ; Humans ; Microbiota
    Language English
    Publishing date 2018-03-19
    Publishing country England
    Document type Editorial ; Comment
    ZDB-ID 1418474-6
    ISSN 1879-0364 ; 1369-5274
    ISSN (online) 1879-0364
    ISSN 1369-5274
    DOI 10.1016/j.mib.2018.02.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5514: Show issues Location:
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  6. Article ; Online: Promises and Challenges of the Type Three Secretion System Injectisome as an Antivirulence Target.

    Fasciano, Alyssa C / Shaban, Lamyaa / Mecsas, Joan

    EcoSal Plus

    2019  Volume 8, Issue 2

    Abstract: Antibiotic resistance is a major public health threat that has stimulated the scientific community to search for nontraditional therapeutic targets. Because virulence, but not the growth, of many Gram-negative bacterial pathogens depends on the ... ...

    Abstract Antibiotic resistance is a major public health threat that has stimulated the scientific community to search for nontraditional therapeutic targets. Because virulence, but not the growth, of many Gram-negative bacterial pathogens depends on the multicomponent type three secretion system injectisome (T3SSi), the T3SSi has been an attractive target for identifying small molecules, peptides, and monoclonal antibodies that inhibit its function to render the pathogen avirulent. While many small-molecule lead compounds have been identified in whole-cell-based high-throughput screens (HTSs), only a few protein targets of these compounds are known; such knowledge is an important step to developing more potent and specific inhibitors. Evaluation of the efficacy of compounds in animal studies is ongoing. Some efforts involving the development of antibodies and vaccines that target the T3SSi are further along and include an antibody that is currently in phase II clinical trials. Continued research into these antivirulence therapies, used alone or in combination with traditional antibiotics, requires combined efforts from both pharmaceutical companies and academic labs.
    MeSH term(s) Animals ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Clinical Trials as Topic ; Gram-Negative Bacteria/drug effects ; Gram-Negative Bacterial Infections/drug therapy ; Humans ; Mice ; Type III Secretion Systems/metabolism ; Virulence
    Chemical Substances Anti-Bacterial Agents ; Type III Secretion Systems
    Language English
    Publishing date 2019-02-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ISSN 2324-6200
    ISSN (online) 2324-6200
    DOI 10.1128/ecosalplus.ESP-0032-2018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: New Age Strategies To Reconstruct Mucosal Tissue Colonization and Growth in Cell Culture Systems.

    Fasciano, Alyssa C / Mecsas, Joan / Isberg, Ralph R

    Microbiology spectrum

    2019  Volume 7, Issue 2

    Abstract: Over the past few decades, ...

    Abstract Over the past few decades,
    MeSH term(s) Animals ; Cell Culture Techniques/methods ; Host-Pathogen Interactions ; Humans ; Intestines/cytology ; Intestines/immunology ; Mucous Membrane/cytology ; Mucous Membrane/microbiology ; Organoids/cytology ; Organoids/microbiology ; Tissue Engineering/methods ; Tissue Scaffolds/microbiology ; Tropism
    Language English
    Publishing date 2019-02-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ISSN 2165-0497
    ISSN (online) 2165-0497
    DOI 10.1128/microbiolspec.BAI-0013-2019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Yersinia pseudotuberculosis YopH targets SKAP2-dependent and independent signaling pathways to block neutrophil antimicrobial mechanisms during infection.

    Shaban, Lamyaa / Nguyen, Giang T / Mecsas-Faxon, Benjamin D / Swanson, Kenneth D / Tan, Shumin / Mecsas, Joan

    PLoS pathogens

    2020  Volume 16, Issue 5, Page(s) e1008576

    Abstract: Yersinia suppress neutrophil responses by using a type 3 secretion system (T3SS) to inject 6-7 Yersinia effector proteins (Yops) effectors into their cytoplasm. YopH is a tyrosine phosphatase that causes dephosphorylation of the adaptor protein SKAP2, ... ...

    Abstract Yersinia suppress neutrophil responses by using a type 3 secretion system (T3SS) to inject 6-7 Yersinia effector proteins (Yops) effectors into their cytoplasm. YopH is a tyrosine phosphatase that causes dephosphorylation of the adaptor protein SKAP2, among other targets in neutrophils. SKAP2 functions in reactive oxygen species (ROS) production, phagocytosis, and integrin-mediated migration by neutrophils. Here we identify essential neutrophil functions targeted by YopH, and investigate how the interaction between YopH and SKAP2 influence Yersinia pseudotuberculosis (Yptb) survival in tissues. The growth defect of a ΔyopH mutant was restored in mice defective in the NADPH oxidase complex, demonstrating that YopH is critical for protecting Yptb from ROS during infection. The growth of a ΔyopH mutant was partially restored in Skap2-deficient (Skap2KO) mice compared to wild-type (WT) mice, while induction of neutropenia further enhanced the growth of the ΔyopH mutant in both WT and Skap2KO mice. YopH inhibited both ROS production and degranulation triggered via integrin receptor, G-protein coupled receptor (GPCR), and Fcγ receptor (FcγR) stimulation. SKAP2 was required for integrin receptor and GPCR-mediated ROS production, but dispensable for degranulation under all conditions tested. YopH blocked SKAP2-independent FcγR-stimulated phosphorylation of the proximal signaling proteins Syk, SLP-76, and PLCγ2, and the more distal signaling protein ERK1/2, while only ERK1/2 phosphorylation was dependent on SKAP2 following integrin receptor activation. These findings reveal that YopH prevents activation of both SKAP2-dependent and -independent neutrophilic defenses, uncouple integrin- and GPCR-dependent ROS production from FcγR responses based on their SKAP2 dependency, and show that SKAP2 is not required for degranulation.
    MeSH term(s) Animals ; Bacterial Outer Membrane Proteins/immunology ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/immunology ; MAP Kinase Signaling System/genetics ; MAP Kinase Signaling System/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Neutrophils/immunology ; Neutrophils/pathology ; Protein Tyrosine Phosphatases/immunology ; Reactive Oxygen Species/immunology ; Signal Transduction/genetics ; Signal Transduction/immunology ; Yersinia pseudotuberculosis/immunology ; Yersinia pseudotuberculosis/pathogenicity ; Yersinia pseudotuberculosis Infections/genetics ; Yersinia pseudotuberculosis Infections/immunology ; Yersinia pseudotuberculosis Infections/pathology
    Chemical Substances Bacterial Outer Membrane Proteins ; Intracellular Signaling Peptides and Proteins ; Reactive Oxygen Species ; src kinase associated phosphoprotein 2 ; Protein Tyrosine Phosphatases (EC 3.1.3.48) ; yopH protein, Yersinia (EC 3.1.3.48)
    Language English
    Publishing date 2020-05-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7366
    ISSN (online) 1553-7374
    ISSN 1553-7366
    DOI 10.1371/journal.ppat.1008576
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Klebsiella pneumoniae: Going on the Offense with a Strong Defense.

    Paczosa, Michelle K / Mecsas, Joan

    Microbiology and molecular biology reviews : MMBR

    2016  Volume 80, Issue 3, Page(s) 629–661

    Abstract: Klebsiella pneumoniae causes a wide range of infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Historically, K. pneumoniae has caused serious infection primarily in immunocompromised individuals, but the recent ...

    Abstract Klebsiella pneumoniae causes a wide range of infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Historically, K. pneumoniae has caused serious infection primarily in immunocompromised individuals, but the recent emergence and spread of hypervirulent strains have broadened the number of people susceptible to infections to include those who are healthy and immunosufficient. Furthermore, K. pneumoniae strains have become increasingly resistant to antibiotics, rendering infection by these strains very challenging to treat. The emergence of hypervirulent and antibiotic-resistant strains has driven a number of recent studies. Work has described the worldwide spread of one drug-resistant strain and a host defense axis, interleukin-17 (IL-17), that is important for controlling infection. Four factors, capsule, lipopolysaccharide, fimbriae, and siderophores, have been well studied and are important for virulence in at least one infection model. Several other factors have been less well characterized but are also important in at least one infection model. However, there is a significant amount of heterogeneity in K. pneumoniae strains, and not every factor plays the same critical role in all virulent Klebsiella strains. Recent studies have identified additional K. pneumoniae virulence factors and led to more insights about factors important for the growth of this pathogen at a variety of tissue sites. Many of these genes encode proteins that function in metabolism and the regulation of transcription. However, much work is left to be done in characterizing these newly discovered factors, understanding how infections differ between healthy and immunocompromised patients, and identifying attractive bacterial or host targets for treating these infections.
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Bacterial Capsules/genetics ; Bacterial Capsules/immunology ; Bacterial Capsules/metabolism ; Bacterial Outer Membrane Proteins/immunology ; Bacterial Outer Membrane Proteins/metabolism ; Drug Resistance, Multiple, Bacterial ; Fimbriae, Bacterial/genetics ; Fimbriae, Bacterial/metabolism ; Humans ; Immunocompromised Host/immunology ; Klebsiella Infections/microbiology ; Klebsiella Infections/pathology ; Klebsiella pneumoniae/drug effects ; Klebsiella pneumoniae/immunology ; Klebsiella pneumoniae/pathogenicity ; Lipopolysaccharides/metabolism ; Siderophores/genetics ; Virulence Factors/metabolism
    Chemical Substances Anti-Bacterial Agents ; Bacterial Outer Membrane Proteins ; Lipopolysaccharides ; Siderophores ; Virulence Factors
    Language English
    Publishing date 2016-09
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1376131-6
    ISSN 1098-5557 ; 1070-6275 ; 1092-2172
    ISSN (online) 1098-5557 ; 1070-6275
    ISSN 1092-2172
    DOI 10.1128/MMBR.00078-15
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Bacterial Secretion Systems: An Overview.

    Green, Erin R / Mecsas, Joan

    Microbiology spectrum

    2016  Volume 4, Issue 1

    Abstract: Bacterial pathogens utilize a multitude of methods to invade mammalian hosts, damage tissue sites, and thwart the immune system from responding. One essential component of these strategies for many bacterial pathogens is the secretion of proteins across ... ...

    Abstract Bacterial pathogens utilize a multitude of methods to invade mammalian hosts, damage tissue sites, and thwart the immune system from responding. One essential component of these strategies for many bacterial pathogens is the secretion of proteins across phospholipid membranes. Secreted proteins can play many roles in promoting bacterial virulence, from enhancing attachment to eukaryotic cells, to scavenging resources in an environmental niche, to directly intoxicating target cells and disrupting their functions. Many pathogens use dedicated protein secretion systems to secrete virulence factors from the cytosol of the bacteria into host cells or the host environment. In general, bacterial protein secretion apparatuses can be divided into classes, based on their structures, functions, and specificity. Some systems are conserved in all classes of bacteria and secrete a broad array of substrates, while others are only found in a small number of bacterial species and/or are specific to only one or a few proteins. In this chapter, we review the canonical features of several common bacterial protein secretion systems, as well as their roles in promoting the virulence of bacterial pathogens. Additionally, we address recent findings that indicate that the innate immune system of the host can detect and respond to the presence of protein secretion systems during mammalian infection.
    MeSH term(s) Animals ; Bacterial Secretion Systems ; Humans
    Chemical Substances Bacterial Secretion Systems
    Language English
    Publishing date 2016-03-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ISSN 2165-0497
    ISSN (online) 2165-0497
    DOI 10.1128/microbiolspec.VMBF-0012-2015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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