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  1. Article ; Online: Drosophila versus Mycobacteria: A model for mycobacterial host-pathogen interactions.

    Marshall, Eleanor K P / Dionne, Marc S

    Molecular microbiology

    2021  Volume 117, Issue 3, Page(s) 600–609

    Abstract: Animal models have played an essential role in understanding the host-pathogen interactions of pathogenic mycobacteria, including the Mycobacterium tuberculosis and emerging nontuberculous mycobacteria (NTM) species such as M. avium and M. abscessus. ... ...

    Abstract Animal models have played an essential role in understanding the host-pathogen interactions of pathogenic mycobacteria, including the Mycobacterium tuberculosis and emerging nontuberculous mycobacteria (NTM) species such as M. avium and M. abscessus. Drosophila melanogaster has become a well-established model for the study of innate immunity and is increasingly being used as a tool to study host-pathogen interactions, in part due to its genetic tractability. The use of D. melanogaster has led to greater understanding of the role of the innate immune system in response to mycobacterial infection, including in vitro RNAi screens and in vivo studies. These studies have identified processes and host factors involved in mycobacterial infection, such as those required for cellular entry, those required to control or resist non-pathogenic mycobacteria, or factors that become dysregulated as a result of mycobacterial infection. Developments in genetic tools for manipulating mycobacterial genomes will allow for more detailed studies into how specific host and pathogen factors interact with one another by using D. melanogaster; however, the full potential of this model has not yet been reached. Here we provide an overview of how D. melanogaster has been used to study mycobacterial infection and discuss the current gaps in our understanding.
    MeSH term(s) Animals ; Drosophila ; Drosophila melanogaster ; Host-Pathogen Interactions ; Mycobacterium Infections ; Mycobacterium tuberculosis/genetics
    Language English
    Publishing date 2021-10-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 619315-8
    ISSN 1365-2958 ; 0950-382X
    ISSN (online) 1365-2958
    ISSN 0950-382X
    DOI 10.1111/mmi.14819
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Mycobacterium abscessus pathogenesis identified by phenogenomic analyses.

    Boeck, Lucas / Burbaud, Sophie / Skwark, Marcin / Pearson, Will H / Sangen, Jasper / Wuest, Andreas W / Marshall, Eleanor K P / Weimann, Aaron / Everall, Isobel / Bryant, Josephine M / Malhotra, Sony / Bannerman, Bridget P / Kierdorf, Katrin / Blundell, Tom L / Dionne, Marc S / Parkhill, Julian / Andres Floto, R

    Nature microbiology

    2022  Volume 7, Issue 9, Page(s) 1431–1441

    Abstract: The medical and scientific response to emerging and established pathogens is often severely hampered by ignorance of the genetic determinants of virulence, drug resistance and clinical outcomes that could be used to identify therapeutic drug targets and ... ...

    Abstract The medical and scientific response to emerging and established pathogens is often severely hampered by ignorance of the genetic determinants of virulence, drug resistance and clinical outcomes that could be used to identify therapeutic drug targets and forecast patient trajectories. Taking the newly emergent multidrug-resistant bacteria Mycobacterium abscessus as an example, we show that combining high-dimensional phenotyping with whole-genome sequencing in a phenogenomic analysis can rapidly reveal actionable systems-level insights into bacterial pathobiology. Through phenotyping of 331 clinical isolates, we discovered three distinct clusters of isolates, each with different virulence traits and associated with a different clinical outcome. We combined genome-wide association studies with proteome-wide computational structural modelling to define likely causal variants, and employed direct coupling analysis to identify co-evolving, and therefore potentially epistatic, gene networks. We then used in vivo CRISPR-based silencing to validate our findings and discover clinically relevant M. abscessus virulence factors including a secretion system, thus illustrating how phenogenomics can reveal critical pathways within emerging pathogenic bacteria.
    MeSH term(s) Genome, Bacterial ; Genome-Wide Association Study ; Humans ; Mycobacterium Infections, Nontuberculous ; Mycobacterium abscessus ; Virulence Factors
    Chemical Substances Virulence Factors
    Language English
    Publishing date 2022-08-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2058-5276
    ISSN (online) 2058-5276
    DOI 10.1038/s41564-022-01204-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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