Search or filter publications

Filter by type:

Filter by publication type

Filter by year:

to

Results

  • Showing results for:
  • Reset all filters

Search results

  • Journal article
    Fillol-Salom A, Rostøl JT, Ojiogu AD, Chen J, Douce G, Humphrey S, Penadés JRet al., 2022,

    Bacteriophages benefit from mobilizing pathogenicity islands encoding immune systems against competitors

    , Cell, Vol: 185, Pages: 3248-3262.e20, ISSN: 0092-8674

    Bacteria encode sophisticated anti-phage systems that are diverse and versatile and display high genetic mobility. How this variability and mobility occurs remains largely unknown. Here, we demonstrate that a widespread family of pathogenicity islands, the phage-inducible chromosomal islands (PICIs), carry an impressive arsenal of defense mechanisms, which can be disseminated intra- and inter-generically by helper phages. These defense systems provide broad immunity, blocking not only phage reproduction, but also plasmid and non-cognate PICI transfer. Our results demonstrate that phages can mobilize PICI-encoded immunity systems to use them against other mobile genetic elements, which compete with the phages for the same bacterial hosts. Therefore, despite the cost, mobilization of PICIs may be beneficial for phages, PICIs, and bacteria in nature. Our results suggest that PICIs are important players controlling horizontal gene transfer and that PICIs and phages establish mutualistic interactions that drive bacterial ecology and evolution.

  • Journal article
    Farne H, Lin L, Jackson D, Rattray M, Simpson A, Custovic A, Joshi S, Wilson P, Williamson R, Edwards M, Singanayagam A, Johnston Set al., 2022,

    In vivo bronchial epithelial interferon responses are augmented in asthma on day 4 following experimental rhinovirus infection

    , Thorax, Vol: 77, Pages: 929-932, ISSN: 0040-6376

    Despite good evidence of impaired innate antiviral responses in asthma, trials of inhaled interferon-β given during exacerbations showed only modest benefits in moderate/severe asthma. Using human experimental rhinovirus infection, we observe robust in vivo induction of bronchial epithelial interferon response genes four days after virus inoculation in 25 subjects with asthma but not 11 control subjects. This signature correlated with virus loads and lower respiratory symptoms. Our data indicate that the in vivo innate antiviral response is dysregulated in asthma and open up the potential that prophylactic rather than therapeutic interferon therapy may have greater clinical benefit.

  • Journal article
    Wadhawan A, Simoes da Silva CJ, Nunes CD, Edwards AM, Dionne MSet al., 2022,

    <i>E. faecalis</i>acquires resistance to antimicrobials and insect immunity via common mechanisms

    <jats:title>Summary</jats:title><jats:p><jats:italic>Enterococcus faecalis</jats:italic>is a normal member of the gut microbiota and an opportunistic pathogen of many animals, including mammals, birds, and insects. It is a common cause of nosocomial infections, and is particularly troublesome due to extensive intrinsic and acquired antimicrobial resistance. Using experimental evolution, we generated<jats:italic>Drosophila</jats:italic>-adapted<jats:italic>E. faecalis</jats:italic>strains, which exhibited immune resistance, resulting in increased<jats:italic>in vivo</jats:italic>growth and virulence. Resistance was characterised by mutations in bacterial pathways responsive to cell envelope stress.<jats:italic>Drosophila</jats:italic>-adapted strains exhibited changes in sensitivity to relevant antimicrobials, including daptomycin and vancomycin. Evolved daptomycin-resistant strains harboured mutations in the same signalling systems, with some strains showing increased virulence similar to<jats:italic>Drosophila</jats:italic>-adapted strains. Our results show that common mechanisms provide a route to resistance to both antimicrobials and host immunity in<jats:italic>E. faecalis</jats:italic>and demonstrate that the selection and emergence of antibiotic resistance<jats:italic>in vivo</jats:italic>does not require antibiotic exposure.</jats:p><jats:sec><jats:title>One sentence summary</jats:title><jats:p>Host interaction can promote antimicrobial resistance and antimicrobial treatment can promote virulence in<jats:italic>E. faecalis</jats:italic>.</jats:p></jats:sec>

  • Journal article
    Ledger EVK, Edwards AM, 2022,

    Growth arrest of <i>Staphylococcus aureus</i> induces daptomycin tolerance via cell wall remodelling

    <jats:title>Abstract</jats:title><jats:p>Almost all bactericidal drugs require bacterial replication and/or metabolic activity for their killing activity. When these processes are inhibited by bacteriostatic antibiotics, bacterial killing is significantly reduced. One notable exception is the lipopeptide antibiotic daptomycin, which has been reported to efficiently kill non-dividing bacteria. However, these studies employed only brief periods of growth arrest. We found that a bacteriostatic concentration of the protein synthesis inhibitor tetracycline led to a time-dependent induction of daptomycin tolerance in <jats:italic>S. aureus</jats:italic>, with <jats:sup>~</jats:sup>100,000-fold increase in survival after 16 h growth arrest relative to exponential phase bacteria. Daptomycin tolerance required glucose and was associated with increased production of the cell wall polymers peptidoglycan and wall-teichoic acids. However, whilst accumulation of peptidoglycan was required for daptomycin tolerance, only a low abundance of wall teichoic acid was necessary. Therefore, whilst tolerance to most antibiotics occurs passively due to a lack of metabolic activity and/or replication, daptomycin tolerance arises via active cell wall remodelling.</jats:p>

  • Journal article
    Singh S, Wilksch JJ, Dunstan RA, Mularski A, Wang N, Hocking D, Jebeli L, Cao H, Clements A, Jenney AWJ, Lithgow T, Strugnell RAet al., 2022,

    LPS O Antigen Plays a Key Role in Klebsiella pneumoniae Capsule Retention

    , MICROBIOLOGY SPECTRUM, ISSN: 2165-0497
  • Journal article
    Hamilton C, Olona A, Leishman S, MacDonald-Ramsahai K, Cockcroft S, Larrouy-Maumus G, Anand Pet al., 2022,

    NLRP3 inflammasome priming and activation are regulated by a phosphatidylinositol-dependent mechanism

    , ImmunoHorizons, Vol: 6, ISSN: 2573-7732

    Imbalance in lipid homeostasis is associated with discrepancies in immune signaling and is tightly linked to metabolic disorders. The diverse ways in which lipids impact immune signaling, however, remain ambiguous. The phospholipid phosphatidylinositol (PI), which is implicated in numerous immune disorders, is chiefly defined by its phosphorylation status. By contrast, the significance of the two fatty acid chains attached to the PI remains unknown. Here, by employing a mass-spectrometry-based assay, we demonstrate a role for PI acyl group chains in regulating both the priming and activation steps of the NLRP3 inflammasome in mouse macrophages. In response to NLRP3 stimuli, cells deficient in ABC transporter ABCB1, which effluxes lipid derivatives, revealed defective inflammasome activation. Mechanistically, Abcb1-deficiency shifted the total PI configuration exhibiting a reduced ratio of short-chain to long-chain PI acyl lipids. Consequently, Abcb1-deficiency initiated the rapid degradation of TIRAP, the TLR adaptor protein which binds PI (4,5)-bisphosphate, resulting in defective TLR-dependent signaling, and thus NLRP3 expression. Moreover, this accompanied increased NLRP3 phosphorylation at the Ser291 position and contributed to blunted inflammasome activation. Exogenously supplementing WT cells with linoleic acid, but not arachidonic acid, reconfigured PI acyl chains. Accordingly, linoleic acid supplementation increased TIRAP degradation, elevated NLRP3 phosphorylation, and abrogated inflammasome activation. Furthermore, NLRP3 Ser291 phosphorylation was dependent on prostaglandin E2-induced protein kinase A signaling as pharmacological inhibition of this pathway in linoleic acid-enriched cells dephosphorylated NLRP3. Altogether, our study reveals a novel metabolic-inflammatory circuit which contributes to calibrating immune responses.

  • Journal article
    Larrouy-Maumus G, Thomson M, Nunta K, Liu Y, Fernandes N, Williams R, garza-garcia Aet al., 2022,

    Expression of a novel mycobacterial phosphodiesterase successfully lowers cAMP levels resulting in reduced tolerance to cell wall-targeting antimicrobials

    , Journal of Biological Chemistry, Vol: 298, ISSN: 0021-9258

    Antimicrobial tolerance, the ability to survive exposure to antimicrobials via transient nonspecific means, promotes the development of antimicrobial resistance (AMR). The study of the molecular mechanisms that result in antimicrobial tolerance is therefore essential for the understanding of AMR. In gram-negative bacteria, the second messenger molecule 3’,5’-cyclic adenosine monophosphate (cAMP) has been previously shown to be involved in AMR. In mycobacteria, however, the role of cAMP in antimicrobial tolerance has been difficult to probe due to its particular complexity. In order to address this difficulty, here, through an unbiased biochemical approaches consisting in the fractionation of clear protein lysate from a mycobacterial strain deleted for the known cAMP phosphodiesterase (Rv0805c) combined with mass spectrometry techniques, we identified a novel cyclic nucleotide-degrading phosphodiesterase enzyme (Rv1339) and developed a system to significantly decrease intracellular cAMP levels through plasmid expression of Rv1339 using the constitutive expression system, pVV16. In Mycobacterium smegmatis mc2155, we demonstrate that recombinant expression of Rv1339 reduced cAMP levels 3-fold and resulted in altered gene expression, impaired bioenergetics and a disruption in peptidoglycan biosynthesis leading to decreased tolerance to antimicrobials that target cell wall synthesis such as ethambutol, D-cycloserine and vancomycin. This work increases our understanding of the role of cAMP in mycobacterial antimicrobial tolerance and our observations suggest that nucleotide signaling may represent a new target for the development of antimicrobial therapies.

  • Journal article
    Periselneris J, Turner CT, Ercoli G, Szylar G, Weight CM, Thurston T, Whelan M, Tomlinson G, Noursadeghi M, Brown Jet al., 2022,

    Pneumolysin suppresses the initial macrophage pro-inflammatory response to Streptococcus pneumoniae

    , IMMUNOLOGY, Vol: 167, Pages: 413-427, ISSN: 0019-2805
  • Journal article
    Chaukimath P, Frankel G, Visweswariah SS, 2022,

    The metabolic impact of bacterial infection in the gut

    , FEBS JOURNAL, ISSN: 1742-464X
  • Journal article
    Zhang K, Li S, Wang Y, Wang Z, Mulvenna N, Yang H, Zhang P, Chen H, Li Y, Wang H, Gao Y, Wigneshweraraj S, Matthews S, Zhang K, Liu Bet al., 2022,

    Bacteriophage protein PEIP is a potent Bacillus subtilis enolase inhibitor

    , CELL REPORTS, Vol: 40, ISSN: 2211-1247

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://www.imperial.ac.uk:80/respub/WEB-INF/jsp/search-t4-html.jsp Request URI: /respub/WEB-INF/jsp/search-t4-html.jsp Query String: id=288&limit=10&page=3&respub-action=search.html Current Millis: 1675364334039 Current Time: Thu Feb 02 18:58:54 GMT 2023