Publications

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
    Switzer A, Burchell L, McQuail J, Wigneshweraraj Set al., 2020,

    The adaptive response to long-term nitrogen starvation in Escherichia coli requires the breakdown of allantoin.

    , Journal of Bacteriology, Vol: 202, Pages: 1-11, ISSN: 0021-9193

    Bacteria initially respond to nutrient starvation by eliciting large-scale transcriptional changes. The accompanying changes in gene expression and metabolism allow the bacterial cells to effectively adapt to the nutrient starved state. How the transcriptome subsequently changes as nutrient starvation ensues is not well understood. We used nitrogen (N) starvation as a model nutrient starvation condition to study the transcriptional changes in Escherichia coli experiencing long-term N starvation. The results reveal that the transcriptome of N starved E. coli undergoes changes that are required to maximise chances of viability and to effectively recover growth when N starvation conditions become alleviated. We further reveal that, over time, N starved E. coli cells rely on the degradation of allantoin for optimal growth recovery when N becomes replenished. This study provides insights into the temporally coordinated adaptive responses that occur in E. coli experiencing sustained N starvation.IMPORTANCE Bacteria in their natural environments seldom encounter conditions that support continuous growth. Hence, many bacteria spend the majority of their time in states of little or no growth due to starvation of essential nutrients. To cope with prolonged periods of nutrient starvation, bacteria have evolved several strategies, primarily manifesting themselves through changes in how the information in their genes is accessed. How these coping strategies change over time under nutrient starvation is not well understood and this knowledge is not only important to broaden our understanding of bacterial cell function, but also to potentially find ways to manage harmful bacteria. This study provides insights into how nitrogen starved Escherichia coli bacteria rely on different genes during long term nitrogen starvation.
  • Journal article
    Kamal F, Glanville N, Xia W, Bakhsoliani E, Aniscenko J, Bartlett NW, Edwards MR, Johnston SL, Singanayagam Aet al., 2020,

    Beclomethasone has lesser suppressive effects on inflammation and anti-bacterial immunity than Fluticasone or Budesonide in experimental infection models.

    , Chest, Vol: 158, Pages: 947-951, ISSN: 0012-3692
  • Journal article
    McQuail J, Switzer A, Burchell L, Wigneshweraraj Set al., 2020,

    The RNA-binding protein Hfq assembles into foci-like structures in nitrogen starved Escherichia coli

    , Journal of Biological Chemistry, Vol: 295, Pages: 12355-12367, ISSN: 0021-9258

    The initial adaptive responses to nutrient depletion in bacteria often occur at the level of gene expression. Hfq is an RNA-binding protein present in diverse bacterial lineages and contributes to many different aspects of RNA metabolism during gene expression. Using photoactivated localization microscopy (PALM) and single molecule tracking, we demonstrate that Hfq forms a distinct and reversible focus-like structure in Escherichia coli specifically experiencing long-term nitrogen (N) starvation. Using the ability of T7 phage to replicate in N-starved bacteria as a biological probe of E. coli cell function during N starvation, we demonstrate that Hfq foci have a role in the adaptive response of E. coli to long-term N starvation. We further show that Hfq foci formation does not depend on gene expression once N starvation has set in and occurs independently of the transcription factor N-regulatory protein C (NtrC), that activates the initial adaptive response to N starvation in E. coli These results serve as a paradigm to demonstrate that bacterial adaptation to long-term nutrient starvation can be spatiotemporally coordinated and can occur independently of de novo gene expression during starvation.
  • Journal article
    Rapun-Araiz B, Haag AF, De Cesare V, Gil C, Dorado-Morales P, Penades JR, Lasa Iet al., 2020,

    Systematic reconstruction of the complete two-component sensorial network in staphylococcus aureus.

    , mSystems, Vol: 5, Pages: 1-16, ISSN: 2379-5077

    In bacteria, adaptation to changes in the environment is mainly controlled through two-component signal transduction systems (TCSs). Most bacteria contain dozens of TCSs, each of them responsible for sensing a different range of signals and controlling the expression of a repertoire of target genes (regulon). Over the years, identification of the regulon controlled by each individual TCS in different bacteria has been a recurrent question. However, limitations associated with the classical approaches used have left our knowledge far from complete. In this report, using a pioneering approach in which a strain devoid of the complete nonessential TCS network was systematically complemented with the constitutively active form of each response regulator, we have reconstituted the regulon of each TCS of S. aureus in the absence of interference between members of the family. Transcriptome sequencing (RNA-Seq) and proteomics allowed us to determine the size, complexity, and insulation of each regulon and to identify the genes regulated exclusively by one or many TCSs. This gain-of-function strategy provides the first description of the complete TCS regulon in a living cell, which we expect will be useful to understand the pathobiology of this important pathogen.IMPORTANCE Bacteria are able to sense environmental conditions and respond accordingly. Their sensorial system relies on pairs of sensory and regulatory proteins, known as two-component systems (TCSs). The majority of bacteria contain dozens of TCSs, each of them responsible for sensing and responding to a different range of signals. Traditionally, the function of each TCS has been determined by analyzing the changes in gene expression caused by the absence of individual TCSs. Here, we used a bacterial strain deprived of the complete TC sensorial system to introduce, one by one, the active form of every TCS. This gain-of-function strategy allowed us to identify the changes in gene expression conferred by each TCS wit
  • Journal article
    Vincent CM, Dionne MS, 2020,

    Disparate regulation of <i>imd</i> drives sex differences in infection pathology in <i>Drosophila melanogaster</i>

    <jats:title>Abstract</jats:title><jats:p>Male and female animals exhibit differences in infection outcomes. One possible source of sexually dimorphic immunity is sex-specific costs of immune activity or pathology, but little is known about the independent effects of immune-induced versus microbe-induced pathology, and whether these may differ for the sexes. Here, through measuring metabolic and physiological outputs in wild-type and immune-compromised <jats:italic>Drosophila melanogaster</jats:italic>, we test whether the sexes are differentially impacted by these various sources of pathology and identify a critical regulator of this difference. We find that the sexes exhibit differential immune activity but similar bacteria-derived metabolic pathology. We show that female-specific immune-inducible expression of <jats:italic>PGRP-LB</jats:italic>, a negative regulator of the Imd pathway, enables females to reduce immune activity in response to reductions in bacterial numbers. In the absence of <jats:italic>PGRP-LB</jats:italic>, females are more resistant of infection, confirming the functional importance of this regulation and suggesting that female-biased immune restriction comes at a cost.</jats:p>
  • Journal article
    Fisch D, Clough B, Domart M-C, Encheva V, Bando H, Snijders AP, Collinson LM, Yamamoto M, Shenoy AR, Frickel E-Met al., 2020,

    Human GBP1 differentially targets salmonella and toxoplasma to license recognition of microbial ligands and caspase-mediated death

    , Cell Reports, Vol: 32, Pages: 1-22, ISSN: 2211-1247

    Interferon-inducible guanylate-binding proteins (GBPs) promote cell-intrinsic defense through host cell death. GBPs target pathogens and pathogen-containing vacuoles and promote membrane disruption for release of microbial molecules that activate inflammasomes. GBP1 mediates pyroptosis or atypical apoptosis of Salmonella Typhimurium (STm)- or Toxoplasma gondii (Tg)- infected human macrophages, respectively. The pathogen-proximal detection-mechanisms of GBP1 remain poorly understood, as humans lack functional immunity-related GTPases (IRGs) that assist murine Gbps. Here, we establish that GBP1 promotes the lysis of Tg-containing vacuoles and parasite plasma membranes, releasing Tg-DNA. In contrast, we show GBP1 targets cytosolic STm and recruits caspase-4 to the bacterial surface for its activation by lipopolysaccharide (LPS), but does not contribute to bacterial vacuole escape. Caspase-1 cleaves and inactivates GBP1, and a cleavage-deficient GBP1D192E mutant increases caspase-4-driven pyroptosis due to the absence of feedback inhibition. Our studies elucidate microbe-specific roles of GBP1 in infection detection and its triggering of the assembly of divergent caspase signaling platforms.
  • Journal article
    Ritchie AI, Singanayagam A, 2020,

    Metagenomic Characterization of the Respiratory Microbiome A Piece de Resistance

    , AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 202, Pages: 321-322, ISSN: 1073-449X
  • Journal article
    Pataia V, McIlvride S, Papacleovoulou G, Ovadia C, McDonald JAK, Wahlstrom A, Jansen E, Adorini L, Shapiro D, Marchesi JR, Marschall H-U, Williamson Cet al., 2020,

    Obeticholic acid improves fetal bile acid profile in a mouse model of gestational hypercholanemia

    , AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, Vol: 319, Pages: G197-G211, ISSN: 0193-1857
  • Journal article
    Ding NS, McDonald JAK, Perdones-Montero A, Rees DN, Adegbola SO, Misra R, Hendy P, Penez L, Marchesi JR, Holmes E, Sarafian MH, Hart ALet al., 2020,

    Metabonomics and the Gut Microbiome Associated With Primary Response to Anti-TNF Therapy in Crohn's Disease

    , JOURNAL OF CROHNS & COLITIS, Vol: 14, Pages: 1090-1102, ISSN: 1873-9946
  • Journal article
    Murphy P, Xu Y, Rouse SL, Jaffray EG, Plechanovova A, Matthews SJ, Carlos Penedo J, Hay RTet al., 2020,

    Functional 3D architecture in an intrinsically disordered E3 ligase domain facilitates ubiquitin transfer

    , NATURE COMMUNICATIONS, Vol: 11, ISSN: 2041-1723

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://wwwtest.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=15&respub-action=search.html Current Millis: 1759601318493 Current Time: Sat Oct 04 19:08:38 BST 2025