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  • Journal article
    Lee WWY, Mattock J, Greig DR, Langridge GC, Baker D, Bloomfield S, Mather AE, Wain JR, Edwards AM, Hartman H, Dallman TJ, Chattaway MA, Nair Set al., 2021,

    Characterization of a pESI- like plasmid and analysis of multidrug-resistant Salmonella enterica Infantis isolates in England and Wales

    , Microbial Genomics, Vol: 7, Pages: 1-11, ISSN: 2057-5858

    Salmonella enterica serovar Infantis is the fifth most common Salmonella serovar isolated in England and Wales. Epidemiological, genotyping and antimicrobial-resistance data for S. enterica Infantis isolates were used to analyse English and Welsh demographics over a 5 year period. Travel cases associated with S. enterica Infantis were mainly from Asia, followed by cases from Europe and North America. Since 2000, increasing numbers of S. enterica Infantis had multidrug resistance determinants harboured on a large plasmid termed ‘plasmid of emerging S. enterica Infantis’ (pESI). Between 2013 and 2018, 42 S. enterica Infantis isolates were isolated from humans and food that harboured resistance determinants to multiple antimicrobial classes present on a pESI-like plasmid, including extended-spectrum β-lactamases (ESBLs; blaCTX-M-65). Nanopore sequencing of an ESBL-producing human S. enterica Infantis isolate indicated the presence of two regions on an IncFIB pESI-like plasmid harbouring multiple resistance genes. Phylogenetic analysis of the English and Welsh S. enterica Infantis population indicated that the majority of multidrug-resistant isolates harbouring the pESI-like plasmid belonged to a single clade maintained within the population. The blaCTX-M-65 ESBL isolates first isolated in 2013 comprise a lineage within this clade, which was mainly associated with South America. Our data, therefore, show the emergence of a stable resistant clone that has been in circulation for some time in the human population in England and Wales, highlighting the necessity of monitoring resistance in this serovar.

  • Journal article
    Armstrong-James D, 2021,

    Future Directions for Clinical Respiratory Fungal Research

    , MYCOPATHOLOGIA, Vol: 186, Pages: 685-696, ISSN: 0301-486X
  • Journal article
    Panwar RB, Sequeira RP, Clarke TB, 2021,

    Microbiota-mediated protection against antibiotic-resistant pathogens

    , GENES AND IMMUNITY, Vol: 22, Pages: 255-267, ISSN: 1466-4879
  • Journal article
    Periselneris J, Schelenz S, Loebinger M, Macedo P, Adhya Z, Armstrong-James D, Kelleher WPet al., 2021,

    Bronchiectasis severity correlates with outcome in patients with primary antibody deficiency

    , THORAX, Vol: 76, Pages: 1036-1039, ISSN: 0040-6376
  • Journal article
    Haag AF, Podkowik M, Ibarra-Chavez R, Gallego del Sol F, Ram G, Chen J, Marina A, Novick RP, Penades JRet al., 2021,

    A regulatory cascade controls <i>Staphylococcus aureus</i> pathogenicity island activation

    , NATURE MICROBIOLOGY, Vol: 6, Pages: 1300-+, ISSN: 2058-5276
  • Journal article
    Chatterjee S, Choi A, Frankel G, 2021,

    A systematic review of Sec24 cargo interactome

    , Traffic, Vol: 22, Pages: 412-424, ISSN: 1398-9219

    Endoplasmic reticulum (ER)-to-Golgi trafficking is an essential and highly conserved cellular process. The coat protein complex-II (COPII) arm of the trafficking machinery incorporates a wide array of cargo proteins into vesicles through direct or indirect interactions with Sec24, the principal subunit of the COPII coat. Approximately one-third of all mammalian proteins rely on the COPII mediated secretory pathway for membrane insertion or secretion. There are four mammalian Sec24 paralogs and three yeast Sec24 paralogs with emerging evidence of paralog-specific cargo interaction motifs. Furthermore, individual paralogs also differ in their affinity for a subset of sorting motifs present on cargo proteins. As with many aspects of protein trafficking, we lack a systematic and thorough understanding of the interaction of Sec24 with cargoes. This systematic review focuses on the current knowledge of cargo binding to both yeast and mammalian Sec24 paralogs and their ER export motifs. The analyses show that Sec24 paralog specificity of cargo (and cargo receptors) range from exclusive paralog dependence or preference to partial redundancy. Wealso discuss how the Sec24 secretion system is hijacked by viral (e.g., VSV-G, Hepatitis B envelope protein) and bacterial (e.g., the enteropathogenic E. coli type III secretion system effector NleA/EspI) pathogens.

  • Journal article
    Rose S, Beckwith EJ, Burmester C, May RC, Dionne MS, Rezaval Cet al., 2021,

    Pre-copulatory reproductive behaviours are preserved in <i>Drosophila melanogaster</i> infected with bacteria

    <jats:title>Abstract</jats:title><jats:p>Reproduction and immunity are crucial traits that determine an animal’s fitness. Terminal investment hypothesis predicts that reproductive investment should increase in the face of a mortality risk caused by infection. However, due to competitive allocation of energetic resources, individuals fighting infections are expected to decrease reproductive efforts. While there is evidence for both hypotheses, the factors that determine the choice between these strategies are poorly understood. Here, we assess the impact of bacterial infection on pre-copulatory behaviours in the fruit fly <jats:italic>Drosophila melanogaster</jats:italic>. We found that male flies infected with six different bacteria, including pathogenic and non-pathogenic strains, show no significant differences in courtship intensity and mating success. Similarly, bacterial infections did not affect sexual receptivity in female flies. Our data suggest that pre-copulatory reproductive behaviours remain preserved in infected animals, despite the huge metabolic cost of infection.</jats:p>

  • Journal article
    Kelsall IR, McCrory EH, Xu Y, Scudamore CL, Nanda SK, Mancebo-Gamella P, Wood NT, Knebel A, Matthews SJ, Cohen Pet al., 2021,

    HOIL-1-catalysed ubiquitylation of unbranched glucosaccharides and its activation by ubiquitin oligomers

    <jats:title>Abstract</jats:title><jats:p>HOIL-1, a component of the Linear Ubiquitin Assembly Complex (LUBAC), ubiquitylates serine and threonine residues in proteins, forming ester bonds (Kelsall et al, 2019, PNAS 116, 13293-13298). Here we report that mice expressing the E3 ligase-inactive HOIL-1[C458S] mutant accumulate polyglucosan in brain, cardiac muscle and other organs, indicating that HOIL-1’s E3 ligase activity is essential to prevent these toxic polysaccharide deposits from accumulating. We found that HOIL-1 monoubiquitylates glycogen and α1:4-linked maltoheptaose <jats:italic>in vitro</jats:italic> and identify the C6 hydroxyl moiety of glucose as the site of ester-linked ubiquitylation. The HOIL-1-catalysed monoubiquitylation of maltoheptaose was accelerated &gt;100-fold by Met1-linked or Lys63-linked ubiquitin oligomers, which interact with the catalytic RBR domain of HOIL-1. HOIL-1 also transferred preformed ubiquitin oligomers to maltoheptaose <jats:italic>en bloc</jats:italic>, producing polyubiquitylated maltoheptaose in one catalytic step. The Sharpin and HOIP components of LUBAC, but not HOIL-1, bound to amylose resin <jats:italic>in vitro</jats:italic>, suggesting a potential function in targeting HOIL-1 to unbranched glucosaccharides in cells. We suggest that monoubiquitylation of unbranched glucosaccharides may initiate their removal by glycophagy to prevent precipitation as polyglucosan.</jats:p>

  • Journal article
    Shah A, Armstrong-James D, Chotirmall SH, 2021,

    Respiratory mycoses: a call to action to recognize, educate and invest.

    , Mycopathologia, Vol: 186, Pages: 569-573, ISSN: 0301-486X
  • Journal article
    Clarke RS, Ha KP, Edwards AM, 2021,

    RexAB promotes the survival of staphylococcus aureus exposed to multiple classes of antibiotics

    , Antimicrobial Agents and Chemotherapy, Vol: 65, Pages: 1-13, ISSN: 0066-4804

    Antibiotics inhibit essential bacterial processes, resulting in arrest of growth and, in some cases, cell death. Many antibiotics are also reported to trigger endogenous production of reactive oxygen species (ROS), which damage DNA, leading to induction of the mutagenic SOS response associated with the emergence of drug resistance. However, the type of DNA damage that arises and how this triggers the SOS response are largely unclear. We found that several different classes of antibiotic triggered dose-dependent induction of the SOS response in Staphylococcus aureus, indicative of DNA damage, including some bacteriostatic drugs. The SOS response was heterogenous and varied in magnitude between strains and antibiotics. However, in many cases, full induction of the SOS response was dependent upon the RexAB helicase/nuclease complex, which processes DNA double-strand breaks to produce single-stranded DNA and facilitate RecA nucleoprotein filament formation. The importance of RexAB in repair of DNA was confirmed by measuring bacterial survival during antibiotic exposure, with most drugs having significantly greater bactericidal activity against rexB mutants than against wild-type strains. For some, but not all, antibiotics there was no difference in bactericidal activity between wild type and rexB mutant under anaerobic conditions, indicative of a role for reactive oxygen species in mediating DNA damage. Taken together, this work confirms previous observations that several classes of antibiotics cause DNA damage in S. aureus and extends them by showing that processing of DNA double-strand breaks by RexAB is a major trigger of the mutagenic SOS response and promotes bacterial survival.

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