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Targeted control of pneumolysin production by a mobile genetic element in Streptococcus pneumoniae.
Stevens, Emily J; Morse, Daniel J; Bonini, Dora; Duggan, Seána; Brignoli, Tarcisio; Recker, Mario; Lees, John A; Croucher, Nicholas J; Bentley, Stephen; Wilson, Daniel J; Earle, Sarah G; Dixon, Robert; Nobbs, Angela; Jenkinson, Howard; van Opijnen, Tim; Thibault, Derek; Wilkinson, Oliver J; Dillingham, Mark S; Carlile, Simon; McLoughlin, Rachel M; Massey, Ruth C.
Afiliação
  • Stevens EJ; School of Cellular and Molecular Medicine, University of Bristol, Bristol, BS8 1TD, UK.
  • Morse DJ; School of Cellular and Molecular Medicine, University of Bristol, Bristol, BS8 1TD, UK.
  • Bonini D; School of Cellular and Molecular Medicine, University of Bristol, Bristol, BS8 1TD, UK.
  • Duggan S; School of Cellular and Molecular Medicine, University of Bristol, Bristol, BS8 1TD, UK.
  • Brignoli T; School of Cellular and Molecular Medicine, University of Bristol, Bristol, BS8 1TD, UK.
  • Recker M; Centre for Ecology and Conservation, University of Exeter, Penryn Campus, Exeter, TR10 9FE, UK.
  • Lees JA; Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
  • Croucher NJ; MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, St. Mary's Campus, Imperial College London, London, W2 1PG, UK.
  • Bentley S; MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, St. Mary's Campus, Imperial College London, London, W2 1PG, UK.
  • Wilson DJ; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
  • Earle SG; Big Data Institute, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
  • Dixon R; Big Data Institute, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
  • Nobbs A; Big Data Institute, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
  • Jenkinson H; Bristol Dental School, University of Bristol, Bristol, BS1 2LY, UK.
  • van Opijnen T; Bristol Dental School, University of Bristol, Bristol, BS1 2LY, UK.
  • Thibault D; Biology Department, Boston College, Chestnut Hill, MA, USA.
  • Wilkinson OJ; Biology Department, Boston College, Chestnut Hill, MA, USA.
  • Dillingham MS; DNA-Protein Interactions Unit, School of Biochemistry, University of Bristol, Bristol, BS8 1TD, UK.
  • Carlile S; DNA-Protein Interactions Unit, School of Biochemistry, University of Bristol, Bristol, BS8 1TD, UK.
  • McLoughlin RM; Host Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
  • Massey RC; Host Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
Microb Genom ; 8(4)2022 04.
Article em En | MEDLINE | ID: mdl-35416147
Streptococcus pneumoniae is a major human pathogen that can cause severe invasive diseases such as pneumonia, septicaemia and meningitis. Young children are at a particularly high risk, with an estimated 3-4 million cases of severe disease and between 300 000 and 500 000 deaths attributable to pneumococcal disease each year. The haemolytic toxin pneumolysin (Ply) is a primary virulence factor for this bacterium, yet despite its key role in pathogenesis, immune evasion and transmission, the regulation of Ply production is not well defined. Using a genome-wide association approach, we identified a large number of potential affectors of Ply activity, including a gene acquired horizontally on the antibiotic resistance-conferring Integrative and Conjugative Element (ICE) ICESp23FST81. This gene encodes a novel modular protein, ZomB, which has an N-terminal UvrD-like helicase domain followed by two Cas4-like domains with potent ATP-dependent nuclease activity. We found the regulatory effect of ZomB to be specific for the ply operon, potentially mediated by its high affinity for the BOX repeats encoded therein. Using a murine model of pneumococcal colonization, we further demonstrate that a ZomB mutant strain colonizes both the upper respiratory tract and lungs at higher levels when compared to the wild-type strain. While the antibiotic resistance-conferring aspects of ICESp23FST81 are often credited with contributing to the success of the S. pneumoniae lineages that acquire it, its ability to control the expression of a major virulence factor implicated in bacterial transmission is also likely to have played an important role.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Streptococcus pneumoniae / Estudo de Associação Genômica Ampla Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Streptococcus pneumoniae / Estudo de Associação Genômica Ampla Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article