CdtR Regulates TcdA and TcdB Production in Clostridium difficile
Publication Date
July 14, 2016
Journal
PLOS Pathogens
Authors
Shelley A. Lyon, Melanie L. Hutton, Julian I. Rood, Jackie K. Cheung, et al
Volume
12
Issue
7
Pages
e1005758
DOI
https://dx.plos.org/10.1371/journal.ppat.1005758
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1005758
Web of Science
000383366400038
Scopus
84980583253
Mendeley
http://www.mendeley.com/research/cdtr-regulates-tcda-tcdb-production-clostridium-difficile
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Mendeley | Further Information

{"title"=>"CdtR Regulates TcdA and TcdB Production in Clostridium difficile", "type"=>"journal", "authors"=>[{"first_name"=>"Shelley A.", "last_name"=>"Lyon", "scopus_author_id"=>"36868066200"}, {"first_name"=>"Melanie L.", "last_name"=>"Hutton", "scopus_author_id"=>"36104288200"}, {"first_name"=>"Julian I.", "last_name"=>"Rood", "scopus_author_id"=>"55791822900"}, {"first_name"=>"Jackie K.", "last_name"=>"Cheung", "scopus_author_id"=>"7202072298"}, {"first_name"=>"Dena", "last_name"=>"Lyras", "scopus_author_id"=>"6701678150"}], "year"=>2016, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537374", "scopus"=>"2-s2.0-84982924058", "pui"=>"611582090", "doi"=>"10.1371/journal.ppat.1005758", "isbn"=>"1553-7374 (Electronic)\r1553-7366 (Linking)", "sgr"=>"84982924058", "pmid"=>"27414650"}, "id"=>"f33b07b7-b0fa-3e9d-869a-93d00afa0ef7", "abstract"=>"Clostridium difficile is a global health burden and the leading cause of antibiotic-associated diarrhoea worldwide, causing severe gastrointestinal disease and death. Three well charac- terised toxins are encoded by this bacterium in two genetic loci, specifically, TcdB (toxin B) and TcdA (toxin A) in the Pathogenicity Locus (PaLoc) and binary toxin (CDT) in the geno- mically distinct CDT locus (CdtLoc). Toxin production is controlled by regulators specific to each locus. The orphan response regulator, CdtR, encoded within the CdtLoc, up-regulates CDT production. Until now there has been no suggestion that CdtR influences TcdA and TcdB production since it is not carried by all PaLoc-containing strains and CdtLoc is not linked genetically to PaLoc. Here we show that, in addition to CDT, CdtR regulates TcdA and TcdB production but that this effect is strain dependent. Of clinical relevance, CdtR increased the production of TcdA, TcdB and CDT in two epidemic ribotype 027 human strains, modulating their virulence in a mouse infection model. Strains traditionally from ani- mal lineages, notably ribotype 078 strains, are increasingly being isolated from humans and their genetic and phenotypic analysis is critical for future studies on this important pathogen. Here we show that CdtR-mediated toxin regulation did not occur in other strain back- grounds, including a ribotype 078 animal strain. The finding that toxin gene regulation is strain dependent highlights the regulatory diversity between C. difficile isolates and the importance of studying virulence regulation in diverse lineages and clinically relevant strains. Our work provides the first evidence that TcdA, TcdB and CDT production is linked by a common regulatory mechanism and that CdtR may act as a global regulator of viru- lence in epidemic 027 strains. Author", "link"=>"http://www.mendeley.com/research/cdtr-regulates-tcda-tcdb-production-clostridium-difficile", "reader_count"=>24, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>3, "Researcher"=>2, "Student > Ph. D. Student"=>8, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>3, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>3, "Researcher"=>2, "Student > Ph. D. Student"=>8, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>3, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>12, "Medicine and Dentistry"=>2, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>3}}, "group_count"=>0}

Scopus | Further Information

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