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Cytotoxic and pathogenic properties of Klebsiella oxytoca isolated from laboratory animals.
Darby, Alison; Lertpiriyapong, Kvin; Sarkar, Ujjal; Seneviratne, Uthpala; Park, Danny S; Gamazon, Eric R; Batchelder, Chara; Cheung, Cheryl; Buckley, Ellen M; Taylor, Nancy S; Shen, Zeli; Tannenbaum, Steven R; Wishnok, John S; Fox, James G.
Afiliação
  • Darby A; Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
  • Lertpiriyapong K; Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
  • Sarkar U; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge. Massachusetts, United States of America.
  • Seneviratne U; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge. Massachusetts, United States of America.
  • Park DS; Pharmaceutical Sciences and Pharmacogenomics Graduate Program, University of California, San Francisco, California, United States of America.
  • Gamazon ER; Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, Illinois, United States of America.
  • Batchelder C; Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
  • Cheung C; Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
  • Buckley EM; Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
  • Taylor NS; Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
  • Shen Z; Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
  • Tannenbaum SR; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge. Massachusetts, United States of America; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
  • Wishnok JS; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge. Massachusetts, United States of America.
  • Fox JG; Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge. Massachusetts, United States of America.
PLoS One ; 9(7): e100542, 2014.
Article em En | MEDLINE | ID: mdl-25057966
ABSTRACT
Klebsiella oxytoca is an opportunistic pathogen implicated in various clinical diseases in animals and humans. Studies suggest that in humans K. oxytoca exerts its pathogenicity in part through a cytotoxin. However, cytotoxin production in animal isolates of K. oxytoca and its pathogenic properties have not been characterized. Furthermore, neither the identity of the toxin nor a complete repertoire of genes involved in K. oxytoca pathogenesis have been fully elucidated. Here, we showed that several animal isolates of K. oxytoca, including the clinical isolates, produced secreted products in bacterial culture supernatant that display cytotoxicity on HEp-2 and HeLa cells, indicating the ability to produce cytotoxin. Cytotoxin production appears to be regulated by the environment, and soy based product was found to have a strong toxin induction property. The toxin was identified, by liquid chromatography-mass spectrometry and NMR spectroscopy, as low molecular weight heat labile benzodiazepine, tilivalline, previously shown to cause cytotoxicity in several cell lines, including mouse L1210 leukemic cells. Genome sequencing and analyses of a cytotoxin positive K. oxytoca strain isolated from an abscess of a mouse, identified genes previously shown to promote pathogenesis in other enteric bacterial pathogens including ecotin, several genes encoding for type IV and type VI secretion systems, and proteins that show sequence similarity to known bacterial toxins including cholera toxin. To our knowledge, these results demonstrate for the first time, that animal isolates of K. oxytoca, produces a cytotoxin, and that cytotoxin production is under strict environmental regulation. We also confirmed tilivalline as the cytotoxin present in animal K. oxytoca strains. These findings, along with the discovery of a repertoire of genes with virulence potential, provide important insights into the pathogenesis of K. oxytoca. As a novel diagnostic tool, tilivalline may serve as a biomarker for K oxytoca-induced cytotoxicity in humans and animals through detection in various samples from food to diseased samples using LC-MS/MS. Induction of K. oxytoca cytotoxin by consumption of soy may be in part involved in the pathogenesis of gastrointestinal disease.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Toxinas Bacterianas / Benzodiazepinonas / Infecções por Klebsiella / Klebsiella oxytoca Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Toxinas Bacterianas / Benzodiazepinonas / Infecções por Klebsiella / Klebsiella oxytoca Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos
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