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Tetracycline-inactivating enzymes from environmental, human commensal, and pathogenic bacteria cause broad-spectrum tetracycline resistance.
Gasparrini, Andrew J; Markley, Jana L; Kumar, Hirdesh; Wang, Bin; Fang, Luting; Irum, Sidra; Symister, Chanez T; Wallace, Meghan; Burnham, Carey-Ann D; Andleeb, Saadia; Tolia, Niraj H; Wencewicz, Timothy A; Dantas, Gautam.
Afiliación
  • Gasparrini AJ; The Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Markley JL; Department of Chemistry, Washington University, St. Louis, MO, 63130, USA.
  • Kumar H; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Wang B; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Fang L; The Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Irum S; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Symister CT; Department of Chemistry, Washington University, St. Louis, MO, 63130, USA.
  • Wallace M; The Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Burnham CD; Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
  • Andleeb S; Department of Chemistry, Washington University, St. Louis, MO, 63130, USA.
  • Tolia NH; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Wencewicz TA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Dantas G; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Commun Biol ; 3(1): 241, 2020 05 15.
Article en En | MEDLINE | ID: mdl-32415166
Tetracycline resistance by antibiotic inactivation was first identified in commensal organisms but has since been reported in environmental and pathogenic microbes. Here, we identify and characterize an expanded pool of tet(X)-like genes in environmental and human commensal metagenomes via inactivation by antibiotic selection of metagenomic libraries. These genes formed two distinct clades according to habitat of origin, and resistance phenotypes were similarly correlated. Each gene isolated from the human gut encodes resistance to all tetracyclines tested, including eravacycline and omadacycline. We report a biochemical and structural characterization of one enzyme, Tet(X7). Further, we identify Tet(X7) in a clinical Pseudomonas aeruginosa isolate and demonstrate its contribution to tetracycline resistance. Lastly, we show anhydrotetracycline and semi-synthetic analogues inhibit Tet(X7) to prevent enzymatic tetracycline degradation and increase tetracycline efficacy against strains expressing tet(X7). This work improves our understanding of resistance by tetracycline-inactivation and provides the foundation for an inhibition-based strategy for countering resistance.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pseudomonas aeruginosa / Tetraciclinas / Resistencia a la Tetraciclina / Antibacterianos Límite: Humans Idioma: En Revista: Commun Biol Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pseudomonas aeruginosa / Tetraciclinas / Resistencia a la Tetraciclina / Antibacterianos Límite: Humans Idioma: En Revista: Commun Biol Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido