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Drugging evolution of antibiotic resistance at a regulatory network hub.
Zhai, Yin; Pribis, John P; Dooling, Sean W; Garcia-Villada, Libertad; Minnick, P J; Xia, Jun; Liu, Jingjing; Mei, Qian; Fitzgerald, Devon M; Herman, Christophe; Hastings, P J; Costa-Mattioli, Mauro; Rosenberg, Susan M.
Afiliación
  • Zhai Y; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
  • Pribis JP; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Dooling SW; Graduate Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, TX 77030, USA.
  • Garcia-Villada L; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Minnick PJ; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
  • Xia J; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Liu J; The Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Mei Q; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
  • Fitzgerald DM; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Herman C; The Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Hastings PJ; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Costa-Mattioli M; The Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Rosenberg SM; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Sci Adv ; 9(25): eadg0188, 2023 06 23.
Article en En | MEDLINE | ID: mdl-37352342
Evolution of antibiotic resistance is a world health crisis, fueled by new mutations. Drugs to slow mutagenesis could, as cotherapies, prolong the shelf-life of antibiotics, yet evolution-slowing drugs and drug targets have been underexplored and ineffective. Here, we used a network-based strategy to identify drugs that block hubs of fluoroquinolone antibiotic-induced mutagenesis. We identify a U.S. Food and Drug Administration- and European Medicines Agency-approved drug, dequalinium chloride (DEQ), that inhibits activation of the Escherichia coli general stress response, which promotes ciprofloxacin-induced (stress-induced) mutagenic DNA break repair. We uncover the step in the pathway inhibited: activation of the upstream "stringent" starvation stress response, and find that DEQ slows evolution without favoring proliferation of DEQ-resistant mutants. Furthermore, we demonstrate stress-induced mutagenesis during mouse infections and its inhibition by DEQ. Our work provides a proof-of-concept strategy for drugs to slow evolution in bacteria and generally.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Escherichia coli / Antibacterianos Límite: Animals Idioma: En Revista: Sci Adv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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: Escherichia coli / Antibacterianos Límite: Animals Idioma: En Revista: Sci Adv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos