title: CysB-dependent upregulation of the Salmonella Typhimurium cysJIH operon in response to antimicrobial compounds that induce oxidative stress.
abstract: It has been proposed that some antibiotics exert additional damage through reactive oxygen species (ROS) production. Since H₂S protects neurons and cardiac muscle from oxidative stress, it has been hypothesized that bacterial H₂S might, similarly, be a cellular protector against antibiotics. In Enterobacteriaceae, H₂S can be produced by the cysJIH pathway, which uses sulfate as the sulfur source. CysB, in turn, is a positive regulator of cysJIH. At present, the role of S. Typhimurium cysJIH operon in the protection to reactive oxygen species (ROS) induced by antimicrobial compounds remains to be elucidated. In this work, we evaluated the role of cysJIH and cysB in ROS accumulation, superoxide dismutase (SOD) activity, reduced thiol accumulation, and H₂S accumulation in S. Typhimurium, cultured in either sulfate or cysteine as the sole sulfur source. Furthermore, we assessed the effects of the addition of ceftriaxone (CEF) and menadione (MEN) in these same parameters. In sulfate as the sole sulfur source, we found that the cysJIH operon and the cysB gene were required to full growth in minimal media, independently on the addition of CEF or MEN. Most importantly, both cysJIH and cysB contributed to diminish ROS levels, increase the SOD activity, increase the reduced thiols, and increase the H₂S levels in presence of CEF or MEN. Moreover, the cysJIH operon exhibited a CysB-dependent upregulation in presence of these two antimicrobials compounds. On the other hand, when cysteine was used as the sole sulfur source, we found that cysJIH operon was completely negligible, were only cysB exhibited similar phenotypes than the described for sulfate as sulfur source. Unexpectedly, CysB downregulated cysJIH operon when cysteine was used instead of sulfate, suggesting a complex regulation of this system.
authors: Laboratorio de Genética y Patogénesis Bacteriana, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
authors: Ricardo
authors: R
authors: Álvarez
authors: Laboratorio de Genética y Patogénesis Bacteriana, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
authors: German
authors: G
authors: Neumann
authors: Laboratorio de Genética y Patogénesis Bacteriana, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
authors: Jorge
authors: J
authors: Frávega
authors: Laboratorio de Genética y Patogénesis Bacteriana, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
authors: Fernando
authors: F
authors: Díaz
authors: Laboratorio de Genética y Patogénesis Bacteriana, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
authors: Cristóbal
authors: C
authors: Tejías
authors: Bionanotechnology and Microbiology Lab, Center for Bioinformatics and Integrative Biology, Universidad Andres Bello, Santiago, Chile.
authors: Bernardo
authors: B
authors: Collao
authors: Laboratorio de Microbiología, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
authors: Juan A
authors: JA
authors: Fuentes
authors: Gut Microbiota and Clostridia Research Group, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
authors: Daniel
authors: D
authors: Paredes-Sabja
authors: Laboratorio de Genética y Patogénesis Bacteriana, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
authors: Iván L
authors: IL
authors: Calderón
authors: Laboratorio de Genética y Patogénesis Bacteriana, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile. Electronic address: fernandogil@unab.cl.
authors: Fernando
authors: F
authors: Gil
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002443:Ceftriaxone / Q000494:pharmacology; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006862:Hydrogen Sulfide / Q000378:metabolism; D008969:Molecular Sequence Data; D009876:Operon / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism; D050864:Sulfite Reductase (NADPH) / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D024483:Vitamin K 3 / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003470:Culture Media; C489265:CysB protein, Salmonella typhimurium; D017382:Reactive Oxygen Species; D013431:Sulfates; D024483:Vitamin K 3; D002443:Ceftriaxone; D013482:Superoxide Dismutase; D050864:Sulfite Reductase (NADPH); D006862:Hydrogen Sulfide
keywords: Ceftriaxone resistance; H(2)S production; Oxidative stress; cysJIH