Compartment and signal-specific codependence in the transcriptional control of Salmonella periplasmic copper homeostasis.
Copper homeostasis is essential for bacterial pathogen fitness and infection, and has been the focus of a number of recent studies. In Salmonella, envelope protection against copper overload and macrophage survival depends on CueP, a major copper-binding protein in the periplasm. This protein is also required to deliver the metal ion to the Cu/Zn superoxide dismutase SodCII. The Salmonella-specific CueP-coding gene was originally identified as part of the Cue regulon under the transcriptional control of the cytoplasmic copper sensor CueR, but its expression differs from the rest of CueR-regulated genes. Here we show that cueP expression is controlled by the concerted action of CueR, which detects the presence of copper in the cytoplasm, and by CpxR/CpxA, which monitors envelope stress. Copper-activated CueR is necessary for the appropriate spatial arrangement of the -10 and -35 elements of the cueP promoter, and CpxR is essential to recruit the RNA polymerase. The integration of two ancestral sensory systems-CueR, which provides signal specificity, and CpxR/CpxA, which detects stress in the bacterial envelope-restricts the expression of this periplasmic copper resistance protein solely to cells encountering surplus copper that disturbs envelope homeostasis, emulating the role of the CusR/CusS regulatory system present in other enteric bacteria.
Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Instituto de Biología Molecular y Celular de Rosario, Universidad Nacional de Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas, 2000-Rosario, Argentina.
Alejandro
A
Pezza
Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Instituto de Biología Molecular y Celular de Rosario, Universidad Nacional de Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas, 2000-Rosario, Argentina.
Lucas B
LB
Pontel
Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Instituto de Biología Molecular y Celular de Rosario, Universidad Nacional de Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas, 2000-Rosario, Argentina.
Carolina
C
López
Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Instituto de Biología Molecular y Celular de Rosario, Universidad Nacional de Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas, 2000-Rosario, Argentina soncini@ibr-conicet.gov.ar.
Fernando C
FC
Soncini
D001426:Bacterial Proteins / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D003300:Copper / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D009875:Operator Regions, Genetic / Q000235:genetics; D019897:Periplasm / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010802:Phylogeny; D011190:Potassium Cyanide / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D018085:Regulon / Q000235:genetics; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
D001426:Bacterial Proteins; D003300:Copper; D012321:DNA-Directed RNA Polymerases; D011190:Potassium Cyanide
CpxR/CpxA; CueP; Salmonella; periplasmic copper homeostasis; transcriptional codependence
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