title: Unsaturated long chain free fatty acids are input signals of the Salmonella enterica PhoP/PhoQ regulatory system.
abstract: The Salmonella enterica serovar Typhimurium PhoP/PhoQ system has largely been studied as a paradigmatic two-component regulatory system not only to dissect structural and functional aspects of signal transduction in bacteria but also to gain knowledge about the versatile devices that have evolved allowing a pathogenic bacterium to adjust to or counteract environmental stressful conditions along its life cycle. Mg(2+) limitation, acidic pH, and the presence of cationic antimicrobial peptides have been identified as cues that the sensor protein PhoQ can monitor to reprogram Salmonella gene expression to cope with extra- or intracellular challenging conditions. In this work, we show for the first time that long chain unsaturated free fatty acids (LCUFAs) present in Salmonella growth medium are signals specifically detected by PhoQ. We demonstrate that LCUFAs inhibit PhoQ autokinase activity, turning off the expression of the PhoP-dependent regulon. We also show that LCUFAs exert their action independently of their cellular uptake and metabolic utilization by means of the β-oxidative pathway. Our findings put forth the complexity of input signals that can converge to finely tune the activity of the PhoP/PhoQ system. In addition, they provide a new potential biochemical platform for the development of antibacterial strategies to fight against Salmonella infections.
authors.affiliation: Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET), Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Predio CCT-CONICET-Rosario, Ocampo y Esmeralda, 2000 Rosario, Argentina.
authors.forename: Gastón
authors.initials: G
authors.lastname: Viarengo
authors.forename: Mariela I
authors.initials: MI
authors.lastname: Sciara
authors.forename: Mario O
authors.initials: MO
authors.lastname: Salazar
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Kieffer
authors.forename: Ricardo L E
authors.initials: RL
authors.lastname: Furlán
authors.forename: Eleonora
authors.initials: E
authors.lastname: García Véscovi
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D013058:Mass Spectrometry; D019906:Nuclear Magnetic Resonance, Biomolecular; D060888:Real-Time Polymerase Chain Reaction; D019779:Salmonella enterica / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D005231:Fatty Acids, Unsaturated; C079792:PhoQ protein, Bacteria; C061278:PhoB protein, Bacteria
keywords: Bacterial Pathogenesis; Bacterial Protein Kinases; Bacterial Signal Transduction; Bacterial Transcription; Histidine Kinases; PhoP/PhoQ Input Signal; Salmonella; Two-component System; Unsaturated Fatty Acids