Unsaturated long-chain free fatty acids are input signals of the Salmonella enterica PhoP/PhoQ regulatory system

VIARENGO, G.; SCIARA, M.I.; SALAZAR, M.; KIEFFER, P.; FURLAN, R. L.; GARCÍA VÉSCOVI, E.

JOURNAL OF BIOLOGICAL CHEMISTRY (ONLINE)

Cadmus

Año: 2013 p. 1 - 26

1083-351X

The Salmonella enterica serovar Typhimurium PhoP/PhoQ system has largely been studied as aparadigmatic 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 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 intra-cellular 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 independentlyof their cellular uptake and metabolic utilization by means of the β-oxidative pathway. Our finding puts forth the complexity of input signals that can converge to finely tune the activity of the PhoP/PhoQ system. Besides, it provides a new potential biochemical platform for the development of antibacterial strategies to fight against Salmonella infections.