Editors' ChoiceMicrobiology

Fatty Acids as Environmental Cues?

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Science Signaling  13 Aug 2013:
Vol. 6, Issue 288, pp. ec189
DOI: 10.1126/scisignal.2004601

Virulence of the intracellular pathogen Salmonella typhimurium is controlled by the two-component PhoP/PhoQ system. The sensor in this system is the transmembrane protein PhoQ, which has histidine kinase or phosphatase activity, depending on environmental factors such as pH and Mg2+ availability. The cytoplasmic response regulator and target of PhoQ enzymatic activity in this system is PhoP, a transcription factor that is active in its phosphorylated form and promotes expression of genes required for survival inside host cells. Viarengo et al. report that the PhoP/PhoQ system is also responsive to long-chain unsaturated free fatty acids (LCUFAs). When Mg2+ is limiting, PhoQ phosphorylates PhoP to stimulate the expression of PhoP-responsive target genes; the presence of Mg2+ promotes PhoQ phosphatase activity, leading to repression of PhoP targets. When added to Salmonella growth medium, plant-derived mixed LCUFAs and various purified LCUFAs repressed expression of PhoP-activated reporter genes, to a similar extent to that caused by the addition of MgCl2. Addition of various purified LCUFAs to Salmonella cultures dose-dependently inhibited the in vitro autokinase activity of PhoQ isolated from these cells. These effects did not require metabolism or biochemical modification of the LCUFAs and were not observed when cultures were treated with the corresponding long-chain saturated fatty acids. Sequence and predictive structural analyses did not identify an apparent free fatty acid–binding domain in PhoQ, so the mechanism by which PhoQ activity is modulated by LCUFAs remains unknown. These findings demonstrate the versatility of PhoQ in responding to environmental cues and suggest a model for how Salmonella distinguishes between intracellular and extracellular environments. The authors hypothesize that LCUFAs in bile and digested food in the intestine may repress the Salmonella virulence program until the bacteria have successfully entered vacuoles in the host cell, where additional cues such as acidic pH activate the PhoP/PhoQ system to promote the expression of the virulence factors that enable survival and replication.

G. Viarengo, M. I. Sciara, M. O. Salazar, P. M. Kieffer, R. L. E. Furlán, E. García Véscovi, Unsaturated long chain free fatty acids are input signals of the Salmonella enterica PhoP/PhoQ regulatory system. J. Biol. Chem. 288, 22346–22358 (2013). [Abstract] [Full Text]

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