Free fatty acid concentrations in gallbladder bile collected from Chilean patients with gallstones

Tsuchiya, Yasuo; Serra, I; Hori, Yasushi; Calvo, Alfonso; Villegas, Rodrigo; Shibuya, Norio; Nakamura, Kazutoshi; Yamamoto, Masahiro

doi:10.1016/j.clinbiochem.2005.11.006

Cited by 2 publications

(3 citation statements)

References 10 publications

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“…We have shown that fresh bile also represses the PhoP-regulated genes by the inhibition of PhoQ autokinase activity, similarly to purified LA or CLA. In bile from patients with cholelithiasis, Tsuchiya et al (43) reported concentrations of individual free LCUFAs in the range of 0.23 to 2.0 mM, which is in agreement with the concentrations that inhibited PhoP/PhoQ activity in this study.…”

Section: Discussionsupporting

confidence: 91%

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PhoQ is an unsaturated fatty acid receptor that fine-tunes Salmonella pathogenic traits

et al. 2020

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The Salmonella enterica PhoP/PhoQ two-component signaling system coordinates the spatiotemporal expression of key virulence factors that confer pathogenic traits. Through biochemical and structural analyses, we found that the sensor histidine kinase PhoQ acted as a receptor for long-chain unsaturated fatty acids (LCUFAs), which induced a conformational change in the periplasmic domain of the PhoQ protein. This resulted in the repression of PhoQ autokinase activity, leading to inhibition of the expression of PhoP/PhoQ-dependent genes. Recognition of the LCUFA linoleic acid (LA) by PhoQ was not stereospecific because positional and geometrical isomers of LA equally inhibited PhoQ autophosphorylation, which was conserved in multiple S. enterica serovars. Because orally acquired Salmonella encounters conjugated LA (CLA), a product of the metabolic conversion of LA by microbiota, in the human intestine, we tested how short-term oral administration of CLA affected gut colonization and systemic dissemination in a mouse model of Salmonella-induced colitis. Compared to untreated mice, CLA-treated mice showed increased gut colonization by wild-type Salmonella, as well as increased dissemination to the spleen. In contrast, the inability of the phoP strain to disseminate systemically remained unchanged by CLA treatment. Together, our results reveal that, by inhibiting PhoQ, environmental LCUFAs fine-tune the fate of Salmonella during infection. These findings may aid in the design of new anti-Salmonella therapies.

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Section: Discussionsupporting

confidence: 91%

“…The potential inhibitory effect of fatty acids was evaluated by growing Salmonella Typhimurium wild-type strain in LB in sterile 96-well microtiter plates, as described in (13,43). Fatty acids were tested in serial twofold dilutions from 0 to 2 mg•ml −1 .…”

Section: Effect Of Lcufas On Salmonella Growthmentioning

confidence: 99%

PhoQ is an unsaturated fatty acid receptor that fine-tunes Salmonella pathogenic traits

et al. 2020

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“…Chaterjee et al (56) reported that linoleic acid represents 14%, whereas oleic acid represents 23%, of total fatty acids present in ox bile. In bile of cholelithiasis patients, Tsuchiya et al (67) reported concentrations of individual free LCUFAs in the 0.23-2.0 mM range, which is in agreement with PhoP/PhoQ activity inhibitory values shown in this work.…”

Section: Discussionsupporting

confidence: 78%

Unsaturated Long Chain Free Fatty Acids Are Input Signals of the Salmonella enterica PhoP/PhoQ Regulatory System

Viarengo

Sciara

Salazar

et al. 2013

Journal of Biological Chemistry

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Free fatty acid concentrations in gallbladder bile collected from Chilean patients with gallstones

Cited by 2 publications

References 10 publications

PhoQ is an unsaturated fatty acid receptor that fine-tunes Salmonella pathogenic traits

PhoQ is an unsaturated fatty acid receptor that fine-tunes Salmonella pathogenic traits

Unsaturated Long Chain Free Fatty Acids Are Input Signals of the Salmonella enterica PhoP/PhoQ Regulatory System

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