Dataset Information

Investigating the mechanism(s) underlying tryptamine and phenethylamine inhibition on insulin signaling

ABSTRACT: To investigate the mechanism(s) underlying tryptamine inhibition on insulin signaling, we employed a phospho-proteomics approach to capture the molecular components that are significantly altered by tryptamine.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Fat Body

DISEASE(S): Disease Free

SUBMITTER: Lixiang Zhai

LAB HEAD: Lixiang Zhai

PROVIDER: PXD044161 | Pride | 2023-10-24

REPOSITORIES: Pride

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Publications

Gut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome.

Zhai Lixiang L Xiao Haitao H Lin Chengyuan C Wong Hoi Leong Xavier HLX Lam Yan Y YY Gong Mengxue M Wu Guojun G Ning Ziwan Z Huang Chunhua C Zhang Yijing Y Yang Chao C Luo Jingyuan J Zhang Lu L Zhao Ling L Zhang Chenhong C Lau Johnson Yiu-Nam JY Lu Aiping A Lau Lok-Ting LT Jia Wei W Zhao Liping L Bian Zhao-Xiang ZX

Nature communications 20230817 1

The incidence of metabolic syndrome is significantly higher in patients with irritable bowel syndrome (IBS), but the mechanisms involved remain unclear. Gut microbiota is causatively linked with the development of both metabolic dysfunctions and gastrointestinal disorders, thus gut dysbiosis in IBS may contribute to the development of metabolic syndrome. Here, we show that human gut bacterium Ruminococcus gnavus-derived tryptamine and phenethylamine play a pathogenic role in gut dysbiosis-induce ...[more]

PMID: 37591886

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Project description:Pyruvate oxidase encoded by spxB is a major virulence factor in the human respiratory pathogen Streptococcus pneumoniae. During aerobic growth, SpxB synthesizes large amounts of H2O2 and acetyl phosphate, which can serve as a phosphoryl group donor to response regulators and be converted to ATP. SpxB is the main source of the millimolar concentrations of H2O2 produced and tolerated by pneumococcus, despite its lack of a catalase. We report here the first cis- and trans-acting regulatory elements for spxB transcription. These elements were identified in a genetic screen, similar to those used previously for phase variants, for spontaneous mutations that caused colonies of virulent serotype 2 strain D39 to change from a transparent to an opaque appearance. Six of the seven opaque colonies recovered (frequency of 3 x 10-5) were impaired for SpxB function. Modeling suggested that two mutations changed amino acids in SpxB required for FAD cofactor or subunit binding. One mutation deleted a cis-acting adjacent direct repeat required for optimal spxB transcription. The other three independent mutations created the same frameshift near the start of a trans-acting regulatory gene designated as spxR. The SpxR protein contains helix-turn-helix, CBS, and HotDog domains implicated in DNA, adenosine, and CoA compound binding, respectively, consistent with the idea that SpxR positively regulates spxB transcript amount in response to energy and metabolic state rather than oxidative state. Finally, microarray analyses of a null spxB or a spxR mutant revealed the presence of a new oxidative stress response in pneumococcus and unexpectedly demonstrated that SpxR strongly positively regulates the transcript amount of the strH exoglycosidase gene, which like spxB, has been implicated in host colonization. Keywords: genetic modification Bacterial strains were grown exponentially in rich (BHI) media at 37C and an atmosphere of 5% CO2, and were processed as described in the related Sample records. Samples were collected from three independent biological replicates and included one dye swap. Data were normalized using the Lowess (subgrid) method without background subtraction.

Dataset Information

Investigating the mechanism(s) underlying tryptamine and phenethylamine inhibition on insulin signaling

Publications

Gut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome.

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