Gut microbiota metabolism of l-carnitine and cardiovascular risk

Ussher, John R.; Lopaschuk, Gary D.; Arduini, Arduino

doi:10.1016/j.atherosclerosis.2013.10.013

Cited by 154 publications

(122 citation statements)

References 44 publications

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“…In contrast, a number of studies have demonstrated that L-carnitine has beneficial effects against disease conditions that include insulin resistance and ischemic heart disease. In addition, fish represent a significant source of TMAO, but consumption of fish and fish oils is associated with beneficial effects on cardiovascular health, [28] underlying the need for further studies to clarify this discrepancy.…”

Section: Nutrient Metabolism By the Intestinal Microbiotamentioning

confidence: 99%

Impact of the gut microbiota, prebiotics, and probiotics on human health and disease

Lin

Chang²,

et al. 2014

Biomed J

107

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Section: Nutrient Metabolism By the Intestinal Microbiotamentioning

confidence: 99%

Impact of the gut microbiota, prebiotics, and probiotics on human health and disease

Lin

Chang²,

et al. 2014

Biomed J

107

View full text Add to dashboard Cite

“…The development of novel analytical methods that use metagenomic sequencing for targeting gut microbiome enables us to identify the pathological roles of the microbiota in CAD 2) . For example, it has been postulated that the hepatic production of trimethylamine-N-oxide (TMAO) from gut microbiota-derived trimethylamine (TMA) could enhance CAD risk by promoting the development of atherosclerotic lesions both in humans and in animal models.…”

Section: See Article Vol 23: 908-921mentioning

confidence: 99%

Dysbiosis in the Pathophysiology of Coronary Artery Disease

Irie

Itoh

2016

JAT

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“…The TMA precursor is produced by gut microorganisms from carnitine, lecithin, or phosphatidylcholine contained in food (for example, red meat) and oxidized into TMAO in liver, and eventually, the oxidized molecule is transported via blood to the enteric site (39). Therefore, the activation of the Tor pathway by TMAO could occur when EHEC is in the animal gut.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Second Two-Component Signal Transduction System That Controls Fosfomycin Tolerance and Glycerol-3-Phosphate Uptake

et al. 2015

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Particular interest in fosfomycin has resurfaced because it is a highly beneficial antibiotic for the treatment of refractory infectious diseases caused by pathogens that are resistant to other commonly used antibiotics. The biological cost to cells of resistance to fosfomycin because of chromosomal mutation is high. We previously found that a bacterial two-component system, CpxAR, induces fosfomycin tolerance in enterohemorrhagic Escherichia coli (EHEC) O157:H7. This mechanism does not rely on irreversible genetic modification and allows EHEC to relieve the fitness burden that results from fosfomycin resistance in the absence of fosfomycin. Here we show that another two-component system, TorSRT, which was originally characterized as a regulatory system for anaerobic respiration utilizing trimethylamine-N-oxide (TMAO), also induces fosfomycin tolerance. Activation of the Tor regulatory pathway by overexpression of torR, which encodes the response regulator, or addition of TMAO increased fosfomycin tolerance in EHEC. We also show that phosphorylated TorR directly represses the expression of glpT, a gene that encodes a symporter of fosfomycin and glycerol-3-phosphate, and activation of the TorR protein results in the reduced uptake of fosfomycin by cells. However, cells in which the Tor pathway was activated had an impaired growth phenotype when cultured with glycerol-3-phosphate as a carbon substrate. These observations suggest that the TorSRT pathway is the second two-component system to reversibly control fosfomycin tolerance and glycerol-3-phosphate uptake in EHEC, and this may be beneficial for bacteria by alleviating the biological cost. We expect that this mechanism could be a potential target to enhance the utility of fosfomycin as chemotherapy against multidrug-resistant pathogens.A lthough fosfomycin is classified as an old antibiotic, it was recently revived as an antibiotic that could be effective against multidrug-resistant (MDR) pathogens, such as extended-spectrum-␤-lactamase (ESBL) producers (1). This antibiotic has no structural relationship to other commonly used antibiotics; therefore, it is not affected by the development of cross-resistance in MDR pathogens (2, 3). Fosfomycin is also used to decrease the risk of development of hemolytic-uremic syndrome (HUS), which is a fatal infectious disease caused by enterohemorrhagic Escherichia coli (EHEC) O157:H7 (4-6).Fosfomycin is an antagonist of phosphoenolpyruvate (PEP) and inhibits MurA activity, which transfers PEP to the 3=-hydroxyl group of UDP-N-acetylglucosamine in the initial step of bacterial cell wall biosynthesis (7). GlpT, which is a glycerol-3-phosphate transporter, and UhpT, which is a glucose-6-phosphate transporter, are involved in the uptake of fosfomycin (8-11). Mutations in the genes encoding these proteins that result in impaired fosfomycin binding or uptake confer resistance to fosfomycin. In some E. coli studies, mutations in genes encoding the positive regulators of uhpT expression, UhpA and CyaA, confer resistance because the...

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Gut microbiota metabolism of l-carnitine and cardiovascular risk

Cited by 154 publications

References 44 publications

Impact of the gut microbiota, prebiotics, and probiotics on human health and disease

Impact of the gut microbiota, prebiotics, and probiotics on human health and disease

Dysbiosis in the Pathophysiology of Coronary Artery Disease

Identification of a Second Two-Component Signal Transduction System That Controls Fosfomycin Tolerance and Glycerol-3-Phosphate Uptake

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