Glycine and its N-methylated analogues cause pH-dependent membrane damage to enterotoxigenic Escherichia coli

Vanhauteghem, Donna; Janssens, Geert; Lauwaerts, Angelo; Sys, Stanislas U.; Boyen, Filip; Kalmar, Isabelle; Meyer, Evelyne

doi:10.1007/s00726-011-1068-y

Cited by 12 publications

(19 citation statements)

References 42 publications

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“…Cools et al (2010) found an improvement of crude fat, CP, and nitrogen-free extract apparent digestibility when 500 mg of DMG-Na/ kg of feed was supplemented in sow diets. This beneficial effect confirms the hypothesis that DMG acts as an emulsifying agent, as recently proven by Vanhauteghem et al (2012).…”

Section: Introductionsupporting

confidence: 76%

Effects of N,N-dimethylglycine sodium salt on apparent digestibility, vitamin E absorption, and serum proteins in broiler chickens fed a high- or low-fat diet

Prola

Nery

Lauwaerts³

et al. 2013

Poultry Science

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The objective of this study was to assess the effect of supplementation with sodium salt of N,Ndimethylglycine (DMG-Na) on apparent digestibility (AD) in broiler chickens fed low-and high-fat diets. Twenty-eight 1-d-old broiler chickens were fed one of the dietary treatments: a low-fat diet (LF) or a high-fat diet (HF) supplemented with or without 1,000 mg/kg of DMG-Na. Body weight and feed consumption were recorded at 14 and 35 d of age. Average daily growth, daily feed intake, and feed conversion ratio were calculated. The AD of DM, organic matter (OM), CP, total fat (TF), and α-tocopheryl-acetate were assessed by 2 digestibility trials (at 18-21 and 32-35 d, respectively). Serum protein and plasma α-tocopherol concentrations were assessed at 35 d of age. Final BW, feed intake, carcass, breast, and spleen weight were higher in groups fed LF than HF diets (P = 0.048, P = 0.002, P = 0.039, P < 0.001, P = 0.007, respectively). Liver weight was increased in DMG-Na-unsupplemented groups (P = 0.011) for both fat levels. During the first digestibility trial (18-21 d), the AD of DM (P = 0.023), OM (P = 0.033), CP (P = 0.030), and α-tocopheryl-acetate (P = 0.036) was higher in the DMG-Na-supplemented group than control. Digestibility of total fat was increased by DMG-Na supplementation in the LF groups (P = 0.038). A trend for improvement of digestibility was observed during the second digestibility trial (32-35 d) for DM (P = 0.089), OM (P = 0.051), and CP (P = 0.063) in DMG-Na groups. Total serum proteins (and relative fractions) were positively influenced by DMGNa supplementation both in LF and HF diets (P = 0.029). Plasma α-tocopherol concentration was higher in groups fed LF than HF diets (P < 0.001).

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Section: Introductionsupporting

confidence: 76%

Effects of N,N-dimethylglycine sodium salt on apparent digestibility, vitamin E absorption, and serum proteins in broiler chickens fed a high- or low-fat diet

Prola

Nery

Lauwaerts³

et al. 2013

Poultry Science

Self Cite

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“…As previously shown for stationary phase ETEC [1], flow cytometric analysis of membrane integrity of log phase ETEC with SYTO 9/PI dual staining revealed a unique fluorescence pattern, directly related to the degree of membrane damage. Three bacterial subpopulations could thus be identified: membrane-intact live bacteria (A), membrane-damaged “intermediates” (B) and dead bacteria (C).…”

Section: Resultssupporting

confidence: 75%

“…All compounds were stored to manufacturers' guidelines until use. Compound characteristics are described by Vanhauteghem et al [1].…”

Section: Methodsmentioning

confidence: 99%

“…We recently described a decrease in the viability of stationary phase enterotoxigenic Escherichia coli ( E. coli, ETEC ) associated with membrane damage and reduced growth capacity caused by glycine and its N -methylated derivatives N -methylglycine (sarcosine), N,N -dimethylglycine (DMG) under alkaline stress conditions [1]. In contrast, the trimethylated analogue of glycine, betaine, did not affect bacterial viability.…”

Section: Introductionmentioning

confidence: 99%

“…In our previous work we established the loss of membrane integrity due to exposure to glycine, sarcosine and DMG under alkaline conditions [1]. These experiments were repeated using log phase E. coli and the occurrence of membrane damage was further assessed by measuring the leakage of nucleic [18].…”

Section: Introductionmentioning

confidence: 99%

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Exposure to the Proton Scavenger Glycine under Alkaline Conditions Induces Escherichia coli Viability Loss

Vanhauteghem

Janssens

Lauwaerts³

et al. 2013

PLoS ONE

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Our previous work described a clear loss of Escherichia coli (E. coli) membrane integrity after incubation with glycine or its N-methylated derivatives N-methylglycine (sarcosine) and N,N-dimethylglycine (DMG), but not N,N,N-trimethylglycine (betaine), under alkaline stress conditions. The current study offers a thorough viability analysis, based on a combination of real-time physiological techniques, of E. coli exposed to glycine and its N-methylated derivatives at alkaline pH. Flow cytometry was applied to assess various physiological parameters such as membrane permeability, esterase activity, respiratory activity and membrane potential. ATP and inorganic phosphate concentrations were also determined. Membrane damage was confirmed through the measurement of nucleic acid leakage. Results further showed no loss of esterase or respiratory activity, while an instant and significant decrease in the ATP concentration occurred upon exposure to either glycine, sarcosine or DMG, but not betaine. There was a clear membrane hyperpolarization as well as a significant increase in cellular inorganic phosphate concentration. Based on these results, we suggest that the inability to sustain an adequate level of ATP combined with a decrease in membrane functionality leads to the loss of bacterial viability when exposed to the proton scavengers glycine, sarcosine and DMG at alkaline pH.

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Metabolites related to renal function, immune activation, and carbamylation are associated with muscle composition in older adults

Lustgarten

Fielding

2017

Experimental Gerontology

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Reduced skeletal muscle density in older adults is associated with insulin resistance, decreased physical function, and an increased all-cause mortality risk. To elucidate mechanisms that may underlie the maintenance of skeletal muscle density, we conducted a secondary analysis of previously published muscle composition and serum metabolomic data in 73 older adults (average age, 78y). Multivariable-adjusted linear regression was used to examine associations between 321 metabolites with muscle composition, defined as the ratio between normal density (NDM) with low density (LDM) thigh muscle cross sectional area (NDM/LDM). Sixty metabolites were significantly (p≤0.05 and q<0.30) associated with NDM/LDM. Decreased renal function and the immune response have been previously linked with reduced muscle density, but the mechanisms underlying these connections are less clear. Metabolites that were significantly associated with muscle composition were then tested for their association with circulating markers of renal function (blood urea nitrogen, creatinine, uric acid), and with the immune response (neutrophils/lymphocytes) and activation (kynurenine/tryptophan). 43 significant NDM/LDM metabolites (including urea) were co-associated with at least 1 marker of renal function; 23 of these metabolites have been previously identified as uremic solutes. The neutrophil/lymphocyte ratio was significantly associated with NDM/LDM (β±SE: -0.3±0.1, p=0.01, q=0.04). 35 significant NDM/LDM metabolites were co-associated with immune activation. Carbamylation (defined as homocitrulline/lysine) was identified as a pathway that may link renal function and immune activation with muscle composition, as 29 significant NDM/LDM metabolites were co-associated with homocitrulline/lysine, with at least 2 markers of renal function, and with kynurenine/tryptophan. When considering that elevated urea and uremic metabolites have been linked with an increased systemic microbial burden, that antimicrobial defense can be reduced in the presence of carbamylation, and that adipocytes can promote host defense, we propose the novel hypothesis that the age-related increase in adipogenesis within muscle may be a compensatory antimicrobial response to protect against an elevated microbial burden.

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Glycine and its N-methylated analogues cause pH-dependent membrane damage to enterotoxigenic Escherichia coli

Cited by 12 publications

References 42 publications

Effects of N,N-dimethylglycine sodium salt on apparent digestibility, vitamin E absorption, and serum proteins in broiler chickens fed a high- or low-fat diet

Effects of N,N-dimethylglycine sodium salt on apparent digestibility, vitamin E absorption, and serum proteins in broiler chickens fed a high- or low-fat diet

Exposure to the Proton Scavenger Glycine under Alkaline Conditions Induces Escherichia coli Viability Loss

Metabolites related to renal function, immune activation, and carbamylation are associated with muscle composition in older adults

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