Discovery and quantification of lipoamino acids in bacteria

Hueber, Amandine; Petitfils, Camille; Faouder, Pauline Le; Langevin, Geoffrey; Guy, Alexandre; Galano, Jean‐Marie; Martin, Jean-François; Tabet, Jean‐Claude; Cenac, Nicolas; Bertrand‐Michel, Justine

doi:10.1016/j.aca.2021.339316

Cited by 6 publications

(13 citation statements)

References 36 publications

(41 reference statements)

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“…As the abundance of L. murinus IRSD_2020 was inversely correlated to the visceral sensitivity, we hypothesised that these bacteria produced a metabolite decreasing visceral sensitivity. Based on our previous study where we described the production of an analgesic GABA-containing lipopeptide by E. coli strain14 14 and on our studies identifying several lipoamines in bacteria,15 16 we developed a method to quantify the concentration of lipopeptides containing GABA: C12AlaGABA, C12AsnGABA, C14AsnGABA, C14:1AlaGABA, C12ValGABA, C12LeuGABA, C14GABA, C12IleGABA, C14IleGABA, C16LeuGABA, C16PheGABA and C16GluGABA (online supplemental methods). In L. murinus IRSD_2020, as no clear production of lipopeptides-GABA was observed (online supplemental figure 6A and table S5) and as these bacteria did not express the enzymes implicated in GABA synthesis, we cultured L. murinus IRSD_2020 in the presence of GABA.…”

Section: Resultsmentioning

confidence: 99%

“…In a previous study, we highlighted that a probiotic, Escherichia coli Nissle 1917, produces a lipopeptide, the C12-asparagine-γ-aminobutyric acid (C12AsnGABA) that decreases both neuronal activation induced by pro-nociceptive molecules in vitro and capsaicin-induced hypersensitivity in vivo 14. We then determined lipoamino acid (LpAA) and GABA–lipopeptide structures by high-resolution mass spectrometry and developed a quantitative method of newly identified LpAA and lipopeptide–GABA by liquid chromatography coupled to mass spectrometry (LC-MS/MS) in different strains of bacteria 15 16…”

Section: Introductionmentioning

confidence: 99%

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Identification of bacterial lipopeptides as key players in IBS

Petitfils

Maurel

Payros

et al. 2022

Gut

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ObjectivesClinical studies revealed that early-life adverse events contribute to the development of IBS in adulthood. The aim of our study was to investigate the relationship between prenatal stress (PS), gut microbiota and visceral hypersensitivity with a focus on bacterial lipopeptides containing γ-aminobutyric acid (GABA).DesignWe developed a model of PS in mice and evaluated, in adult offspring, visceral hypersensitivity to colorectal distension (CRD), colon inflammation, barrier function and gut microbiota taxonomy. We quantified the production of lipopeptides containing GABA by mass spectrometry in a specific strain of bacteria decreased in PS, in PS mouse colons, and in faeces of patients with IBS and healthy volunteers (HVs). Finally, we assessed their effect on PS-induced visceral hypersensitivity.ResultsPrenatally stressed mice of both sexes presented visceral hypersensitivity, no overt colon inflammation or barrier dysfunction but a gut microbiota dysbiosis. The dysbiosis was distinguished by a decreased abundance ofLigilactobacillus murinus, in both sexes, inversely correlated with visceral hypersensitivity to CRD in mice. An isolate from this bacterial species produced several lipopeptides containing GABA including C14AsnGABA. Interestingly, intracolonic treatment with C14AsnGABA decreased the visceral sensitivity of PS mice to CRD. The concentration of C16LeuGABA, a lipopeptide which inhibited sensory neurons activation, was decreased in faeces of patients with IBS compared with HVs.ConclusionPS impacts the gut microbiota composition and metabolic function in adulthood. The reduced capacity of the gut microbiota to produce GABA lipopeptides could be one of the mechanisms linking PS and visceral hypersensitivity in adulthood.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of bacterial lipopeptides as key players in IBS

Petitfils

Maurel

Payros

et al. 2022

Gut

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“…Recently, CID from nonresonant activation of [C16Glu-H] − ( m / z 384) using Qq/TOF MS was shown to unexpectedly yield the fatty acid [(C16Glu-H)-(Glu-H 2 O)] − ( m / z 255) carboxylate regeneration and its complementary [(Glu-H)-H 2 O] − dehydrated glutamate ( m / z 128). Regeneration of the fatty acid carboxylate was unexpected since, under same collisional conditions, it did not occur from [ Lp AA-H] − consisting of a basic or nonpolar chain . The exclusive formation of such a long chain carboxylate from [ Lp Glu-H] − ( Lp as the C12 and C16 acyl conjugates) particularly attracted our attention in this study, since its breakdown profile, constituting the ERMS of [ Lp Glu-H] − appears as a broadened monomodal curve (compared to the other product ion profiles).…”

Section: Introductionmentioning

confidence: 91%

Energy-Resolved Ion Mobility Spectrometry: Composite Breakdown Curves for Distinguishing Isomeric Product Ions

Hueber

Green

Ujma

et al. 2022

J. Am. Soc. Mass Spectrom.

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Identification of lipopeptides (LpAA) synthesized from bacteria involves the study of structural characterization. Twenty LpAA have been characterized using commercial tandem high-resolution mass spectrometers in negative electrospray, employing nonresonant excitation in "RF only" collision cells and generally behave identically. However, [LpAA-H] − (AA = Asp or Glu) shows surprising fragmentation pathways, yielding a complementary fatty acid carboxylate and dehydrated amino acid fragment anions. In this study, the dissociation mechanisms of [C12Glu-H] − were determinate using energy-resolved mass spectrometry (ERMS). Product ion breakdown profiles are, generally, unimodal with full width at half-maximum (fwhm) increasing as product ion m/z ratios decrease, except for the two product ions of interest (fatty acid carboxylate and dehydrated glutamate) characterized by broad and composite profiles. Such behavior was already shown for other ions using a custom-built guided ion beam mass spectrometer. In this study, we investigate the meaning of these particular profiles from an ERMS breakdown, using fragmentation mechanisms depending on the collision energy. ERMS on line with ion mobility spectrometry (IMS), here called ER-IMS, provides a way to probe such questions. Broad or composite profiles imply that the corresponding product ions may be generated by two (or more) pathways, resulting in common or isomeric product ion structures. ER-IMS analysis indicates that the fatty acid carboxylate product ion is produced with a common structure through different pathways, while dehydrated glutamate has two isomeric forms depending on the mechanism involved. Drift time values correlate with the calculated collision cross section that confirms the product ion structures and fragmentation mechanisms.

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“…Overall the SPPS strategy allowed to access in minimum time and high purity to a large set of new lipopeptides necessary for the discovery and quantification of lipoamino acids in bacteria [76] …”

Section: Lipopeptidesmentioning

confidence: 99%

“…[73] necessary for the discovery and quantification of lipoamino acids in bacteria. [76] 7. Cysteinyl-SPM Specialized proresolving mediators (SPM) are oxylipins that are actively involved in the clearance and regulation of inflammatory exudates to allow the restoration of tissue homeostasis.…”

Section: Lipopeptidesmentioning

confidence: 99%