Are Sphingolipids and Serine Dipeptide Lipids Underestimated Virulence Factors of Porphyromonas gingivalis?

Olsen, Ingar; Nichols, Frank C.

doi:10.1128/iai.00035-18

Cited by 30 publications

(28 citation statements)

References 52 publications

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“…Flavolipin (i.e., lipid 654) has been reported to signal to eukaryotic cells through an interaction with Toll-like receptor 2 (TLR2) (27,33). Diacylated lipid 654 has been shown to be converted into a more potent monoacylated derivative, lipid 430 (or lyso-lipid 654), through the action of phospholipase A2 activity in the host (21).…”

Section: Discussionmentioning

confidence: 99%

The Glycine Lipids of Bacteroides thetaiotaomicron Are Important for Fitness during Growth In Vivo and In Vitro

Lynch

Tammireddy

Doherty

et al. 2019

Appl Environ Microbiol

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Acylated amino acids function as important components of the cellular membrane in some bacteria. Biosynthesis is initiated by the N-acylation of the amino acid, and this is followed by subsequent O-acylation of the acylated molecule, resulting in the production of the mature diacylated amino acid lipid. In this study, we use both genetics and liquid chromatography-mass spectrometry (LC-MS) to characterize the biosynthesis and function of a diacylated glycine lipid (GL) species produced in Bacteroides thetaiotaomicron. We, and others, have previously reported the identification of a gene, named glsB in this study, that encodes an N-acyltransferase activity responsible for the production of a monoacylated glycine called N-acyl-3-hydroxy-palmitoyl glycine (or commendamide). In all of the Bacteroidales genomes sequenced so far, the glsB gene is located immediately downstream from a gene, named glsA, that is also predicted to encode a protein with acyltransferase activity. We use LC-MS to show that the coexpression of glsB and glsA results in the production of GL in Escherichia coli. We constructed a deletion mutant of the glsB gene in B. thetaiotaomicron, and we confirm that glsB is required for the production of GL in B. thetaiotaomicron. Moreover, we show that glsB is important for the ability of B. thetaiotaomicron to adapt to stress and colonize the mammalian gut. Therefore, this report describes the genetic requirements for the biosynthesis of GL, a diacylated amino acid species that contributes to fitness in the human gut bacterium B. thetaiotaomicron. IMPORTANCE The gut microbiome has an important role in both health and disease of the host. The mammalian gut microbiome is often dominated by bacteria from the Bacteroidales, an order that includes Bacteroides and Prevotella. In this study, we have identified an acylated amino acid, called glycine lipid, produced by Bacteroides thetaiotaomicron, a beneficial bacterium originally isolated from the human gut. In addition to identifying the genes required for the production of glycine lipids, we show that glycine lipids have an important role during the adaptation of B. thetaiotaomicron to a number of environmental stresses, including exposure to either bile or air. We also show that glycine lipids are important for the normal colonization of the murine gut by B. thetaiotaomicron. This work identifies glycine lipids as an important fitness determinant in B. thetaiotaomicron and therefore increases our understanding of the molecular mechanisms underpinning colonization of the mammalian gut by beneficial bacteria.

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Section: Discussionmentioning

confidence: 99%

The Glycine Lipids of Bacteroides thetaiotaomicron Are Important for Fitness during Growth In Vivo and In Vitro

Lynch

Tammireddy

Doherty

et al. 2019

Appl Environ Microbiol

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“…Flavolipin (i.e. Lipid 654) has been reported to signal to eukaryotic cells through an interaction with TLR2 (23, 33). The diacylated Lipid 654 has been shown to be converted into a more potent monoacylated derivative, Lipid 430 (or lyso-Lipid 654), through the action of phospholipase A2 activity in the host (17).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the role of glycine lipids inBacteroides thetaiotaomicron

Lynch

Tammireddy

Doherty

et al. 2018

Preprint

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18Acylated amino acids function as important components of the cellular membrane in some 19 bacteria. Biosynthesis is initiated by the N-acylation of the amino acid and this is followed by 20 subsequent O-acylation of the acylated molecule resulting in the production of the mature 21 diacylated amino acid lipid. In this study we use both genetics and liquid chromatography- 22 mass spectrometry (LC-MS) to characterize the biosynthesis and function of novel diacylated 23 glycine lipid (GL) species in Bacteroides thetaiotaomicron. We, and others, have previously 24 reported the identification of a gene, named glsB in this study, that encodes a N- 25 acyltransferase activity responsible for the production of a monoacylated glycine called N-26 acyl-3-hydroxy-palmitoyl glycine (or commendamide). In all of the Bacteroidales genomes so 27 far sequenced the glsB gene is located immediately downstream from a gene, named glsA, 28 also predicted to encode a protein with acyltransferase activity. We use LC-MS to show that 29 co-expression of glsB and glsA results in the production of GL in Escherichia coli. We 30 constructed a deletion mutant of the glsB gene in B. thetaiotaomicron and we confirm that 31 glsB is required for the production of GL in B. thetaiotaomicron. Moreover, we show that glsB 32 is important for the ability of B. thetaiotaomicron to adapt to stress and colonize the 33 mammalian gut. Therefore, this report is the first to describe the genetic requirements for 34 the biosynthesis of GL, a novel diacylated amino acids species that contributes to fitness in 35 the human gut bacterium, B. thetaiotaomicron. 36 37 38 39 42 healthy human gut microbiota (1). The gut-associated Bacteroidetes are required to digest 43 complex dietary glycans into short-chain fatty acids (such as acetate and propionate) that 44 are accessible to the host (2-4). A longitudinal study in infants has revealed the presence of 45 Bacteroides in the infant gut within 1 week of birth and some species of Bacteroides have 46 been shown to utilize the polysaccharides present in human breast milk (5, 6). Therefore it 47 has been suggested that Bacteroides may have an important role during the early 48 development of the infant gut (6). 49 50Acylated amino acids can be found in the membranes of many bacteria (7, 8). The best-51 characterized, and most widespread, acylated amino acid is ornithine lipid (OL). OL contains 52 a 3'-hydroxy fatty acid group attached by an amide linkage to the a-amino group of 53 ornithine with a second fatty acid group ester linked to the 3'-hydroxy group of the first 54 fatty acid (9). The genetics of OL production was first described in Sinorhizobium meliloti 55 where it was shown that a N-acyltransferase encoded by olsB catalysed the attachment of 56 the first fatty acid group to ornithine, resulting in monoacylated ornithine or lyso-OL (10). 57 The second fatty acid was subsequently attached to lyso-OL through the activity of an O-58 acyltransferase encoded by olsA, resulting in the producti...

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“…SL are found in the outer membrane (Godchaux & Leadbetter, ) and are required for gliding activity in Cytophaga species (Abbanat et al, ). Other unusual lipids found in Bacteroidetes include acylated amino acids and dipeptides and various ceramide derivatives (Farrokhi et al, ; Nemati et al, ; Olsen & Nichols, ; Rizza, Tucker, & White, ).…”

Section: Introductionmentioning

confidence: 99%

Fatty acid activation and utilization by Alistipes finegoldii, a representative Bacteroidetes resident of the human gut microbiome

Radka

Frank

Rock

et al. 2020

Molecular Microbiology

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Members of the Bacteroidetes phylum, represented by Alistipes finegoldii, are prominent anerobic, Gram‐negative inhabitants of the gut microbiome. The lipid biosynthetic pathways were analyzed using bioinformatic analyses, lipidomics, metabolic labeling and biochemistry to characterize exogenous fatty acid metabolism. A. finegoldii only produced the saturated fatty acids. The most abundant lipids were phosphatidylethanolamine (PE) and sulfonolipid (SL). Neither phosphatidylglycerol nor cardiolipin are present. PE synthesis is initiated by the PlsX/PlsY/PlsC pathway, whereas the SL pathway is related to sphingolipid biosynthesis. A. finegoldii incorporated medium‐chain fatty acids (≤14 carbons) into PE and SL after their elongation, whereas long‐chain fatty acids (≥16 carbons) were not elongated. Fatty acids >16 carbons were primarily incorporated into the 2‐position of phosphatidylethanolamine at the PlsC step, the only biosynthetic enzyme that utilizes long‐chain acyl‐ACP. The ability to assimilate a broad‐spectrum of fatty acid chain lengths present in the gut environment is due to the expression of two acyl‐acyl carrier protein (ACP) synthetases. Acyl‐ACP synthetase 1 had a substrate preference for medium‐chain fatty acids and synthetase 2 had a substrate preference for long‐chain fatty acids. This unique combination of synthetases allows A. finegoldii to utilize both the medium‐ and long‐chain fatty acid nutrients available in the gut environment to assemble its membrane lipids.

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Are Sphingolipids and Serine Dipeptide Lipids Underestimated Virulence Factors of Porphyromonas gingivalis?

Cited by 30 publications

References 52 publications

The Glycine Lipids of Bacteroides thetaiotaomicron Are Important for Fitness during Growth In Vivo and In Vitro

The Glycine Lipids of Bacteroides thetaiotaomicron Are Important for Fitness during Growth In Vivo and In Vitro

Characterization of the role of glycine lipids inBacteroides thetaiotaomicron

Fatty acid activation and utilization by Alistipes finegoldii, a representative Bacteroidetes resident of the human gut microbiome

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