Deciphering the tRNA-dependent lipid aminoacylation systems in bacteria: Novel components and structural advances

Fields, Rachel N.; Roy, Hervé

doi:10.1080/15476286.2017.1356980

Cited by 24 publications

(40 citation statements)

References 117 publications

(165 reference statements)

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“…Amino acid positions subjected to site-directed mutagenesis are highlighted. [Colour figure can be viewed at wileyonlinelibrary.com] an aminoacyl-phosphatidylglycerol synthase, which is strictly specific for the synthesis of lysyl-phosphatidylglycerol (L-PG) when expressed in Escherichia coli (Roy and Ibba, 2009), whereas orthologous enzymes facilitate the synthesis of alanyl-PG (A-PG) using the corresponding A-PG synthase (A-PGS) or display a broad substrate specificity (Fields and Roy, 2017). Amino acids for these reactions are provided by aminoacyl-tRNAs (Roy, 2009;Fields and Roy, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…[Colour figure can be viewed at wileyonlinelibrary.com] an aminoacyl-phosphatidylglycerol synthase, which is strictly specific for the synthesis of lysyl-phosphatidylglycerol (L-PG) when expressed in Escherichia coli (Roy and Ibba, 2009), whereas orthologous enzymes facilitate the synthesis of alanyl-PG (A-PG) using the corresponding A-PG synthase (A-PGS) or display a broad substrate specificity (Fields and Roy, 2017). Amino acids for these reactions are provided by aminoacyl-tRNAs (Roy, 2009;Fields and Roy, 2017). Our laboratory contributed to the molecular understanding of the A-PGS system from the human pathogen Pseudomonas aeruginosa (Klein et al, 2009;Hebecker et al, 2011;Hebecker et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Virulence of Agrobacteriumtumefaciens requires lipid homeostasis mediated by the lysyl‐phosphatidylglycerol hydrolase AcvB

Groenewold

Hebecker

Fritz

et al. 2018

Molecular Microbiology

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Summary Agrobacterium tumefaciens transfers oncogenic T‐DNA via the type IV secretion system (T4SS) into plants causing tumor formation. The acvB gene encodes a virulence factor of unknown function required for plant transformation. Here we specify AcvB as a periplasmic lysyl‐phosphatidylglycerol (L‐PG) hydrolase, which modulates L‐PG homeostasis. Through functional characterization of recombinant AcvB variants, we showed that the C‐terminal domain of AcvB (residues 232–456) is sufficient for full enzymatic activity and defined key residues for catalysis. Absence of the hydrolase resulted in ~10‐fold increase in L‐PG in Agrobacterium membranes and abolished T‐DNA transfer and tumor formation. Overproduction of the L‐PG synthase gene (lpiA) in wild‐type A. tumefaciens resulted in a similar increase in the L‐PG content (~7‐fold) and a virulence defect even in the presence of intact AcvB. These results suggest that elevated L‐PG amounts (either by overproduction of the synthase or absence of the hydrolase) are responsible for the virulence phenotype. Gradually increasing the L‐PG content by complementation with different acvB variants revealed that cellular L‐PG levels above 3% of total phospholipids interfere with T‐DNA transfer. Cumulatively, this study identified AcvB as a novel virulence factor required for membrane lipid homeostasis and T‐DNA transfer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Virulence of Agrobacteriumtumefaciens requires lipid homeostasis mediated by the lysyl‐phosphatidylglycerol hydrolase AcvB

Groenewold

Hebecker

Fritz

et al. 2018

Molecular Microbiology

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“…MprFs are bacterial virulence factors that transfer amino acids (aa) onto membrane glycerolipids in a so-called aminoacylation reaction (4). This process requires aminoacyl-transfer RNAs (aa-tRNA) that are first synthesized by aminoacyl-tRNA synthetases (aaRS) (5), prior transfer of the aa moiety onto a lipid acceptor substrate, that is, phosphatidylglycerol, cardiolipin, or diacylglycerol (4). The aminoacyl-tRNA transferase (AAT) module, that catalyzes the transfer, belongs to the DUF2156 family and recognizes both the aa-tRNA and the lipid substrates (6).…”

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confidence: 99%

RNA-dependent sterol aspartylation in fungi

Yakobov

Fischer

Mahmoudi

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Diverting aminoacyl-transfer RNAs (tRNAs) from protein synthesis is a well-known process used by a wide range of bacteria to aminoacylate membrane constituents. By tRNA-dependently adding amino acids to glycerolipids, bacteria change their cell surface properties, which intensifies antimicrobial drug resistance, pathogenicity, and virulence. No equivalent aminoacylated lipids have been uncovered in any eukaryotic species thus far, suggesting that tRNA-dependent lipid remodeling is a process restricted to prokaryotes. We report here the discovery of ergosteryl-3β-O-l-aspartate (Erg-Asp), a conjugated sterol that is produced by the tRNA-dependent addition of aspartate to the 3β-OH group of ergosterol, the major sterol found in fungal membranes. In fact, Erg-Asp exists in the majority of “higher” fungi, including species of biotechnological interest, and, more importantly, in human pathogens likeAspergillus fumigatus. We show that a bifunctional enzyme, ergosteryl-3β-O-l-aspartate synthase (ErdS), is responsible for Erg-Asp synthesis. ErdS corresponds to a unique fusion of an aspartyl-tRNA synthetase—that produces aspartyl-tRNAAsp(Asp-tRNAAsp)—and of aDomain of Unknown Function 2156, which actually transfers aspartate from Asp-tRNAAsponto ergosterol. We also uncovered that removal of the Asp modifier from Erg-Asp is catalyzed by a second enzyme, ErdH, that is a genuine Erg-Asp hydrolase participating in the turnover of the conjugated sterol in vivo. Phylogenomics highlights that the entire Erg-Asp synthesis/degradation pathway is conserved across “higher” fungi. Given the central roles of sterols and conjugated sterols in fungi, we propose that this tRNA-dependent ergosterol modification and homeostasis system might have broader implications in membrane remodeling, trafficking, antimicrobial resistance, or pathogenicity.

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“…In addition to their vital role in protein synthesis and synthetic biology applications, tRNAs are also involved in cellular processes beyond translation. These processes include lipid aminoacylation [9] and bacterial conjugation [10]. The contributions to the special issue in this area also focused on the role of tRNA modifications in wobble decoding [11] and bacterial cell death [12].…”

Section: Trna Evolution and Modification In Microorganismsmentioning

confidence: 99%

“…The tRNA-dependent aminoacylation of bacterial outermembrane lipids confers increased virulence and resistance to cationic antimicrobial peptides. Fields et al review the known pathways to lipid aminoacylation, highlighting how enzymes from a large family of aminoacyl-phosphatidylglycerol synthases utilize aminoacyl-tRNA substrates as the amino acid donor for lipid modifications to enhance antibiotic resistance [9].…”

Section: Trna Evolution and Modification In Microorganismsmentioning

confidence: 99%