The cellular envelope is the first layer of defense protecting the cell from the hostilities of the surrounding environment. In order to thrive in their ever-changing environmental conditions, bacteria have developed mechanisms to adapt the biochemical properties of their membranes in response to environmental cues. Aminoacyl-phosphatidylglycerol synthases (aaPGSs) are integral membrane proteins responsible for the biosynthesis of aminoacyl-phosphatidylglycerol (aa-PG) in the cytoplasmic membrane of various bacteria. These enzymes divert several aminoacyl-tRNAs (aa-tRNAs) from their normal use in protein biosynthesis and utilize the amino acids of these charged tRNAs for the modification of the polar head of the phosphatidylglycerol (PG) constituting the cytoplasmic membrane. Addition of amino acids to the glycerol moiety of PG decreases the net negative charge of the membrane, thereby lowering the cellular permeability to cationic molecules and altering the physiological properties of the bacterial envelope. In Staphylococcus aureus, lysylated PG confers resistance to cationic antibacterial agents such as the pore forming peptides produced by the innate immune response during host infection (e.g., defensins produced by human neutrophils), and provides resistance to several other cationic antimicrobials (i.e., aminoglycosides, betalactamines and glycopeptides). aa-PGs not only provide bacteria with resistance to cationic antimicrobial agents and host defenses during infection, but also to other environmental stressors such as those encountered during extreme osmotic or acidic conditions.
Understanding the mechanisms of cell membrane permeation by antibiotics and the strategies utilized by bacteria to resist these antibiotics is crucial for the design of antimicrobial agents that target not only aaPGSs and their regulatory mechanisms, but also individual components of the remodeled membrane. The focus of our research is to define the structure-function relationship of aaPGS family members from a variety of microorganisms and to determine the extent of the different amino acids utilized by these enzymes for lipid modification. These studies will provide insight into the biological significance of aa-PGs and the role of these modified lipids in bacterial pathogenicity and environmental adaptation.
Recent publications:
  1. Grube CD, Roy H. A Quantitative Spectrophotometric Assay to Monitor the tRNA-Dependent Pathway for Lipid Aminoacylation In Vitro. Journal of biomolecular screening. 2016; 21(7):722-8. PMID:27073192

  2. Smith AM, Harrison JS, Grube CD, Sheppe AE, Sahara N, Ishii R, Nureki O, Roy H. tRNA-dependent alanylation of diacylglycerol and phosphatidylglycerol in Corynebacterium glutamicum. Molecular microbiology. 2015; 98(4):681-93. NIHMSID: NIHMS733861 PMID:26235234  PMCID:PMC4639916

  3. Dare K, Shepherd J, Roy H, Seveau S, Ibba M. LysPGS formation in Listeria monocytogenes has broad roles in maintaining membrane integrity beyond antimicrobial peptide resistance. Virulence. 2014; 5(4):534-46. PMID:24603093  PMCID:PMC4063814

  4. Smith, A. M., Harrison, J. S., Sprague, K. M., and Roy, H. (2013)A conserved hydrolase responsible for the cleavage of aminoacylphosphatidylglycerol in the membrane of Enterococcus faecium. J. Biol. Chem. 288, 22768-22776

  5. Lorber B, Fischer F, Bailly M, Roy H, Kern D. Protein analysis by dynamic light scattering: methods and techniques for students. Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology. 2012; 40(6):372-82. PMID:23166025

  6. Zou SB, Hersch SJ, Roy H, Wiggers JB, Leung AS, Buranyi S, Xie JL, Dare K, Ibba M, and Navarre WW,  Loss of elongation factor P disrupts bacterial outer membrane integrity. J Bacteriol, 2012. 194(2): 413-425.
  7. Rogers TE, Ataide SF, Dare K, Katz A, Seveau S, Roy H, Ibba M. A pseudo-tRNA modulates antibiotic resistance in Bacillus cereus. PloS one. 2012; 7(7):e41248. PMID:22815980  PMCID:PMC3399842

  8. Zou SB, Roy H, Ibba M, and Navarre WW, Elongation factor P mediates a novel post-transcriptional regulatory pathway critical for bacterial virulence. Virulence, 2011. 2(2): 147-51.
  9. Roy H, Zou SB, Bullwinkle TJ, Wolfe BS, Gilreath MS, Forsyth CJ, Navarre WW, and Ibba M, The tRNA synthetase paralog PoxA modifies elongation factor-P with (R)-beta-lysine. Nat Chem Biol, 2011. 7(10): 667-9.
  10. Gilreath MS, Roy H, Bullwinkle TJ, Katz A, Navarre WW, and Ibba M, beta-Lysine discrimination by lysyl-tRNA synthetase. FEBS Lett, 2011. 585(20): 3284-8.
  11. Blaise M, Frechin M, Olieric V, Charron C, Sauter C, Lorber B, Roy H, and Kern D, Crystal Structure of the Archaeal Asparagine Synthetase: Interrelation with Aspartyl-tRNA and Asparaginyl-tRNA Synthetases. J Mol Biol, 2011. 412(3): 437-52.
  12. Banerjee R, Reynolds NM, Yadavalli SS, Rice C, Roy H, Banerjee P, Alexander RW, and Ibba M, Mitochondrial Aminoacyl-tRNA Synthetase Single-Nucleotide Polymorphisms That Lead to Defects in Refolding but Not Aminoacylation. J Mol Biol, 2011. 410(2): 280-93.
  13. Roy H and Ibba M, Bridging the gap between ribosomal and nonribosomal protein synthesis. Proc Natl Acad Sci U S A, 2010. 107(33): 14517-8.
  14. Reynolds NM, Ling J, Roy H, Banerjee R, Repasky SE, Hamel P, and Ibba M, Cell-specific differences in the requirements for translation quality control. Proc Natl Acad Sci U S A, 2010. 107(9): 4063-8.
  15. Navarre WW, Zou SB, Roy H, Xie JL, Savchenko A, Singer A, Edvokimova E, Prost LR, Kumar R, Ibba M, and Fang FC, PoxA, yjeK, and elongation factor P coordinately modulate virulence and drug resistance in Salmonella enterica. Mol Cell, 2010. 39(2): 209-21.
  16. Banerjee R, Chen S, Dare K, Gilreath M, Praetorius-Ibba M, Raina M, Reynolds NM, Rogers T, Roy H, Yadavalli SS, and Ibba M, tRNAs: cellular barcodes for amino acids. FEBS Lett, 2010. 584(2): 387-95.
  17. Zeng Y, Roy H, Preeti BP, Ibba M, and Chen S, Characterization of two seryl-tRNA synthetases in albomycin-producing Streptomyces sp. ATCC 700974. Antimicrob Agents Chemother, 2009. 53(11): 4619-27.
  18. Roy H and Ibba M, Broad range amino acid specificity of RNA-dependent lipid remodeling by multiple peptide resistance factors. J Biol Chem, 2009. 284(43): 29677-83.
  19. Roy H, Dare K, and Ibba M, Adaptation of the bacterial membrane to changing environments using aminoacylated phospholipids. Mol Microbiol, 2009. 71(3): 547-50.
  20. Roy H, Tuning the properties of the bacterial membrane with aminoacylated phosphatidylglycerol. IUBMB life, 2009. 61(10): 940-953.
  21. Ling J, So BR, Yadavalli SS, Roy H, Shoji S, Fredrick K, Musier-Forsyth K, and Ibba M, Resampling and editing of mischarged tRNA prior to translation elongation. Mol Cell, 2009. 33(5): 654-60.
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