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Showing papers by "Ian Chopra published in 1999"


Journal ArticleDOI
TL;DR: The presence of l-lysine in precursors containing amino acids added after the reaction catalyzed by the MurE ligase provided additional information about the specificity of the enzymes involved in these latter processes.
Abstract: The monomer units in the Escherichia coli and Staphylococcus aureus cell wall peptidoglycans differ in the nature of the third amino acid in the L-alanyl-gamma-D-glutamyl-X-D-alanyl-D-alanine side chain, where X is meso-diaminopimelic acid or L-lysine, respectively. The murE gene from S. aureus encoding the UDP-N-acetylmuramoyl-L-alanyl-D-glutamate: L-lysine ligase was identified and cloned into plasmid vectors. Induction of its overexpression in E. coli rapidly results in abnormal morphological changes and subsequent cell lysis. A reduction of 28% in the peptidoglycan content was observed in induced cells, and analysis of the peptidoglycan composition and structure showed that ca. 50% of the meso-diaminopimelic acid residues were replaced by L-lysine. Lysine was detected in both monomer and dimer fragments, but the acceptor units from the latter contained exclusively meso-diaminopimelic acid, suggesting that no transpeptidation could occur between the epsilon-amino group of L-lysine and the alpha-carboxyl group of D-alanine. The overall cross-linking of the macromolecule was only slightly decreased. Detection and analysis of meso-diaminopimelic acid- and L-lysine-containing peptidoglycan precursors confirmed the presence of L-lysine in precursors containing amino acids added after the reaction catalyzed by the MurE ligase and provided additional information about the specificity of the enzymes involved in these latter processes.

62 citations


Journal ArticleDOI
Ian Chopra1
TL;DR: Despite observations from several studies that antisense agents can interfere with bacterial gene expression in a sequence specific manner, their uptake into bacteria is poor, which is a limiting factor in their potential application as therapeutic agents for bacterial infections.
Abstract: Antisense agents have received widespread interest as potential therapeutic agents for a number of diseases, including cancer, inflammatory conditions and viral infections. However, less emphasis has been placed on their potential application in the therapy of bacterial infections. This review considers the reported effects of backbone modified oligonucleotides (phosphorothioate and methyl phosphonate analogues) as well as peptide nucleic acids (PNAs) on gene expression and bacterial growth. In addition to suppressing bacterial growth by decreasing the expression of essential genes, it is also evident that antisense agents can be specifically targeted to genes that control expression of antibiotic resistance mechanisms, thereby potentially restoring an antibiotic-sensitive phenotype to the cell. Despite observations from several studies that antisense agents can interfere with bacterial gene expression in a sequence specific manner, their uptake into bacteria is poor. At present this is a limiting factor ...

8 citations