Staphylococcus aureus 5-lysin

Peschel, A., Jack, R., Otto, M., Collins, L., Staubitz, P., Nicholson, G., Kalbacher, H., Nieuwenhuizen, W., Jung, G., Tarkowski, A., van Kessel, K., van Strijp, J. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with 1-lysine. J Exp Med 193 (2001) 1067-1076. 

The peptides in the accumulated uridine nucleotides from another penicillin-inhibited strain of Staphylococcus aureus have been shown - to contain alanine, glycine, lysine, aspartic acid, and glutamic acid in various combinations. The most complex peptide contained alanine, lysine, glycine, glutamic acid, and aspartic acid in the ratios 2 2 2 1 1. All of these amino acids were present in hydrolyzates from the bacterial cell-wall of the strain. 

Enzymes in the aaRS family are a promising target for the development of novel antibiotics (17). Selective inhibition of just one essential aaRS would be lethal to the pathogen. The best example is mupirocin, a commercially marketed IleRS inhibitor. Mupirocin, also known as pseudomonic acid, originally was isolated from Pseudomonas fluorescens and is used as a topical antibiotic against gram-positive bacteria, particularly Staphylococcus aureus. It binds directly to the first lysine of the conserved KMSKS sequence in the amino acylation active site (18). 

Inactivation of certain enzyme systems involved in the oxidative metabolism of sensitive organisms by polymyxin and colistin has also been reported. This, however, might be a secondary effect . Bacitracin has been reported to interfere with cell wall synthesis. It causes Staphylococcus aureus to lyse , to form protoplasts and to accumulate cell wall precursors " . The incorporation of radioactive amino acids into cell wall mucopeptides is inhibited. Bacitracin has further been found to prevent Staphylococcus aureus from synthesizing /3-galactosidase , yet it does not interfere with the incorporation of radioactive lysine into cells . In experiments with Staphylococcus aureus, bacitracin and penicillin were shown to share a common binding site on the membrane , a result which could not be confirmed in similar experiments with B. megateriumP . Recently a direct effect of bacitracin on the cytoplasmic membrane has been demonstrated, and it was suggested that the inhibition of cell wall synthesis could be a secondary effect . ... 

Fig. 3.—Schematic Structure of the Peptidoglycan from Staphylococcus aureus. [MurNAc, N-acetylmuramic acid GNAc, 2-acetamido-2-deoxy-D-glucose Ala, alanine Glu, glutamic acid Lys, lysine Gly, glycine. Arrows (— and — ) show glycosidic and peptide linkages, respectively. In the latter, arrows are drawn from the amino acid supplying the carboxyl group to the amino acid supplying the amino group.]...

Janzon L, Lofdahl S, Arvidson S (1989) Identification and nucleotide sequence of the delta-lysin gene, hid, adjacent to the accessory gene regulator (agr) of Staphylococcus aureus. Mol Gen Genet 70 337-349... 

Janzon L, Arvidson S (1990) The role of the 6-lysin gene (hid) in the regulation of virulence genes by the accessory gene regulator (agr) in Staphylococcus aureus, EMBO J... 

Harris, L., Tosatti, S., Wieland, M., Textor, M., Richards, R., 2004. Staphylococcus aureus adhesion to titanium oxide surfaces coated with non-functionalized and peptide-functionalized poly(L-lysine)-grafted-poly(ethylene glycol) copolymers. Biomaterials 25, 4135-4148. 

The occurrence of amino acids in the uridine nucleotides originally isolated by Park suggests that these compounds are involved in the activation or condensation of amino acids, but no enzymatic reactions of these compounds are known. A specific function in the formation of bacterial cell walls has been suggested following the finding of similar ratios of D-glutamic acid, D- and u-alanine, lysine, and amino sugar (1 3 1 1) in cell walls and a uridine nucleotide, both isolated from Staphylococcus aureus. ... 

FlO. 4, The nucleotide precursors UDP-GlNAc and UDP-MurNAc-pentapeptide in Staphylococcus aureus. Note that D-glutamic acid is linked to the a-amino group of L-lysine through its y-carboxyl group and that the a-carboxyl group of E)-glutaniic acid is free. The same precursors are found in Escherichia coli except that meso-diaminopimelic acid replaces L-lysine. 

Staphylococcus aureus and Strep, faecalis contain considerable amounts of potassium (approximately 100 mmoles K/lOO mg. dry weight of cells) and about one-tenth of this amount of sodium. Investigations of the changes in sodium and potassium content of the cells during the accumulation of lysine have been made by Davies, Folkes, Gale, and Bigger (1953). The accumulation of lysine by Strep, faecalis is accompanied by... 

FIGURE 3.10 Bacterial cell wall, (a) Repeating disaccharide of peptidoglycan. (b) Structure of the peptidoglycan of Staphylococcus aureus. O, L-alanine , D-alanine A, D-glutamine , L-lysine V, L-glycine... 

Pastagia, M., Euler, C., Chahales, R, Fuentes-Duculan, J., Kmeger, J.G., Fischetti, V.A., 2011. A novel chimeric lysin shows superiority to mupirocin for skin decolonization of metbicilUn-resistant and -sensitive Staphylococcus aureus strains. Antimicrob. Agents Chemother. 55, 738-744. 

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