![]() ![]() The staphylococcal two-component system SrrA/B was shown to be an antibacterial target of coenzyme Q1. aureus to cause toxic shock syndrome in a rabbit model, inhibited the growth of four Gram-negative bacteria, and synergized with another antimicrobial agent, glycerol monolaurate, to inhibit S. Menadione, 1,4-naphthoquinone, and coenzymes Q1 to Q3 but not menaquinone, phylloquinone, or coenzyme Q10 inhibited the growth and to a greater extent exotoxin production of Staphylococcus aureus, Bacillus anthracis, Streptococcus pyogenes, and Streptococcus agalactiae at concentrations of 10 to 200 μg/ml. We initiated studies with four of these organisms to develop novel topical antibacterial agents that interfere with growth and exotoxin production, focusing on menaquinone analogs. Gram-positive bacteria cause serious human illnesses through combinations of cell surface and secreted virulence factors. Schlievert, Patrick M Merriman, Joseph A Salgado-Pabón, Wilmara Mueller, Elizabeth A Spaulding, Adam R Vu, Bao G Chuang-Smith, Olivia N Kohler, Petra L Kirby, John R ![]() Menaquinone analogs inhibit growth of bacterial pathogens. The most potent compound inhibits MenE with an IC50 value of 5.7 μM. We report herein a series of mechanism-based inhibitors of MenE, an acyl-CoA synthetase that catalyzes adenylation and thioesterification of o-succinylbenzoic acid (OSB) during menaquinone biosynthesis. Menaquinone (vitamin K2) is an essential component of the electron transfer chain in many pathogens, including Mycobacterium tuberculosis and Staphylococcus aureus, and menaquinone biosynthesis is a potential target for antibiotic drug discovery. ![]() Lu, Xuequan Zhang, Huaning Tonge, Peter J. Mechanism-based inhibitors of MenE, an acyl-CoA synthetase involved in bacterial menaquinone biosynthesis†![]()
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