S-adenosylmethionine (AdoMet) functions as the primary donor in a range of methylation reactions, and is also involved in cofactor biosynthesis and radical-generating reactions. In addition, AdoMet serves as the precursor for quorum sensing molecules that trigger virulence in Gram-negative microorganism. The enzyme responsible for AdoMet synthesis has been cloned, expressed and purified from several of these infectious organisms. AdoMet synthetase from Neisseria meningitidis, Pseudomonas aeruginosa and Campylobacter jejuni shows some changes in kinetic parameters relative to the previously characterized Escherechia coli enzyme. Several alternative substrates that inhibit the virulence of the microorganism without affecting biologically essential methylation reactions have been identified. The selectivity among substrate analogs and inhibitors offers differential targeting of pathogenic Gram-negative microorganism. If successful this approach opens a potential avenue for antibiotic development that presents weaker selective pressure for resistance to develop against quorum sensing inhibition. This project is supported by a grant (AI098702) from the NIH.

Disarming infectious microorganisms through altered S-adenosylmethionine metabolism

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.