Postulating Modes of Action of Compounds with Antimicrobial Activities through Metabolomics Analysis

Strains of Staphylococcus aureus and coagulase-negative Staphylococcus with different antibiotic susceptibilities were selected to be the test targets of four synthesized compounds of N-aryl-4-guanidinomethylbenzoates and N-aryl-4-guanidinobenzamides. Minimum inhibitory concentrations of the four compounds showed comparable results to 13 commercial antibiotics. Metabolomics analysis based on GC-MS indicated that the four compounds shared the similar antimicrobial mechanism with clindamycin, but K-B disc diffusion tests implied that their exact binding site might be different from clindamycin or the current macrolide resistance mechanisms had no effect on the actions of synthesized compounds. The major effects of the studied compounds on the intercellular metabolites of S. aureus were the increased intracellular d-glucose, proline, phosphate and propanoic acid concentrations. This study proved metabolomics analysis was a promising tool in antibiotic mechanism research.