Anti-Pseudomonas aeruginosa compound, 1,2,3,4-tetrahydro-1,3,5-triazine derivative, exerts its action by primarily targeting MreB.

In order to find new anti-Pseudomonas agents, we carried out whole-cell based P. aeruginosa growth assay, and identified 1,2,3,4-tetrahydro-1,3,5-triazine (Compound A). This compound showed anti-Pseudomonas activity against wild as well as pumpless strain equally at a same concentration. Also, this compound was structurally very similar to A22, which is known to inhibit the bacterial actin-like protein MreB. By the analysis of resistant strains, the primary target of this compound in P. aeruginosa was definitely confirmed to be MreB. In addition, these compounds showed a bacteriostatic effect, and induced the morphology changes in P. aeruginosa from rod shape to sphere shape, which leads to be clinically favorable in terms of susceptibility to phagocytosis and release of endotoxin. These results display that Compound A is a very attractive compound which shows anti-P. aeruginosa activity based on inhibition of MreB without being affected by efflux pumps, and could provide a new step toward development of new promising anti-Pseudomonas agents, MreB inhibitors.