Anti-biofilm effect of novel thiazole acid analogs against Pseudomonas aeruginosa through IQS pathways

IQS has been proven to be a new quorum sensing (QS) system against bacterial biofilm formation, which is activated in the common phosphate-limiting environment of infected tissues taking over the central las system. Up to now, numerous biofilm inhibitors which function by affecting traditional QS system have been reported. However, no compound has been reported to exert anti-biofilm activity through IQS system. Herein, various novel IQS derivatives were synthesized by the reaction of thiazole-4-carboxylic acid with different linear alcohols (R-OH) or amines (R-NH2). IQS derivatives with four carbon chain length of R group were found to present the best biofilm inhibition activity. Compound B-11 as the model molecule was observed to inhibit biofilm formation only under phosphate-limiting condition, and increase in B-11 concentration significantly reduced the expression of rhlA-gfp and pqsA-gfp, but lasB-gfp. Moreover, B-11 reduced production of virulence factors of rhamnolipid and pyocyanin under phosphate limitation. These observations indicated that the synthesized compounds possessed the anti-biofilm activity through IQS pathways rather than traditional QS pathways, which pave a path for future molecular design against bacterial biofilm formation.