Biofilm inhibitor taurolithocholic acid alters colony morphology, specialized metabolism, and virulence of Pseudomonas aeruginosa

Abstract

Biofilm inhibition by exogenous molecules has been an attractive strategy for the development of novel therapeutics. We investigated the biofilm inhibitor taurolithocholic acid (TLCA) and its effects on the specialized metabolism, virulence and biofilm formation of the clinically relevant bacterium Pseudomonas aeruginosa strain PA14. Our study shows that TLCA alters specialized metabolism, thereby affecting P. aeruginosa colony biofilm physiology. We observed an upregulation of metabolites correlated to virulence such as the siderophore pyochelin. A wax moth virulence assay confirmed that treatment with TLCA increases virulence of P. aeruginosa. Based on our results, we believe that future endeavors to identify biofilm inhibitors must consider how a putative lead is altering the specialized metabolism of a bacterial community to prevent pathogens from entering a highly virulent state.