Uracil influences quorum sensing and biofilm formation in Pseudomonas aeruginosa and fluorouracil is an antagonist.
Bottom Line: Phenotypic studies confirmed uracil influences the LasR (elastase), RhlR (pyocyanin, rhamnolipids), PQS and swarming regulons.Our results also demonstrate uracil influences virulence (the pyrF mutant was less virulent to barley).Additionally, we found an anticancer uracil analogue, 5-fluorouracil, that repressed biofilm formation, abolished QS phenotypes and reduced virulence.
Affiliation: Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3122, USA.Show MeSH
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Mentions: Inhibition of biofilm formation is important as biofilms cause persistent infections that are responsible for many human diseases related to bacteria; therefore, discovering novel biofilm inhibitors is valuable. As shown in Fig. 2B, uracil regulates biofilm formation for both the pyrF mutant and wild‐type PA14; hence, we screened uracil analogues for biofilm inhibition. Among the six uracil structural analogues tested, we identified 5‐FU as an effective biofilm inhibitor (Fig. 4A). In LB medium, 5‐FU (25 µM) decreased PA14 biofilm formation threefold with a 20% reduction in the specific growth rate, and 200 µM 5‐FU inhibited biofilm formation 33‐fold with a 50% reduction in the specific growth rate (Fig. 4B). In M9 glucose medium, we found that 10 µM 5‐FU inhibited biofilm formation by 56% (Fig. 4C) without affecting growth (in planktonic cultures, final turbidity at 620 nm was 0.132 ± 0.005 without 5‐FU and 0.133 ± 0.001 with 5‐FU). At higher concentrations, 25 µM 5‐FU, biofilm formation was inhibited by 61%, but growth was also inhibited (final turbidity at 620 nm was 0.107 ± 0.001).
Affiliation: Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3122, USA.