(233as) Screening a Library of Commercially Available Compounds for Drugs with Novel Anti-Biofilm Activity

It is now well established that bacterial infections are often associated with biofilm phenotypes that demonstrate increased resistance to common antimicrobials. Further, due to the collective attrition of new-antibiotic development programs by the pharmaceutical industries, drug re-purposing has become an attractive alternative. In this work, we have screened 1,280 existing commercially available drugs in the Prestwick Chemical Library, some with previously unknown antimicrobial activity, against an organism that has been implicated as a causative pathogen in bacterial infections, such as burn and wound infections: Staphylococcus aureus and Pseudomonas aeruginosa. From a preliminary screen of the entire Prestwick Chemical Library at a fixed concentration of 10mM, we found 104 drugs that showed activity against planktonic S. aureus, and not surprisingly these were mostly antimicrobials and antiseptics. The activity of 18 selected non-antimicrobials observed in the preliminary screen was confirmed in dose response experiments. Finally, a selection of nine drugs with little or no reported antimicrobial activity was tested against pre-formed biofilms of S. aureus. Three of these drugs retained their antimicrobial activity against pre-formed biofilms making them attractive candidates for repurposing as novel anti-biofilm therapies. On the other hand P. aeruginosa biofilms were resistant to most of the drugs in the library. However, combinations of some of the drugs in the library with sub-inhibitory concentrations of antibiotics and surfactants were effective against the biofilms. Together, our data show that the anti-biofilm activity makes these drugs attractive candidates for re-purposing as novel anti-biofilm therapies, especially in combination with traditional antimicrobials, and warrant further attention to determine their modes of action.