Screening a Commercial Library of Pharmacologically Active Small Molecules Against Staphylococcus aureus Biofilms

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 repurposing is 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 Staphylococcus aureus, one of the commonly encountered causative pathogen of burn and wound infections. From the primary screen of the entire Prestwick Chemical Library at a fixed concentration of 10μM, 104 drugs were found to be effective against planktonic S. aureus , and not surprisingly, these were mostly antimicrobials and antiseptics. The activity of 18 selected repurposing candidates, that is, drugs that show antimicrobial activity that are not already considered antimicrobials, observed in the primary screen was confirmed in dose response experiments. Finally, a subset of nine of these drug candidates was tested against pre-formed biofilms of S. aureus . We found that three of these drugs, Niclosamide, Carmofur, and Auranofin, possessed antimicrobial activity against pre-formed biofilms, making them attractive candidates for repurposing as novel anti-biofilm therapies.