Anti-biofilm and Anti-Virulence Efficacy of Celastrol Against <i>Stenotrophomonas maltophilia</i>

<i>Stenotrophomonas maltophilia</i> is a multi-drug resistant opportunistic pathogen that causes nosocomial infections in immunocompromised patients. This pathogen is difficult to treat owing to its intrinsic multidrug resistance and ability to form antimicrobial-tolerant biofilms. In the present study, we aimed to assess the potential use of celastrol as a novel anti-biofilm and/or anti-virulence agent against <i>S. maltophilia</i>. Results showed that celastrol at its sub-inhibitory doses decreased biofilm formation and disrupt the established biofilms produced by <i>S. maltophilia</i>. Celastrol-induced decrease in biofilm formation was dose-dependent based on the results of the microtiter plate biofilm assays and confocal laser scanning microscopy. In addition, our data validated the anti-virulence efficacy of celastrol, wherein it significantly interfered with the production of protease and motility of <i>S. maltophilia</i>. To support these phenotypic results, transcriptional analysis revealed that celastrol down-regulated the expression of biofilm- and virulence- associated genes (<i>smeYZ</i>, <i>fsnR</i>, and <i>bfmAK</i>) in <i>S. maltophilia</i>. Interestingly, celastrol significantly inhibited the expression of <i>smeYZ</i> gene, which encodes the resistance-nodulation-division (RND)-type efflux pump, SmeYZ. Overall, our findings suggested that celastrol might be a promising bioactive agent for treatment of biofilm- and virulence-related infections caused by the multi-drug resistant <i>S. maltophilia</i>.