Repurposing Kinase Inhibitor Bay 11-7085 to Combat Staphylococcus aureus and Candida albicans Biofilms

Abstract

<i>Staphylococcus aureus</i> and <i>Candida</i> spp. are commonly linked with topical biofilm-associated infections such as those found on chronic wounds. These biofilms are notoriously difficult to treat, highlighting the grave need to discover and study new broad-spectrum agents to combat associated infections. Here we report that the kinase inhibitor Bay 11-7085 exhibited bactericidal activity against multidrug-resistant <i>S. aureus</i> with a minimum inhibitory concentration (MIC) of 4 μg/ml. In addition, <i>S. aureus</i> strain MW2 did not acquire resistance to antibiotic pressure. Furthermore, Bay 11-7085 exhibited potency against <i>Candida albicans</i> and the emerging pathogen <i>Candida auris</i> with a MIC of 0.5-1 μg/ml. Bay 11-7085 partially inhibited and eradicated biofilm formation of various pathogens, such as VRSA (vancomycin-resistant <i>S. aureus</i>), as well as antifungal-resistant <i>Candida</i> spp. isolates. Notably, Bay 11-7085 partially inhibited initial cell attachment and formation of a VRSA-<i>C. albicans</i> polymicrobial biofilm <i>in vitro</i>. In contrast to <i>C. albicans</i>, inhibition of VRSA biofilm was linked to initial cell attachment independent of its bactericidal activity. Finally, Bay 11-7085 was effective <i>in vivo</i> at increasing the lifespan of <i>C. elegans</i> during an <i>S. aureus</i> and a <i>C. albicans</i> infection. Our work proposes kinase inhibitor Bay 11-7085 as a potential compound capable of combating biofilms associated with primary multidrug-resistant bacteria and yeast pathogens associated with wound infections.