AUTHOR=Escobar Iliana E. , Possamai Rossatto Fernanda Cristina , Kim Soo Min , Kang Min Hee , Kim Wooseong , Mylonakis Eleftherios 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.675300

DOI=10.3389/fphar.2021.675300

ISSN=1663-9812

ABSTRACT=<p><italic>Staphylococcus aureus</italic> and <italic>Candida</italic> 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 <italic>S. aureus</italic> with a minimum inhibitory concentration (MIC) of 4 μg/ml. In addition, <italic>S. aureus</italic> strain MW2 did not acquire resistance to antibiotic pressure. Furthermore, Bay 11-7085 exhibited potency against <italic>Candida albicans</italic> and the emerging pathogen <italic>Candida auris</italic> 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 <italic>S. aureus</italic>), as well as antifungal-resistant <italic>Candida</italic> spp. isolates. Notably, Bay 11-7085 partially inhibited initial cell attachment and formation of a VRSA-<italic>C. albicans</italic> polymicrobial biofilm <italic>in vitro</italic>. In contrast to <italic>C. albicans</italic>, inhibition of VRSA biofilm was linked to initial cell attachment independent of its bactericidal activity. Finally, Bay 11-7085 was effective <italic>in vivo</italic> at increasing the lifespan of <italic>C. elegans</italic> during an <italic>S. aureus</italic> and a <italic>C. albicans</italic> 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.</p>