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

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

doi:10.3389/fphar.2021.675300

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

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

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

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

Original language	English
Article number	675300
Journal	Frontiers in Pharmacology
Volume	12
DOIs	https://doi.org/10.3389/fphar.2021.675300
State	Published - 5 May 2021

Bibliographical note

Funding Information:
This research was funded by NIH grant P01 AI083214 to EM IE was supported by sub-award 530804. WK is supported by the National Research Foundation of Korea Grants funded by the Korea government (MSIT) (2020R1C1C1008842, 2018R1A5A2025286 and 2017M3A9E4077234). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in, or financial conflict with, the subject matter or materials discussed in the manuscript, apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Publisher Copyright:
© Copyright © 2021 Escobar, Possamai Rossatto, Kim, Kang, Kim and Mylonakis.

Keywords

Bay 11-7085
C. elegans high through-put screening
Candida albicans
Staphylococcus aureus
antibiotic resistance
biofilms

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

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

keywords = "Bay 11-7085, C. elegans high through-put screening, Candida albicans, Staphylococcus aureus, antibiotic resistance, biofilms",

author = "Escobar, {Iliana E.} and {Possamai Rossatto}, {Fernanda Cristina} and Kim, {Soo Min} and Kang, {Min Hee} and Wooseong Kim and Eleftherios Mylonakis",

note = "Funding Information: This research was funded by NIH grant P01 AI083214 to EM IE was supported by sub-award 530804. WK is supported by the National Research Foundation of Korea Grants funded by the Korea government (MSIT) (2020R1C1C1008842, 2018R1A5A2025286 and 2017M3A9E4077234). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in, or financial conflict with, the subject matter or materials discussed in the manuscript, apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Escobar, Possamai Rossatto, Kim, Kang, Kim and Mylonakis.",

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N2 - Staphylococcus aureus and Candida 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 S. aureus with a minimum inhibitory concentration (MIC) of 4 μg/ml. In addition, S. aureus strain MW2 did not acquire resistance to antibiotic pressure. Furthermore, Bay 11-7085 exhibited potency against Candida albicans and the emerging pathogen Candida auris 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 S. aureus), as well as antifungal-resistant Candida spp. isolates. Notably, Bay 11-7085 partially inhibited initial cell attachment and formation of a VRSA-C. albicans polymicrobial biofilm in vitro. In contrast to C. albicans, inhibition of VRSA biofilm was linked to initial cell attachment independent of its bactericidal activity. Finally, Bay 11-7085 was effective in vivo at increasing the lifespan of C. elegans during an S. aureus and a C. albicans 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.

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

Abstract

Bibliographical note

Keywords

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