Repurposing sunscreen as an antibiotic: zinc-activated avobenzone inhibits methicillin-resistant Staphylococcus aureus

Author:

Andrews Rachel M1ORCID,Bollar Gretchen E1,Giattina A Sophia1,Dalecki Alex G1,Wallace Jr John R1,Frantz Leah1,Eschliman Kayla2,Covarrubias-Zambrano Obdulia23,Keith Johnathan D1,Duverger Alexandra1,Wagner Frederic1,Wolschendorf Frank1,Bossmann Stefan H23,Birket Susan E1,Kutsch Olaf1

Affiliation:

1. School of Medicine, The University of Alabama at Birmingham , Birmingham, AL , USA

2. Department of Chemistry, Kansas State University , Kansas City, KS , USA

3. Department of Cancer Biology, The University of Kansas Medical Center , Kansas City, KS , USA

Abstract

Abstract Methicillin-resistant Staphylococcus aureus (MRSA) is a major healthcare concern with associated healthcare costs reaching over ${\$}$1 billion in a single year in the USA. Antibiotic resistance in S. aureus is now observed against last line of defense antibiotics, such as vancomycin, linezolid, and daptomycin. Unfortunately, high throughput drug discovery approaches to identify new antibiotics effective against MRSA have not resulted in much tangible success over the last decades. Previously, we demonstrated the feasibility of an alternative drug discovery approach, the identification of metallo-antibiotics, compounds that gain antibacterial activity only after binding to a transition metal ion and as such are unlikely to be detected in standard drug screens. We now report that avobenzone, the primary active ingredient of most sunscreens, can be activated by zinc to become a potent antibacterial compound against MRSA. Zinc-activated avobenzone (AVB-Zn) potently inhibited a series of clinical MRSA isolates [minimal inhibitory concentration (MIC): 0.62–2.5 µM], without pre-existing resistance and activity without zinc (MIC: >10 µM). AVB-Zn was also active against clinical MRSA isolates that were resistant against the commonly used zinc–salt antibiotic bacitracin. We found AVB-Zn exerted no cytotoxicity on human cell lines and primary cells. Last, we demonstrate AVB-Zn can be deployed therapeutically as lotion preparations, which showed efficacy in a mouse wound model of MRSA infection. AVB-Zn thus demonstrates Zn-activated metallo-antibiotics are a promising avenue for future drug discovery.

Funder

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Metals and Alloys,Biochemistry,Biomaterials,Biophysics,Chemistry (miscellaneous)

Reference69 articles.

1. Global Burden of Bacterial Antimicrobial Resistance in 2019: a Systematic Analysis;Murray;Lancet,2022

2. Platforms for Antibiotic Discovery;Lewis;Nat. Rev. Drug. Discov.,2013

3. Gepotidacin: a Novel, Oral, ‘First-in-Class’ Triazaacenaphthylene Antibiotic for the Treatment of Uncomplicated Urinary Tract Infections and Urogenital Gonorrhoea;Watkins;J. Antimicrob. Chemother.,2023

4. Design of Two Phase III, Randomized, Multicenter Studies Comparing Gepotidacin with Nitrofurantoin for the Treatment of Uncomplicated Urinary Tract Infection in Female Participants;Perry;Infect. Dis. Ther.,2022

5. Dose Selection for Phase III Clinical Evaluation of Gepotidacin (GSK2140944) in the Treatment of Uncomplicated Urinary Tract Infections;Scangarella-Oman Nicole;Antimicrob. Agents Chemother.,2022

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Conformers influence on UV-absorbance of avobenzone;Journal of Photochemistry and Photobiology A: Chemistry;2024-08

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3