Cargando…

Killing of Staphylococcus aureus persisters by a multitarget natural product chrysomycin A

Staphylococcus aureus poses a severe public health problem as one of the vital causative agents of healthcare- and community-acquired infections. There is a globally urgent need for new drugs with a novel mode of action (MoA) to combat S. aureus biofilms and persisters that tolerate antibiotic treat...

Descripción completa

Detalles Bibliográficos
Autores principales: Jia, Jia, Zheng, Mingxin, Zhang, Chongwen, Li, Binglei, Lu, Cai, Bai, Yuefan, Tong, Qian, Hang, Xudong, Ge, Yixin, Zeng, Liping, Zhao, Ming, Song, Fuhang, Zhang, Huawei, Zhang, Liang, Hong, Kui, Bi, Hongkai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403215/
https://www.ncbi.nlm.nih.gov/pubmed/37540745
http://dx.doi.org/10.1126/sciadv.adg5995
_version_ 1785085021210542080
author Jia, Jia
Zheng, Mingxin
Zhang, Chongwen
Li, Binglei
Lu, Cai
Bai, Yuefan
Tong, Qian
Hang, Xudong
Ge, Yixin
Zeng, Liping
Zhao, Ming
Song, Fuhang
Zhang, Huawei
Zhang, Liang
Hong, Kui
Bi, Hongkai
author_facet Jia, Jia
Zheng, Mingxin
Zhang, Chongwen
Li, Binglei
Lu, Cai
Bai, Yuefan
Tong, Qian
Hang, Xudong
Ge, Yixin
Zeng, Liping
Zhao, Ming
Song, Fuhang
Zhang, Huawei
Zhang, Liang
Hong, Kui
Bi, Hongkai
author_sort Jia, Jia
collection PubMed
description Staphylococcus aureus poses a severe public health problem as one of the vital causative agents of healthcare- and community-acquired infections. There is a globally urgent need for new drugs with a novel mode of action (MoA) to combat S. aureus biofilms and persisters that tolerate antibiotic treatment. We demonstrate that a benzonaphthopyranone glycoside, chrysomycin A (ChryA), is a rapid bactericide that is highly active against S. aureus persisters, robustly eradicates biofilms in vitro, and shows a sustainable killing efficacy in vivo. ChryA was suggested to target multiple critical cellular processes. A wide range of genetic and biochemical approaches showed that ChryA directly binds to GlmU and DapD, involved in the biosynthetic pathways for the cell wall peptidoglycan and lysine precursors, respectively, and inhibits the acetyltransferase activities by competition with their mutual substrate acetyl-CoA. Our study provides an effective antimicrobial strategy combining multiple MoAs onto a single small molecule for treatments of S. aureus persistent infections.
format Online
Article
Text
id pubmed-10403215
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher American Association for the Advancement of Science
record_format MEDLINE/PubMed
spelling pubmed-104032152023-08-05 Killing of Staphylococcus aureus persisters by a multitarget natural product chrysomycin A Jia, Jia Zheng, Mingxin Zhang, Chongwen Li, Binglei Lu, Cai Bai, Yuefan Tong, Qian Hang, Xudong Ge, Yixin Zeng, Liping Zhao, Ming Song, Fuhang Zhang, Huawei Zhang, Liang Hong, Kui Bi, Hongkai Sci Adv Biomedicine and Life Sciences Staphylococcus aureus poses a severe public health problem as one of the vital causative agents of healthcare- and community-acquired infections. There is a globally urgent need for new drugs with a novel mode of action (MoA) to combat S. aureus biofilms and persisters that tolerate antibiotic treatment. We demonstrate that a benzonaphthopyranone glycoside, chrysomycin A (ChryA), is a rapid bactericide that is highly active against S. aureus persisters, robustly eradicates biofilms in vitro, and shows a sustainable killing efficacy in vivo. ChryA was suggested to target multiple critical cellular processes. A wide range of genetic and biochemical approaches showed that ChryA directly binds to GlmU and DapD, involved in the biosynthetic pathways for the cell wall peptidoglycan and lysine precursors, respectively, and inhibits the acetyltransferase activities by competition with their mutual substrate acetyl-CoA. Our study provides an effective antimicrobial strategy combining multiple MoAs onto a single small molecule for treatments of S. aureus persistent infections. American Association for the Advancement of Science 2023-08-04 /pmc/articles/PMC10403215/ /pubmed/37540745 http://dx.doi.org/10.1126/sciadv.adg5995 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Jia, Jia
Zheng, Mingxin
Zhang, Chongwen
Li, Binglei
Lu, Cai
Bai, Yuefan
Tong, Qian
Hang, Xudong
Ge, Yixin
Zeng, Liping
Zhao, Ming
Song, Fuhang
Zhang, Huawei
Zhang, Liang
Hong, Kui
Bi, Hongkai
Killing of Staphylococcus aureus persisters by a multitarget natural product chrysomycin A
title Killing of Staphylococcus aureus persisters by a multitarget natural product chrysomycin A
title_full Killing of Staphylococcus aureus persisters by a multitarget natural product chrysomycin A
title_fullStr Killing of Staphylococcus aureus persisters by a multitarget natural product chrysomycin A
title_full_unstemmed Killing of Staphylococcus aureus persisters by a multitarget natural product chrysomycin A
title_short Killing of Staphylococcus aureus persisters by a multitarget natural product chrysomycin A
title_sort killing of staphylococcus aureus persisters by a multitarget natural product chrysomycin a
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403215/
https://www.ncbi.nlm.nih.gov/pubmed/37540745
http://dx.doi.org/10.1126/sciadv.adg5995
work_keys_str_mv AT jiajia killingofstaphylococcusaureuspersistersbyamultitargetnaturalproductchrysomycina
AT zhengmingxin killingofstaphylococcusaureuspersistersbyamultitargetnaturalproductchrysomycina
AT zhangchongwen killingofstaphylococcusaureuspersistersbyamultitargetnaturalproductchrysomycina
AT libinglei killingofstaphylococcusaureuspersistersbyamultitargetnaturalproductchrysomycina
AT lucai killingofstaphylococcusaureuspersistersbyamultitargetnaturalproductchrysomycina
AT baiyuefan killingofstaphylococcusaureuspersistersbyamultitargetnaturalproductchrysomycina
AT tongqian killingofstaphylococcusaureuspersistersbyamultitargetnaturalproductchrysomycina
AT hangxudong killingofstaphylococcusaureuspersistersbyamultitargetnaturalproductchrysomycina
AT geyixin killingofstaphylococcusaureuspersistersbyamultitargetnaturalproductchrysomycina
AT zengliping killingofstaphylococcusaureuspersistersbyamultitargetnaturalproductchrysomycina
AT zhaoming killingofstaphylococcusaureuspersistersbyamultitargetnaturalproductchrysomycina
AT songfuhang killingofstaphylococcusaureuspersistersbyamultitargetnaturalproductchrysomycina
AT zhanghuawei killingofstaphylococcusaureuspersistersbyamultitargetnaturalproductchrysomycina
AT zhangliang killingofstaphylococcusaureuspersistersbyamultitargetnaturalproductchrysomycina
AT hongkui killingofstaphylococcusaureuspersistersbyamultitargetnaturalproductchrysomycina
AT bihongkai killingofstaphylococcusaureuspersistersbyamultitargetnaturalproductchrysomycina