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IG1, a Mansonone F Analog, Exhibits Antibacterial Activity against Staphylococcus aureus by Potentially Impairing Cell Wall Synthesis and DNA Replication

Infection caused by Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is very common in communities and hospitals, which poses a great challenge to human health. Therefore, increasing attention has been paid to finding effective antimicrobial agents. Mansonone F is a natural...

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Autores principales: Chen, Xin, Lin, Yueqiao, Gao, Qianqian, Huang, Shiliang, Zhang, Zihua, Li, Nan, Zong, Xin, Guo, Xuemin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697348/
https://www.ncbi.nlm.nih.gov/pubmed/36431037
http://dx.doi.org/10.3390/life12111902
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author Chen, Xin
Lin, Yueqiao
Gao, Qianqian
Huang, Shiliang
Zhang, Zihua
Li, Nan
Zong, Xin
Guo, Xuemin
author_facet Chen, Xin
Lin, Yueqiao
Gao, Qianqian
Huang, Shiliang
Zhang, Zihua
Li, Nan
Zong, Xin
Guo, Xuemin
author_sort Chen, Xin
collection PubMed
description Infection caused by Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is very common in communities and hospitals, which poses a great challenge to human health. Therefore, increasing attention has been paid to finding effective antimicrobial agents. Mansonone F is a natural compound which has an oxaphenalene skeleton and anti-S. aureus activity, but its sources are limited and its synthesis is difficult. Thus, IG1, a C9-substituent mansonone F analog, was assessed for its activity against Staphylococcus aureus and its mechanism of action was investigated. Antimicrobial susceptibility assays showed that IG1 has strong antibacterial activity against S. aureus, including MRSA, with minimum inhibitory concentrations (MICs) ranging from 0.5 to 2 μg/mL, which were very close to those of vancomycin, and these changed little, even with an increase in the amount of the inoculum. To further explore the antibacterial properties of IG1, time–kill experiments were conducted. Compared with vancomycin and moxifloxacin, treatment with different concentrations of IG1 reduced the viability of organisms in a very similar manner and the reduction was not significant, which indicated that IG1 is a potentially strong anti-S. aureus agent. Finally, the antibacterial mechanism was analyzed, with flow cytometric analysis revealing that IG1 treatment resulted in a time-dependent decrease in the DNA content of S. aureus. Transmission electron microscopy (TEM) analysis showed that very few dividing cells could be found and the cell wall was damaged in the field of IG1-treated cells. These results indicate that IG1 is a potential new antibacterial agent against S. aureus, including MRSA.
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spelling pubmed-96973482022-11-26 IG1, a Mansonone F Analog, Exhibits Antibacterial Activity against Staphylococcus aureus by Potentially Impairing Cell Wall Synthesis and DNA Replication Chen, Xin Lin, Yueqiao Gao, Qianqian Huang, Shiliang Zhang, Zihua Li, Nan Zong, Xin Guo, Xuemin Life (Basel) Article Infection caused by Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is very common in communities and hospitals, which poses a great challenge to human health. Therefore, increasing attention has been paid to finding effective antimicrobial agents. Mansonone F is a natural compound which has an oxaphenalene skeleton and anti-S. aureus activity, but its sources are limited and its synthesis is difficult. Thus, IG1, a C9-substituent mansonone F analog, was assessed for its activity against Staphylococcus aureus and its mechanism of action was investigated. Antimicrobial susceptibility assays showed that IG1 has strong antibacterial activity against S. aureus, including MRSA, with minimum inhibitory concentrations (MICs) ranging from 0.5 to 2 μg/mL, which were very close to those of vancomycin, and these changed little, even with an increase in the amount of the inoculum. To further explore the antibacterial properties of IG1, time–kill experiments were conducted. Compared with vancomycin and moxifloxacin, treatment with different concentrations of IG1 reduced the viability of organisms in a very similar manner and the reduction was not significant, which indicated that IG1 is a potentially strong anti-S. aureus agent. Finally, the antibacterial mechanism was analyzed, with flow cytometric analysis revealing that IG1 treatment resulted in a time-dependent decrease in the DNA content of S. aureus. Transmission electron microscopy (TEM) analysis showed that very few dividing cells could be found and the cell wall was damaged in the field of IG1-treated cells. These results indicate that IG1 is a potential new antibacterial agent against S. aureus, including MRSA. MDPI 2022-11-16 /pmc/articles/PMC9697348/ /pubmed/36431037 http://dx.doi.org/10.3390/life12111902 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Xin
Lin, Yueqiao
Gao, Qianqian
Huang, Shiliang
Zhang, Zihua
Li, Nan
Zong, Xin
Guo, Xuemin
IG1, a Mansonone F Analog, Exhibits Antibacterial Activity against Staphylococcus aureus by Potentially Impairing Cell Wall Synthesis and DNA Replication
title IG1, a Mansonone F Analog, Exhibits Antibacterial Activity against Staphylococcus aureus by Potentially Impairing Cell Wall Synthesis and DNA Replication
title_full IG1, a Mansonone F Analog, Exhibits Antibacterial Activity against Staphylococcus aureus by Potentially Impairing Cell Wall Synthesis and DNA Replication
title_fullStr IG1, a Mansonone F Analog, Exhibits Antibacterial Activity against Staphylococcus aureus by Potentially Impairing Cell Wall Synthesis and DNA Replication
title_full_unstemmed IG1, a Mansonone F Analog, Exhibits Antibacterial Activity against Staphylococcus aureus by Potentially Impairing Cell Wall Synthesis and DNA Replication
title_short IG1, a Mansonone F Analog, Exhibits Antibacterial Activity against Staphylococcus aureus by Potentially Impairing Cell Wall Synthesis and DNA Replication
title_sort ig1, a mansonone f analog, exhibits antibacterial activity against staphylococcus aureus by potentially impairing cell wall synthesis and dna replication
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697348/
https://www.ncbi.nlm.nih.gov/pubmed/36431037
http://dx.doi.org/10.3390/life12111902
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