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A Novel Ivermectin-Derived Compound D4 and Its Antimicrobial/Biofilm Properties against MRSA
Methicillin-resistant Staphylococcus aureus (MRSA) and its biofilms infection is still a serious threat to global health. It is urgent to develop efficient drugs by repositioning or designing drugs to solve this problem. In this study, the antibacterial/biofilm activity and mechanisms of ivermectin...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924331/ https://www.ncbi.nlm.nih.gov/pubmed/33672669 http://dx.doi.org/10.3390/antibiotics10020208 |
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author | Tan, Xinyi Xie, Haoji Zhang, Bin Zhou, Jiale Dou, Zhende Wang, Xiao Wang, Ning |
author_facet | Tan, Xinyi Xie, Haoji Zhang, Bin Zhou, Jiale Dou, Zhende Wang, Xiao Wang, Ning |
author_sort | Tan, Xinyi |
collection | PubMed |
description | Methicillin-resistant Staphylococcus aureus (MRSA) and its biofilms infection is still a serious threat to global health. It is urgent to develop efficient drugs by repositioning or designing drugs to solve this problem. In this study, the antibacterial/biofilm activity and mechanisms of ivermectin (D) and its 4″-position amino substitution derivative (D4) against MRSA were investigated. The minimum inhibitory concentration (MIC) of D was 20 μg/mL, which is four times higher than D4 (MIC = 5 μg/mL). The mechanism research demonstrated that D4 was more potent than D at destroying bacterial cell wall, permeating cell membrane (6.25–36.0% vs 1.92–6.04%) and binding to MRSA genomic DNA. Moreover, after incubation with 10–40 μg/mL D4 for 24 h, the percentages of biofilm decreased by 21.2–92.9%, which was more effective than D (no significant change at 40 μg/mL). The antibiofilm effect is achieved by regulating the expression of related genes (RSH, relQ, rsbU, sigB, spA, and icaD). Additionally, though the higher hemolysis makes D4 a safety risk for intravenous injection, other administration options could be considered as well. Therefore, all the results have indicated that D4 may be a potential candidate compound for the treatment of MRSA and its biofilm infections. |
format | Online Article Text |
id | pubmed-7924331 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79243312021-03-03 A Novel Ivermectin-Derived Compound D4 and Its Antimicrobial/Biofilm Properties against MRSA Tan, Xinyi Xie, Haoji Zhang, Bin Zhou, Jiale Dou, Zhende Wang, Xiao Wang, Ning Antibiotics (Basel) Article Methicillin-resistant Staphylococcus aureus (MRSA) and its biofilms infection is still a serious threat to global health. It is urgent to develop efficient drugs by repositioning or designing drugs to solve this problem. In this study, the antibacterial/biofilm activity and mechanisms of ivermectin (D) and its 4″-position amino substitution derivative (D4) against MRSA were investigated. The minimum inhibitory concentration (MIC) of D was 20 μg/mL, which is four times higher than D4 (MIC = 5 μg/mL). The mechanism research demonstrated that D4 was more potent than D at destroying bacterial cell wall, permeating cell membrane (6.25–36.0% vs 1.92–6.04%) and binding to MRSA genomic DNA. Moreover, after incubation with 10–40 μg/mL D4 for 24 h, the percentages of biofilm decreased by 21.2–92.9%, which was more effective than D (no significant change at 40 μg/mL). The antibiofilm effect is achieved by regulating the expression of related genes (RSH, relQ, rsbU, sigB, spA, and icaD). Additionally, though the higher hemolysis makes D4 a safety risk for intravenous injection, other administration options could be considered as well. Therefore, all the results have indicated that D4 may be a potential candidate compound for the treatment of MRSA and its biofilm infections. MDPI 2021-02-20 /pmc/articles/PMC7924331/ /pubmed/33672669 http://dx.doi.org/10.3390/antibiotics10020208 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tan, Xinyi Xie, Haoji Zhang, Bin Zhou, Jiale Dou, Zhende Wang, Xiao Wang, Ning A Novel Ivermectin-Derived Compound D4 and Its Antimicrobial/Biofilm Properties against MRSA |
title | A Novel Ivermectin-Derived Compound D4 and Its Antimicrobial/Biofilm Properties against MRSA |
title_full | A Novel Ivermectin-Derived Compound D4 and Its Antimicrobial/Biofilm Properties against MRSA |
title_fullStr | A Novel Ivermectin-Derived Compound D4 and Its Antimicrobial/Biofilm Properties against MRSA |
title_full_unstemmed | A Novel Ivermectin-Derived Compound D4 and Its Antimicrobial/Biofilm Properties against MRSA |
title_short | A Novel Ivermectin-Derived Compound D4 and Its Antimicrobial/Biofilm Properties against MRSA |
title_sort | novel ivermectin-derived compound d4 and its antimicrobial/biofilm properties against mrsa |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924331/ https://www.ncbi.nlm.nih.gov/pubmed/33672669 http://dx.doi.org/10.3390/antibiotics10020208 |
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