Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Tan, Xinyi, Xie, Haoji, Zhang, Bin, Zhou, Jiale, Dou, Zhende, Wang, Xiao, Wang, Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1783659065992282112
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
work_keys_str_mv AT tanxinyi anovelivermectinderivedcompoundd4anditsantimicrobialbiofilmpropertiesagainstmrsa
AT xiehaoji anovelivermectinderivedcompoundd4anditsantimicrobialbiofilmpropertiesagainstmrsa
AT zhangbin anovelivermectinderivedcompoundd4anditsantimicrobialbiofilmpropertiesagainstmrsa
AT zhoujiale anovelivermectinderivedcompoundd4anditsantimicrobialbiofilmpropertiesagainstmrsa
AT douzhende anovelivermectinderivedcompoundd4anditsantimicrobialbiofilmpropertiesagainstmrsa
AT wangxiao anovelivermectinderivedcompoundd4anditsantimicrobialbiofilmpropertiesagainstmrsa
AT wangning anovelivermectinderivedcompoundd4anditsantimicrobialbiofilmpropertiesagainstmrsa
AT tanxinyi novelivermectinderivedcompoundd4anditsantimicrobialbiofilmpropertiesagainstmrsa
AT xiehaoji novelivermectinderivedcompoundd4anditsantimicrobialbiofilmpropertiesagainstmrsa
AT zhangbin novelivermectinderivedcompoundd4anditsantimicrobialbiofilmpropertiesagainstmrsa
AT zhoujiale novelivermectinderivedcompoundd4anditsantimicrobialbiofilmpropertiesagainstmrsa
AT douzhende novelivermectinderivedcompoundd4anditsantimicrobialbiofilmpropertiesagainstmrsa
AT wangxiao novelivermectinderivedcompoundd4anditsantimicrobialbiofilmpropertiesagainstmrsa
AT wangning novelivermectinderivedcompoundd4anditsantimicrobialbiofilmpropertiesagainstmrsa