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

doi:10.3390/antibiotics10020208

Open AccessArticle

A Novel Ivermectin-Derived Compound D4 and Its Antimicrobial/Biofilm Properties against MRSA

by

Xinyi Tan

^1,†,

Haoji Xie

^1,†,

Bin Zhang

^2,†

,

Jiale Zhou

¹,

Zhende Dou

²,

Xiao Wang

^1,* and

Ning Wang

^3,*

¹

Immunology Innovation Team, School of medicine, Ningbo University, Ningbo 315211, Zhejiang, China

²

Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, Zhejiang, China

³

Institute of Drug Discovery Technology, Ningbo University, Ningbo 315211, Zhejiang, China

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Antibiotics 2021, 10(2), 208; https://doi.org/10.3390/antibiotics10020208

Submission received: 3 February 2021 / Revised: 17 February 2021 / Accepted: 18 February 2021 / Published: 20 February 2021

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Abstract

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.

Keywords: ivermectin derivative; MRSA; antibacterial; antibiofilm; mechanisms

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MDPI and ACS Style

Tan, X.; Xie, H.; Zhang, B.; Zhou, J.; Dou, Z.; Wang, X.; Wang, N. A Novel Ivermectin-Derived Compound D4 and Its Antimicrobial/Biofilm Properties against MRSA. Antibiotics 2021, 10, 208. https://doi.org/10.3390/antibiotics10020208

AMA Style

Tan X, Xie H, Zhang B, Zhou J, Dou Z, Wang X, Wang N. A Novel Ivermectin-Derived Compound D4 and Its Antimicrobial/Biofilm Properties against MRSA. Antibiotics. 2021; 10(2):208. https://doi.org/10.3390/antibiotics10020208

Chicago/Turabian Style

Tan, Xinyi, Haoji Xie, Bin Zhang, Jiale Zhou, Zhende Dou, Xiao Wang, and Ning Wang. 2021. "A Novel Ivermectin-Derived Compound D4 and Its Antimicrobial/Biofilm Properties against MRSA" Antibiotics 10, no. 2: 208. https://doi.org/10.3390/antibiotics10020208

APA Style

Tan, X., Xie, H., Zhang, B., Zhou, J., Dou, Z., Wang, X., & Wang, N. (2021). A Novel Ivermectin-Derived Compound D4 and Its Antimicrobial/Biofilm Properties against MRSA. Antibiotics, 10(2), 208. https://doi.org/10.3390/antibiotics10020208

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A Novel Ivermectin-Derived Compound D4 and Its Antimicrobial/Biofilm Properties against MRSA

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