Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/134340
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Type: | Journal article |
Title: | Impact of a novel anticoccidial analogue on systemic staphylococcus aureus infection in a bioluminescent mouse model |
Author: | Nguyen, H.T. Venter, H. Woolford, L. Young, K. McCluskey, A. Garg, S. Page, S.W. Trott, D.J. Ogunniyi, A.D. |
Citation: | Antibiotics, 2022; 11(1):1-16 |
Publisher: | MDPI |
Issue Date: | 2022 |
ISSN: | 2079-6382 2079-6382 |
Statement of Responsibility: | Hang Thi Nguyen, Henrietta Venter, Lucy Woolford, Kelly Young, Adam McCluskey, Sanjay Garg ... et al. |
Abstract: | In this study, we investigated the potential of an analogue of robenidine (NCL179) to expand its chemical diversity for the treatment of multidrug-resistant (MDR) bacterial infections. We show that NCL179 exhibits potent bactericidal activity, returning minimum inhibitory concentration/minimum bactericidal concentrations (MICs/MBCs) of 1–2 µg/mL against methicillin-resistant Staphylococcus aureus, MICs/MBCs of 1–2 µg/mL against methicillin-resistant S. pseudintermedius and MICs/MBCs of 2–4 µg/mL against vancomycin-resistant enterococci. NCL179 showed synergistic activity against clinical isolates and reference strains of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa in the presence of sub-inhibitory concentrations of colistin, whereas NCL179 alone had no activity. Mice given oral NCL179 at 10 mg/kg and 50 mg/kg (4 × doses, 4 h apart) showed no adverse clinical effects and no observable histological effects in any of the organs examined. In a bioluminescent S. aureus sepsis challenge model, mice that received four oral doses of NCL179 at 50 mg/kg at 4 h intervals exhibited significantly reduced bacterial loads, longer survival times and higher overall survival rates than the vehicle-only treated mice. These results support NCL179 as a valid candidate for further development to treat MDR bacterial infections as a stand-alone antibiotic or in combination with existing antibiotic classes. |
Keywords: | NCL179; colistin; robenidine; Gram-positive bacteria; Staphylococcus aureus; Gram-negative bacteria; multidrug-resistance; bioluminescence; antibiotic combination |
Rights: | © 2022 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 (https:// creativecommons.org/licenses/by/ 4.0/). |
DOI: | 10.3390/antibiotics11010065 |
Grant ID: | http://purl.org/au-research/grants/arc/LP110200770 |
Published version: | http://dx.doi.org/10.3390/antibiotics11010065 |
Appears in Collections: | Animal and Veterinary Sciences publications |
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hdl_134340.pdf | Published version | 3.56 MB | Adobe PDF | View/Open |
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