- Title
- Impact of a Novel Anticoccidial Analogue on Systemic Staphylococcus aureus Infection in a Bioluminescent Mouse Model
- Creator
- Nguyen, Hang Thi; Venter, Henrietta; Woolford, Lucy; Young, Kelly; McCluskey, Adam; Garg, Sanjay; Page, Stephen W.; Trott, Darren J.; Ogunniyi, Abiodun D.
- Relation
- Antibiotics Vol. 11, Issue 1, no. 65
- Publisher Link
- http://dx.doi.org/10.3390/antibiotics11010065
- Publisher
- MDPI AG
- Resource Type
- journal article
- Date
- 2022
- Description
- 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 concentra-tion/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.
- Subject
- NCL179; colistin; robenidine; gram-positive bacteria; staphylococcus aureus; gram-negative bacteria
- Identifier
- http://hdl.handle.net/1959.13/1457828
- Identifier
- uon:45380
- Identifier
- ISSN:20796382
- 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/)
- Language
- eng
- Full Text
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