Antibacterial activity of 1-[(2,4-dichlorophenethyl)amino]-3-phenoxypropan-2-ol against antibiotic-resistant strains of diverse bacterial pathogens, biofilms and in pre-clinical infection models

Defraine, V. et al. (2017) Antibacterial activity of 1-[(2,4-dichlorophenethyl)amino]-3-phenoxypropan-2-ol against antibiotic-resistant strains of diverse bacterial pathogens, biofilms and in pre-clinical infection models. Frontiers in Microbiology, 8, 2585. (doi:10.3389/fmicb.2017.02585) (PMID:29312259) (PMCID:PMC5744096)

Defraine, V. et al. (2017) Antibacterial activity of 1-[(2,4-dichlorophenethyl)amino]-3-phenoxypropan-2-ol against antibiotic-resistant strains of diverse bacterial pathogens, biofilms and in pre-clinical infection models. Frontiers in Microbiology, 8, 2585. (doi:10.3389/fmicb.2017.02585) (PMID:29312259) (PMCID:PMC5744096)

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Abstract

We recently described the novel anti-persister compound 1-[(2,4-dichlorophenethyl)amino]-3-phenoxypropan-2-ol (SPI009), capable of directly killing persister cells of the Gram-negative pathogen Pseudomonas aeruginosa. This compound also shows antibacterial effects against non-persister cells, suggesting that SPI009 could be used as an adjuvant for antibacterial combination therapy. Here, we demonstrate the broad-spectrum activity of SPI009, combined with different classes of antibiotics, against the clinically relevant ESKAPE pathogens Enterobacter aerogenes, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, P. aeruginosa, Enterococcus faecium and Burkholderia cenocepacia and Escherichia coli. Importantly, SPI009 re-enabled killing of antibiotic-resistant strains and effectively lowered the required antibiotic concentrations. The clinical potential was further confirmed in biofilm models of P. aeruginosa and S. aureus where SPI009 exhibited effective biofilm inhibition and eradication. Caenorhabditis elegans infected with P. aeruginosa also showed a significant improvement in survival when SPI009 was added to conventional antibiotic treatment. Overall, we demonstrate that SPI009, initially discovered as an anti-persister molecule in P. aeruginosa, possesses broad-spectrum activity and is highly suitable for the development of antibacterial combination therapies in the fight against chronic infections.

Item Type:Articles
Additional Information:This work was supported by Ph.D. grants of the Agency for Innovation through Science and Technology (IWT) to VD; the KU Leuven Excellence Center (grant number PF/2010/07), the KU Leuven Research Council (grant number PF/10/010, ‘NATAR’); the Belgian Science Policy Office (BELSPO) (IAP P7/28) and the Fund for Scientific Research, Flanders (FWO) (grant numbers G047112N; G0B2515N; G055517N).
Keywords:ESKAPE pathogens, P. aeruginosa, anti-persister therapies, antibacterials, antibiotic resistance.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ramage, Professor Gordon and Townsend, Miss Eleanor
Authors: Defraine, V., Verstraete, L., Van Bambeke, F., Anantharajah, A., Townsend, E. M., Ramage, G., Corbau, R., Marchand, A., Chaltin, P., Fauvart, M., and Michiels, J.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:Frontiers in Microbiology
Publisher:Frontiers
ISSN:1664-302X
ISSN (Online):1664-302X
Copyright Holders:Copyright © 2017 Defraine, Verstraete, Van Bambeke, Anantharajah, Townsend, Ramage, Corbau, Marchand, Chaltin, Fauvart and Michiels.
First Published:First published in Frontiers in Microbiology 8: 2585
Publisher Policy:Reproduced under a Creative Commons License

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