1. Front Microbiol. 2017 Dec 22;8:2585. doi: 10.3389/fmicb.2017.02585. eCollection

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(1)(2), Verstraete L(1)(2), Van Bambeke F(3), Anantharajah A(3),
Townsend EM(4)(5), Ramage G(4), Corbau R(6), Marchand A(6), Chaltin P(6)(7),
Fauvart M(1)(8), Michiels J(1)(2).

Author information: 
(1)Centre of Microbial and Plant Genetics, University of Leuven, Leuven, Belgium.
(2)Center for Microbiology, Vlaams Instituut voor Biotechnologie, Leuven,
(3)Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute,
Université catholique de Louvain, Brussels, Belgium.
(4)Oral Science Research Group, Glasgow Dental School, University of Glasgow,
Glasgow, United Kingdom.
(5)Institute of Healthcare Policy and Practice, University of West of Scotland,
Paisley, United Kingdom.
(6)CISTIM Leuven vzw, Leuven, Belgium.
(7)Centre for Drug Design and Discovery, Leuven, Belgium.
(8)Department of Life Sciences and Imaging, Smart Electronics Unit, imec, Leuven,

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.

DOI: 10.3389/fmicb.2017.02585 
PMCID: PMC5744096
PMID: 29312259