AUTHOR=Defraine Valerie , Verstraete Laure , Van Bambeke Françoise , Anantharajah Ahalieyah , Townsend Eleanor M. , Ramage Gordon , Corbau Romu , Marchand Arnaud , Chaltin Patrick , Fauvart Maarten , Michiels Jan 

TITLE=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

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.02585

DOI=10.3389/fmicb.2017.02585

ISSN=1664-302X

ABSTRACT=<p>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 <italic>Pseudomonas aeruginosa</italic>. 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 <italic>Enterobacter aerogenes, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, P. aeruginosa, Enterococcus faecium</italic> and <italic>Burkholderia cenocepacia</italic> and <italic>Escherichia coli</italic>. 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 <italic>P. aeruginosa</italic> and <italic>S. aureus</italic> where SPI009 exhibited effective biofilm inhibition and eradication. <italic>Caenorhabditis elegans</italic> infected with <italic>P. aeruginosa</italic> 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 <italic>P. aeruginosa</italic>, possesses broad-spectrum activity and is highly suitable for the development of antibacterial combination therapies in the fight against chronic infections.</p>