1-((2,4-Dichlorophenethyl)Amino)-3-Phenoxypropan-2-ol Kills Pseudomonas aeruginosa through Extensive Membrane Damage

Frontiers in Microbiology
Valerie DefraineJan Michiels

Abstract

The ever increasing multidrug-resistance of clinically important pathogens and the lack of novel antibiotics have resulted in a true antibiotic crisis where many antibiotics are no longer effective. Further complicating the treatment of bacterial infections are antibiotic-tolerant persister cells. Besides being responsible for the recalcitrant nature of chronic infections, persister cells greatly contribute to the observed antibiotic tolerance in biofilms and even facilitate the emergence of antibiotic resistance. Evidently, eradication of these persister cells could greatly improve patient outcomes and targeting persistence may provide an alternative approach in combatting chronic infections. We recently characterized 1-((2,4-dichlorophenethyl)amino)-3-phenoxypropan-2-ol (SPI009), a novel anti-persister molecule capable of directly killing persisters from both Gram-negative and Gram-positive pathogens. SPI009 potentiates antibiotic activity in several in vitro and in vivo infection models and possesses promising anti-biofilm activity. Strikingly, SPI009 restores antibiotic sensitivity even in resistant strains. In this study, we investigated the mode of action of this novel compound using several parallel approaches. Genetic a...Continue Reading

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Citations

Nov 14, 2018·International Journal of Antimicrobial Agents·Marion NicolEmmanuelle Dé
Aug 31, 2021·RSC Medicinal Chemistry·Cassandra L SchrankWilliam M Wuest

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Methods Mentioned

BETA
Whole Genome Sequencing
PCR
gene knockout

Software Mentioned

Bowtie2
PseudoCAP
FastQC
PheNetic
DESeq2
CLC Genomics Workbench
Cytoscape

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