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Issue 27, 2019
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A thiochromenone antibiotic derived from the Pseudomonas quinolone signal selectively targets the Gram-negative pathogen Moraxella catarrhalis

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Abstract

The Pseudomonas quinolone signal (PQS) is an important quorum sensing signal of the pathogen Pseudomonas aeruginosa. We discovered an additional activity of PQS as a narrow spectrum antibiotic. Exploiting the privileged structure of PQS by the synthesis of heteroatom-substituted analogues led to a class of 2-alkyl-3-hydroxythiochromen-4-ones with highly potent antibiotic activity against the nasopharyngeal pathogen Moraxella catarrhalis. Synthetic optimization resulted in minimum inhibitory concentrations in the nanomolar range even for clinical isolates of M. catarrhalis. Surprisingly, the growth of other human pathogens and commensals, including closely related Moraxella species, was not inhibited, indicating exceptional species selectivity. Mechanistic studies revealed that the antibiotic was bactericidal and likely inhibits a target in the primary energy metabolism causing rapid depletion of the cellular ATP pool.

Graphical abstract: A thiochromenone antibiotic derived from the Pseudomonas quinolone signal selectively targets the Gram-negative pathogen Moraxella catarrhalis

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Article information


Submitted
04 Mar 2019
Accepted
23 May 2019
First published
23 May 2019

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2019,10, 6624-6628
Article type
Edge Article

A thiochromenone antibiotic derived from the Pseudomonas quinolone signal selectively targets the Gram-negative pathogen Moraxella catarrhalis

D. Szamosvári, T. Schuhmacher, C. R. Hauck and T. Böttcher, Chem. Sci., 2019, 10, 6624
DOI: 10.1039/C9SC01090D

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