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Rigshospitalet - en del af Københavns Universitetshospital
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The membrane-active polyaminoisoprenyl compound NV716 re-sensitizes Pseudomonas aeruginosa to antibiotics and reduces bacterial virulence

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  • Gang Wang
  • Jean-Michel Brunel
  • Matthias Preusse
  • Negar Mozaheb
  • Sven D Willger
  • Gerald Larrouy-Maumus
  • Pieter Baatsen
  • Susanne Häussler
  • Jean-Michel Bolla
  • Françoise Van Bambeke
Vis graf over relationer

Pseudomonas aeruginosa is intrinsically resistant to many antibiotics due to the impermeability of its outer membrane and to the constitutive expression of efflux pumps. Here, we show that the polyaminoisoprenyl compound NV716 at sub-MIC concentrations re-sensitizes P. aeruginosa to abandoned antibiotics by binding to the lipopolysaccharides (LPS) of the outer membrane, permeabilizing this membrane and increasing antibiotic accumulation inside the bacteria. It also prevents selection of resistance to antibiotics and increases their activity against biofilms. No stable resistance could be selected to NV716-itself after serial passages with subinhibitory concentrations, but the transcriptome of the resulting daughter cells shows an upregulation of genes involved in the synthesis of lipid A and LPS, and a downregulation of quorum sensing-related genes. Accordingly, NV716 also reduces motility, virulence factors production, and biofilm formation. NV716 shows a unique and highly promising profile of activity when used alone or in combination with antibiotics against P. aeruginosa, combining in a single molecule anti-virulence and potentiator effects. Additional work is required to more thoroughly understand the various functions of NV716.

OriginalsprogEngelsk
Artikelnummer871
TidsskriftCommunications biology
Vol/bind5
Udgave nummer1
Sider (fra-til)871
ISSN2399-3642
DOI
StatusUdgivet - 25 aug. 2022

Bibliografisk note

© 2022. The Author(s).

ID: 84183221