Abstract :
[en] Many Pseudomonas spp. produce cyclic lipodepsipeptides (CLPs), which, besides their role in biological functions
such as motility, biofilm formation and interspecies interactions, are antimicrobial. It has been established that
interaction with the cellular membrane is central to the mode of action of CLPs. In this work, we focus on the
CLPs of the so-called viscosin group, aiming to assess the impact of the main structural variations observed within
this group on both the antimicrobial activity and the interaction with model membranes. The antimicrobial activity
of viscosin, viscosinamide A, WLIP and pseudodesmin A were all tested on a broad panel of mainly
Gram-positive bacteria. Their capacity to permeabilize or fuse PG/PE/cardiolipin model membrane vesicles is
assessed using fluorescent probes. We find that the Glu2/Gln2 structural variation within the viscosin group is
the main factor that influences both the membrane permeabilization properties and the minimum inhibitory
concentration of bacterial growth, while the configuration of the Leu5 residue has no apparent effect. The CLPmembrane
interactions were further evaluated using CD and FT-IR spectroscopy on model membranes consisting
of PG/PE/cardiolipin or POPC with or without cholesterol. In contrast to previous studies, we observe no conformational
change upon membrane insertion. The CLPs interact both with the polar heads and aliphatic tails of
model membrane systems, altering bilayer fluidity, while cholesterol reduces CLP insertion depth
Scopus citations®
without self-citations
19