posted on 2021-09-20, 15:07authored byTharwat Mohy El
Dine, Ravikumar Jimmidi, Andrei Diaconu, Maude Fransolet, Carine Michiels, Julien De Winter, Emilie Gillon, Anne Imberty, Tom Coenye, Stéphane P. Vincent
Pseudomonas aeruginosa (P.A.) is
a human pathogen belonging to the top priorities for the discovery
of new therapeutic solutions. Its propensity to generate biofilms
strongly complicates the treatments required to cure P.A. infections.
Herein, we describe the synthesis of a series of novel rotaxanes composed
of a central galactosylated pillar[5]arene, a tetrafucosylated dendron,
and a tetraguanidinium subunit. Besides the high affinity of the final
glycorotaxanes for the two P.A. lectins LecA and LecB, potent inhibition
levels of biofilm growth were evidenced, showing that their three
subunits work synergistically. An antibiofilm assay using a double
ΔlecAΔlecB mutant compared
to the wild type demonstrated that the antibiofilm activity of the
best glycorotaxane is lectin-mediated. Such antibiofilm potency had
rarely been reached in the literature. Importantly, none of the final
rotaxanes was bactericidal, showing that their antibiofilm activity
does not depend on bacteria killing, which is a rare feature for antibiofilm
agents.