(485bd) The Structural Effects On Biofilm Inhibition and Dispersion by Trp/Arg Antimicrobial Peptides

Biofilms
are sessile microbial communities that attach to a variety of surfaces. Due to
significantly enhanced tolerance to antibiotics, biofilms cause serious chronic
infections with high morbidity and mortality. In order to develop
more effective approaches for biofilm control, a series of linear cationic
antimicrobial peptides (AMPs) with varying tryptophan (Trp or W) and arginine
(Arg or R) repeats ([RW]_n-NH₂, where n = 2, 3, or 4), as
well as the dendrimeric peptide [RW]_4D were rigorously compared to correlate
their structures with antimicrobial activities on the planktonic growth and biofilm
formation of Escherichia coli.

The
antimicrobial activities of peptides against planktonic growth were found to
increase significantly with the size of peptide molecules; e.g., the dendrimer exhibited
almost complete growth inhibition at 25 µM. In addition, all AMPs except tetramer
significantly reduced E. coli biofilm surface coverage and viability of
biofilm cells when added at inoculation. Among the peptides tested, dendrimer
exhibited the strongest activity; e.g., E. coli biofilm formation was
reduced by 89.2 ± 3.1% by 25 μM dendrimer based on surface coverage compared
to peptide-free control. These results are corroborated by the finding that E.
coli motility was significantly reduced by hexamer, octamer, and dendrimer
at 25 μM.

In
addition to biofilm prevention, significant killing of biofilm cells was
observed after a 3-h treatment of mature biofilms by hexamer and dendrimer. Interestingly,
treatment with octamer caused significant biofilm dispersion without apparent
killing of biofilm cells; e.g., the biofilms were removed by 47.4 ± 6.2%, 71.5
± 9.2%, 87.9 ± 8.0%, and 91.5 ± 3.5% by 25, 50, 100, and 200 μM octamer,
respectively. Overall, these results suggest that hexamer, octamer, and dendrimer
are potent inhibitors of both planktonic growth and biofilm formation, while
octamer can also disperse mature biofilms. The possible mechanisms will be
discussed to explain these observations. These results are helpful for
designing novel biofilm inhibitors and developing more effective therapeutic methods.