Escherichia coli Lipopolysaccharide Modulates Biological Activities of Human-β-Defensin Analogues but Not Non-Ribosomally Synthesized Peptides
2020
Human-β-defensins
(HBD1-3) are antibacterial peptides containing
three disulphide bonds. In the present study, the effect of Escherichia coli lipopolysaccharide (LPS) on the
antibacterial activities of HBD2-3, C-terminal analogues having a
single disulphide bond, Phd1-3, and their corresponding myristoylated
analogues MPhd1-3 were investigated. The effect of LPS on the activities
of linear amphipathic peptides melittin, LL37 and non-ribosomally
synthesized peptides, polymyxin B, alamethicin, gramicidin A, and
gramicidin S was also examined. The antibacterial activity of HBD
2-3, Phd1-3, and MPhd1-3 in the presence of LPS against E. coli and Staphylococcus aureus was inhibited. While LPS inhibited the antibacterial activity of
LL37, the inhibition of melittin activity was partial. The hemolytic
activity exhibited by MPhd1, MPhd3, melittin, and LL37 was inhibited
in the presence of LPS. HBD2-3, Phd1-3, and MPhd1-3 also showed endotoxin
neutralizing activity. The antibacterial and hemolytic activities
of polymyxin B, alamethicin, gramicidin A, and gramicidin S were not
inhibited in the presence of LPS. Fluorescence assays employing dansyl
cadaverine showed that HBD2-3 and defensin analogues bind to LPS more
strongly as compared to alamethicin, gramicidin A, and gramicidin
S. Electron microscopy images indicated that peptides disintegrate
the structure of LPS. The inhibition of the antibacterial activity
of native defensins and analogues in the presence of LPS indicates
that the initial interaction with the bacterial surface is similar.
The native defensin sequence or structure is also not essential, although
cationic charges are necessary for binding to LPS. Hydrophobic interaction
is the main driving force for association of non-ribosomally synthesized
polymyxin B, alamethicin, gramicidin A, and gramicidin S with LPS.
It is likely that these peptides rapidly insert into membranes and
do not interact with the bacterial cell surface, whereas cationic
peptides such as β-defensin and their analogues, melittin and
LL37, first interact with the bacterial cell surface and then the
membrane. Our results suggest that evaluating interaction of antibacterial
and hemolytic peptides with LPS is a compelling way of elucidating
the mechanism of bacterial killing or hemolysis.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
58
References
2
Citations
NaN
KQI