Title |
Potent antibacterial and antibiofilm activities of TICbf-14, a peptide with increased stability against trypsin |
Author |
Liping Wang, Xiaoyun Liu, Xinyue Ye, Chenyu Zhou, Wenxuan Zhao, Changlin Zhou*, and Lingman Ma* |
Address |
School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 211198, P. R. China |
Bibliography |
Journal of Microbiology, 60(1),89-99, 2022,
|
DOI |
10.1007/s12275-022-1368-9
|
Key Words |
TICbf-14, trypsin inhibition, antimicrobial activity,
biofilm inhibition, ionic bridge, membrane-disruptive mode |
Abstract |
The poor stability of peptides against trypsin largely limits
their development as potential antibacterial agents. Here, to
obtain a peptide with increased trypsin stability and potent
antibacterial activity, TICbf-14 derived from the cationic peptide
Cbf-14 was designed by the addition of disulfide-bridged
hendecapeptide (CWTKSIPPKPC) loop. Subsequently, the
trypsin stability and antimicrobial and antibiofilm activities
of this peptide were evaluated. The possible mechanisms underlying
its mode of action were also clarified. The results
showed that TICbf-14 exhibited elevated trypsin inhibitory
activity and effectively mitigated lung histopathological damage
in bacteria-infected mice by reducing the bacterial counts,
further inhibiting the systemic dissemination of bacteria and
host inflammation. Additionally, TICbf-14 significantly repressed
bacterial swimming motility and notably inhibited
biofilm formation. Considering the mode of action, we observed
that TICbf-14 exhibited a potent membrane-disruptive
mechanism, which was attributable to its destructive effect
on ionic bridges between divalent cations and LPS of the bacterial
membrane. Overall, TICbf-14, a bifunctional peptide
with both antimicrobial and trypsin inhibitory activity, is
highly likely to become an ideal candidate for drug development
against bacteria. |