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Potent antibacterial and antibiofilm activities of TICbf-14, a peptide with increased stability against trypsin

  • Microbial Pathogenesis and Host-Microbe Interaction
  • Published:
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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.

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Acknowledgements

This work was funded by the National Key Research and Development ProGram of China (2018YFA0902000); National Natural Science Foundation of China (No.82173863; No.81803591); the fellowship of china postdoctoral science foundation (2020T130723); Natural Science Foundation of Jiangsu Province of China (No. BK20180563; No. BK2020-1327); the Basic Scientific Research Business Expense Project of China Pharmaceutical University (No. 2632021ZD07). Youth Science and Technology Talent Support Project of Jiangsu Association for Science and Technology (tj1288).

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Authors and Affiliations

  1. School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, 211198, P. R. China

    Liping Wang, Xiaoyun Liu, Xinyue Ye, Chenyu Zhou, Wenxuan Zhao, Changlin Zhou & Lingman Ma

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  1. Liping Wang
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  2. Xiaoyun Liu
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  3. Xinyue Ye
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  4. Chenyu Zhou
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  5. Wenxuan Zhao
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  6. Changlin Zhou
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  7. Lingman Ma
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Contributions

Changlin Zhou and Lingman Ma designed research; Liping Wang performed the experiments and edited the manuscript; Xiaoyun Liu, Xinyue Ye, Chenyu Zhou, Wenxuan Zhao contributed new methods; Changlin Zhou and Lingman Ma provided funding sources. All authors read and approved the manuscript.

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Correspondence to Changlin Zhou or Lingman Ma.

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All authors declare that they have no conflicts of interest.

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Wang, L., Liu, X., Ye, X. et al. Potent antibacterial and antibiofilm activities of TICbf-14, a peptide with increased stability against trypsin. J Microbiol. 60, 89–99 (2022). https://doi.org/10.1007/s12275-022-1368-9

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  • DOI: https://doi.org/10.1007/s12275-022-1368-9

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