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Peptide dendrimers G3KL and TNS18 inhibit Pseudomonas aeruginosa biofilms

  • Xiao Han
  • Yujie Liu
  • Yibing Ma
  • Mengqing Zhang
  • Zhengjin He
  • Thissa N. Siriwardena
  • Haijin Xu
  • Yanling Bai
  • Xiuming Zhang
  • Jean-Louis ReymondEmail author
  • Mingqiang QiaoEmail author
Applied microbial and cell physiology

Abstract

Herein we report that peptide dendrimers G3KL and TNS18, which were recently reported to control multidrug-resistant bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, strongly inhibit biofilm formation by P. aeruginosa PA14 below their minimum inhibitory concentration (MIC) value, under which conditions they also strongly affect swarming motility. Eradication of preformed biofilms, however, required concentrations above the MIC values. Scanning electron microscopy observation and confocal laser scanning micrographs showed that peptide dendrimers can destroy the biofilm morphological structure and thickness in a dose-dependent manner, even make the biofilm dispersed completely. Membrane potential analysis indicated that planktonic cells treated with peptide dendrimers presented an increase in fluorescence intensity, suggesting that cytoplasmic membrane could be the target of G3KL and TNS18 similarly to polymyxin B. RNA-seq analysis showed that the expressions of genes in the arnBCADTEF operon-regulating lipid A modification resulting in resistance to AMPs are differentially affected between these three compounds, suggesting that each compound targets the cell membrane but in different manner. Potent activity on planktonic cells and biofilms of P. aeruginosa suggests that peptide dendrimers G3KL and TNS18 are promising candidates of clinical development for treating infections.

Keywords

Pseudomonas aeruginosa Biofilm Peptide dendrimers Membrane Polymyxin B Mingqiang Qiao and Jean-Louis Reymond contributed equally to this work. 

Notes

Acknowledgments

The authors greatly appreciate Prof. Dr. Jean-Louis Reymond from Department of Chemistry and Biochemistry of the University of Bern (Switzerland) for providing the peptides G3KL and TNS18.

Funding

This work was supported in part by the Sino-Swiss scientific and technological cooperation project supported by the Ministry of Science and Technology of China (No. 2015DFG32140), the National Natural Science Foundation of China (No. 31770102), and the Swiss National Science Foundation (No. IZLCZ2_155982).

Compliance with ethical standards

This article does not contain any study with human participants or animals performed by any of the authors.

Conflict of interest

The authors declare they have no conflict of interest.

Supplementary material

253_2019_9801_MOESM1_ESM.pdf (412 kb)
ESM 1 (PDF 423 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Xiao Han
    • 1
  • Yujie Liu
    • 1
  • Yibing Ma
    • 1
  • Mengqing Zhang
    • 2
  • Zhengjin He
    • 3
  • Thissa N. Siriwardena
    • 4
  • Haijin Xu
    • 1
  • Yanling Bai
    • 1
  • Xiuming Zhang
    • 1
  • Jean-Louis Reymond
    • 4
    Email author
  • Mingqiang Qiao
    • 1
    Email author
  1. 1.The Key Laboratory of Molecular Microbiology and Technology Ministry of EducationNankai UniversityTianjinChina
  2. 2.Electricity Information and Automation CollegeCivil Aviation University of ChinaTianjinChina
  3. 3.Key Laboratory of Systems Biology, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina
  4. 4.Department of Chemistry and BiochemistryUniversity of BernBernSwitzerland

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