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Resistance response to Arenicin derivatives in Escherichia coli

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Abstract

The rising prevalence of antibiotic resistance poses the greatest health threats. Antimicrobial peptides (AMPs) are regarded as the potentially effective therapy. To avoid current crisis of antibiotic resistance, a comprehensive understanding of AMP resistance is necessary before clinical application. In this study, the development of resistance to the anti-Gram-negative bacteria peptide N6NH2 (21 residues, β-sheet) was characterized in E. coli ATCC25922. Three N6NH2-resistant E. coli mutants with 32-fold increase in MIC were isolated by serially passaging bacterial lineages in progressively increasing concentrations of N6NH2 and we mainly focus on the phenotype of N6NH2-resistant bacteria different from sensitive bacteria. The results showed that the resistance mechanism was attributed to synergy effect of multiple mechanisms: (i) increase biofilm formation capacity (3 ~ 4-fold); (ii) weaken the affinity of lipopolysaccharide (LPS) with N6NH2 (3 ~ 8-fold); and (iii) change the cell membrane permeability and potential. Interestingly, a chimeric peptide-G6, also a N6NH2 analog, which keep the same antibacterial activity to both wild-type and resistant clones (MIC value: 16 μg/mL), could curb N6NH2-resistant mutants by stronger inhibition of biofilm formation, stronger affinity with LPS, and stronger membrane permeability and depolarization than that of N6NH2.

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All datasets generated for this study are included in the article/Supplementary material.

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Funding

This work was supported by the National Natural Science Foundation of China (grants No. 31772640, No. 31572444, and No. 31572445) and Direction of Antibiotic Peptides and Alternatives to Antibiotics, the Agricultural Science and Technology Innovation Program (CAAS-ASTIP-2013-FRI-02) and Key Project of Alternatives to Antibiotic for Feed Usages of ASTIP (CAAS-ZDXT2018008) in CAAS.

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Author notes

  1. Zhenlong Wang and Na Yang contributed equally to this work.

Authors and Affiliations

  1. Gene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, 12 Zhongguancun Nandajie St., Haidian District, Beijing, 100081, People’s Republic of China

    Zhenlong Wang, Na Yang, Da Teng, Ya Hao, Ting Li, Huihui Han, Ruoyu Mao & Jianhua Wang

  2. Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing, 100081, People’s Republic of China

    Zhenlong Wang, Na Yang, Da Teng, Ya Hao, Ting Li, Huihui Han, Ruoyu Mao & Jianhua Wang

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  1. Zhenlong Wang
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  2. Na Yang
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  3. Da Teng
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  4. Ya Hao
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  5. Ting Li
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  6. Huihui Han
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Contributions

Z.L.W., R.Y.M., and J.H.W. conceived and designed the experiments; Z.L.W. conducted the experiments; N.Y. and D.T. supervised the work; N.Y., D.T., Y.H., T.L., and H.H.H. provided some data analysis and revised the final version of the manuscript; Z.L.W., N.Y., R.Y.M., and J.H.W. wrote the manuscript.

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Correspondence to Ruoyu Mao or Jianhua Wang.

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Wang, Z., Yang, N., Teng, D. et al. Resistance response to Arenicin derivatives in Escherichia coli. Appl Microbiol Biotechnol 106, 211–226 (2022). https://doi.org/10.1007/s00253-021-11708-x

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  • DOI: https://doi.org/10.1007/s00253-021-11708-x

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