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The N-terminal and central domain of colicin A enables phage lysin to lyse Escherichia coli extracellularly

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Abstract

Multidrug-resistant Escherichia coli has seriously threatened antibiotic resources and international public health. Bacteriophage lysin preparations have been widely considered as valid agents for solving multidrug resistances. Many lysins have been derived to treat diseases caused by Gram-positive bacteria, but only a few lysin preparations have been found that successively treat diseases caused by Gram-negative bacteria. The outer membrane of Gram-negative bacteria effectively blocks the interactions between peptidoglycan in the periplasmic space and bacteriophage lysins, which therefore hampers the antimicrobial effects of bacteriophage lysins. In this study, a new fusion protein (Colicin-Lysep3) was constructed by fusing the translocation and receptor binding domains of colicin A with an E. coli phage lysin, which endows Colicin-Lysep3 bactericidal activity against E. coli from outside of Gram-negative bacteria. These results show that Colicin-Lysep3 could lyse the E. coli broadly in vitro and significantly reduce the number of E. coli in an intestinal infection mouse model. Overall, our findings first demonstrated that a colicin A fragment could enable a bacteriophage lysin to lyse E. coli from the outside, promoting the application of phage lysin preparations in control of Gram-negative bacteria.

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Funding

The study was supported by funds from the National Key Basic Research Program of China (No. 2013CB127205).

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Author notes

  1. Junling Yang & Liancheng Lei

    Present address: College of Veterinary Medicine, Jilin University, Xi’an Road 5333, Changchun, 130062, Jilin, People’s Republic of China

  2. Junling Yang, who contributed equally with Liancheng Lei to the experiments, is co-corresponding author.

Authors and Affiliations

  1. College of Veterinary Medicine, Jilin University, Xi’an Road 5333, Changchun, 130062, Jilin, People’s Republic of China

    Guangmou Yan, Jianfang Liu, Qiang Ma, Rining Zhu, Chencheng Gao, Shuang Wang, Ling Yu, Jingmin Gu, Dongliang Hu, Wenyu Han & Liancheng Lei

  2. Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, People’s Republic of China

    Zhimin Guo & Junling Yang

  3. Department of Zoonoses, Kitasato University School of Veterinary Medicine, Aomori, Japan

    Dongliang Hu

  4. College of Chinese Medicine Material, Jilin Agricultural University, Changchun, 130118, China

    Rui Du

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  1. Guangmou Yan
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Correspondence to Liancheng Lei.

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The authors declare that they have no competing interests.

Ethical approval

Mice were purchased from the Animal Experiment Center of Jilin University. All animal research was conducted according to the experimental practices and standards approved by the Animal Welfare and Research Committee at Jilin University (Approval ID: 20100926-1).

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Yan, G., Liu, J., Ma, Q. et al. The N-terminal and central domain of colicin A enables phage lysin to lyse Escherichia coli extracellularly. Antonie van Leeuwenhoek 110, 1627–1635 (2017). https://doi.org/10.1007/s10482-017-0912-9

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  • DOI: https://doi.org/10.1007/s10482-017-0912-9

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