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Identification of a lytic Pseudomonas aeruginosa phage depolymerase and its anti-biofilm effect and bactericidal contribution to serum

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Abstract

Pseudomonas aeruginosa (P. aeruginosa) infection has imposed a great threat to patients with cystic fibrosis. With the emergence of multidrug-resistant P. aeruginosa, developing an alternative anti-microbial strategy is indispensable and more urgent than ever. In this study, a lytic P. aeruginosa phage was isolated from the sewage of a hospital, and one protein was predicted as the depolymerase-like protein by genomic sequence analysis, it includes two catalytic regions, the Pectate lyase_3 super family and Glycosyl hydrolase_28 super family. Further analysis demonstrated that recombinant depolymerase-like protein degraded P. aeruginosa exopolysaccharide and enhanced bactericidal activity mediated by serum in vitro. Additionally, this protein disrupted host bacterial biofilms. All of these results showed that the phage-derived depolymerase-like protein has the potential to be developed into an anti-microbial agent that targets P. aeruginosa.

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Funding

This study was supported by the National Natural Science Foundation of China (81572045), the Capital Characteristic Clinic Project of Beijing (Z121107001012127), the Beijing Natural Science Foundation (7142118), and the National Key Research and Development Program of China (2017YFF0108605).

Author information

Author notes

  1. Liyuan Mi and Yannan Liu have contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Marine Drugs, Chinese Ministry of Education; Key Laboratory of Glycoscience & Glycotechnology of Shandong Province; School of Medicine and Pharmacy; Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China

    Liyuan Mi, Shan Gao, Wengong Yu & Feng Han

  2. Department of Respiratory and Critical Care Medicine, 307th Hospital of PLA, No. 8 Dongda Street, Fengtai District, Beijing, 100071, China

    Yannan Liu, Can Wang & Changqing Bai

  3. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China

    Tongtong He, Shaozhen Xing, Yong Huang, Hang Fan, Xianglilan Zhang, Zhiqiang Mi & Yigang Tong

  4. Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, China

    Yannan Liu

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  1. Liyuan Mi
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Contributions

MLY conducted the identification, expression, and evaluation of the depolymerase and drafted the manuscript. LYN screened and identified the Pa.1193 bacterium. WC performed the exopolysaccharide extraction and staining. GS performed the bacterial biofilm experiment. HTT isolated the IME180 phage. XSZ conducted the depolymerase purification. HY, FH, and ZXLL performed genomic analyses and annotation. TYG, YWG, and MZQ revised the manuscript. BCQ and HF conceived and designed the experiments. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Changqing Bai or Feng Han.

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All procedures involving animals were in accordance with ethical standards.

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Edited by Detlev H. Kruger.

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Mi, L., Liu, Y., Wang, C. et al. Identification of a lytic Pseudomonas aeruginosa phage depolymerase and its anti-biofilm effect and bactericidal contribution to serum. Virus Genes 55, 394–405 (2019). https://doi.org/10.1007/s11262-019-01660-4

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  • DOI: https://doi.org/10.1007/s11262-019-01660-4

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