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Fish Shellfish Immunol. 2019 Jan;84:912-919. doi: 10.1016/j.fsi.2018.10.071. Epub 2018 Oct 30.

Phenylalanine enhances innate immune response to clear ceftazidime-resistant Vibrio alginolyticus in Danio rerio.

Author information

1
Center for Proteomics and Metabolomics, State Key Laboratory of Bio-Control, School of Life Sciences, Sun Yat-sen University, University City, Guangzhou, 510006, People's Republic of China.
2
Pediatric Intensive Care Unit, Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
3
Faculty of Health Sciences, University of Macau, Macau SAR, China.
4
Center for Proteomics and Metabolomics, State Key Laboratory of Bio-Control, School of Life Sciences, Sun Yat-sen University, University City, Guangzhou, 510006, People's Republic of China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266071, China. Electronic address: pengb26@mail.sysu.edu.cn.

Abstract

Antibiotic-resistant bacteria becomes a major threat to the economy and food safety in aquaculture. Although the antibiotic-dependent strategy is still the mostly adopted option, the development of antibiotic-free approach is urgently needed to ameliorate the severe situation of the global antibiotic resistance. In the present study, we showed that modulating the metabolism of zebrafish, Danio reiro, would enhance D. rerio to clear ceftazidime-resistant Vibrio alginoyticus (Caz-R) in vivo. By generating Caz-R in vitro, we found Caz-R stays longer than ceftazidime-sensitive V. alginoyticus (Caz-S) in D. rerio, where Caz-R induced less potent immune response than that of Caz-S. The differential immune response was associated with different metabolism of the host. Through functional metabolomics, we identified a crucial biomarker, phenylalanine. The abundance of phenylalanine was increased in both of Caz-S and Caz-R infected hosts but the abundance was higher in Caz-S infected group. This specific difference indicated phenylalanine could be a metabolite required to clear Caz-R by the host. Exogenous phenylalanine would enhance the host's ability to remove Caz-R, which was through upregulated production of lysozyme and C3b. Thus, our study demonstrates a novel strategy to boost host's immune response to combat against antibiotic-resistant bacteria.

KEYWORDS:

Ceftazidime resistance; Innate immune response; Metabolomics; Phenylalanine; Vibrio alginolyticus

PMID:
30389644
DOI:
10.1016/j.fsi.2018.10.071
[Indexed for MEDLINE]

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