BING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expression

Dong, M. et al. (2021) BING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expression. Scientific Reports, 11, 12219. (doi: 10.1038/s41598-021-91765-4) (PMID:34108601) (PMCID:PMC8190156)

Abstract

Antimicrobial peptides (AMPs) have emerged as a promising alternative to small molecule antibiotics. Although AMPs have previously been isolated in many organisms, efforts on the systematic identification of AMPs in fish have been lagging. Here, we collected peptides from the plasma of medaka (Oryzias latipes) fish. By using mass spectrometry, 6399 unique sequences were identified from the isolated peptides, among which 430 peptides were bioinformatically predicted to be potential AMPs. One of them, a thermostable 13-residue peptide named BING, shows a broad-spectrum toxicity against pathogenic bacteria including drug-resistant strains, at concentrations that presented relatively low toxicity to mammalian cell lines and medaka. Proteomic analysis indicated that BING treatment induced a deregulation of periplasmic peptidyl-prolyl isomerases in gram-negative bacteria. We observed that BING reduced the RNA level of cpxR, an upstream regulator of envelope stress responses. cpxR is known to play a crucial role in the development of antimicrobial resistance, including the regulation of genes involved in drug efflux. BING downregulated the expression of efflux pump components mexB, mexY and oprM in P. aeruginosa and significantly synergised the toxicity of antibiotics towards these bacteria. In addition, exposure to sublethal doses of BING delayed the development of antibiotic resistance. To our knowledge, BING is the first AMP shown to suppress cpxR expression in Gram-negative bacteria. This discovery highlights the cpxR pathway as a potential antimicrobial target.

• Item Type: Articles
• Additional Information: This work was supported by the Health and Medical Research Fund (HMRF, project number 18170572), Department of Health, Hong Kong, and City University of Hong Kong Applied Research Grant (ARG, project number 9667178), City University of Hong Kong, Hong Kong.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Humble, Joseph
• Authors: Dong, M., Kwok, S. H., Humble, J. L., Liang, Y., Tang, S. W., Tang, K. H., Tse, M. K., Lei, J. H., Ramalingam, R., Koohi-Moghadam, M., Au, D. W. T., Sun, H., and Lam, Y. W.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Scientific Reports
• Publisher: Nature Research
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Scientific Reports 11: 12219
• Publisher Policy: Reproduced under a Creative Commons License