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

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 meda...

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Autores principales:	Miao Dong, Shu Hin Kwok, Joseph L. Humble, Yimin Liang, Sze Wing Tang, Kin Hung Tang, Man Kit Tse, Josh Haipeng Lei, Rajkumar Ramalingam, Mohamad Koohi-Moghadam, Doris Wai Ting Au, Hongyan Sun, Yun Wah Lam
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3e24d8701d7a449795ad52ee7284af08
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spelling	oai:doaj.org-article:3e24d8701d7a449795ad52ee7284af082021-12-02T17:30:34ZBING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expression10.1038/s41598-021-91765-42045-2322https://doaj.org/article/3e24d8701d7a449795ad52ee7284af082021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91765-4https://doaj.org/toc/2045-2322Abstract 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.Miao DongShu Hin KwokJoseph L. HumbleYimin LiangSze Wing TangKin Hung TangMan Kit TseJosh Haipeng LeiRajkumar RamalingamMohamad Koohi-MoghadamDoris Wai Ting AuHongyan SunYun Wah LamNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Miao Dong Shu Hin Kwok Joseph L. Humble Yimin Liang Sze Wing Tang Kin Hung Tang Man Kit Tse Josh Haipeng Lei Rajkumar Ramalingam Mohamad Koohi-Moghadam Doris Wai Ting Au Hongyan Sun Yun Wah Lam BING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expression
description	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.
format	article
author	Miao Dong Shu Hin Kwok Joseph L. Humble Yimin Liang Sze Wing Tang Kin Hung Tang Man Kit Tse Josh Haipeng Lei Rajkumar Ramalingam Mohamad Koohi-Moghadam Doris Wai Ting Au Hongyan Sun Yun Wah Lam
author_facet	Miao Dong Shu Hin Kwok Joseph L. Humble Yimin Liang Sze Wing Tang Kin Hung Tang Man Kit Tse Josh Haipeng Lei Rajkumar Ramalingam Mohamad Koohi-Moghadam Doris Wai Ting Au Hongyan Sun Yun Wah Lam
author_sort	Miao Dong
title	BING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expression
title_short	BING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expression
title_full	BING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expression
title_fullStr	BING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expression
title_full_unstemmed	BING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expression
title_sort	bing, a novel antimicrobial peptide isolated from japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxr expression
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3e24d8701d7a449795ad52ee7284af08
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BING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expression

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