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...

Full description

Bibliographic Details
Main Authors:	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
Format:	Article
Language:	English
Published:	Nature Publishing Group 2021-06-01
Series:	Scientific Reports
Online Access:	https://doi.org/10.1038/s41598-021-91765-4

id	doaj-3e24d8701d7a449795ad52ee7284af08
record_format	Article
spelling	doaj-3e24d8701d7a449795ad52ee7284af082021-06-13T11:43:09ZengNature Publishing GroupScientific Reports2045-23222021-06-0111111710.1038/s41598-021-91765-4BING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expressionMiao Dong0Shu Hin Kwok1Joseph L. Humble2Yimin Liang3Sze Wing Tang4Kin Hung Tang5Man Kit Tse6Josh Haipeng Lei7Rajkumar Ramalingam8Mohamad Koohi-Moghadam9Doris Wai Ting Au10Hongyan Sun11Yun Wah Lam12Department of Chemistry, City University of Hong KongDepartment of Chemistry, City University of Hong KongInstitute of Biodiversity, Animal Health and Comparative Medicine, University of GlasgowDepartment of Chemistry, City University of Hong KongDepartment of Chemistry, City University of Hong KongDepartment of Chemistry, City University of Hong KongDepartment of Chemistry, City University of Hong KongFaculty of Health Sciences, University of MacauDepartment of Chemistry, City University of Hong KongApplied Oral Sciences and Community Dental Care, University of Hong KongDepartment of Chemistry, City University of Hong KongDepartment of Chemistry, City University of Hong KongDepartment of Chemistry, City University of Hong KongAbstract 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.https://doi.org/10.1038/s41598-021-91765-4
collection	DOAJ
language	English
format	Article
sources	DOAJ
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
spellingShingle	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 Scientific Reports
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 Publishing Group
series	Scientific Reports
issn	2045-2322
publishDate	2021-06-01
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.
url	https://doi.org/10.1038/s41598-021-91765-4
work_keys_str_mv	AT miaodong binganovelantimicrobialpeptideisolatedfromjapanesemedakaplasmatargetsbacterialenvelopestressresponsebysuppressingcpxrexpression AT shuhinkwok binganovelantimicrobialpeptideisolatedfromjapanesemedakaplasmatargetsbacterialenvelopestressresponsebysuppressingcpxrexpression AT josephlhumble binganovelantimicrobialpeptideisolatedfromjapanesemedakaplasmatargetsbacterialenvelopestressresponsebysuppressingcpxrexpression AT yiminliang binganovelantimicrobialpeptideisolatedfromjapanesemedakaplasmatargetsbacterialenvelopestressresponsebysuppressingcpxrexpression AT szewingtang binganovelantimicrobialpeptideisolatedfromjapanesemedakaplasmatargetsbacterialenvelopestressresponsebysuppressingcpxrexpression AT kinhungtang binganovelantimicrobialpeptideisolatedfromjapanesemedakaplasmatargetsbacterialenvelopestressresponsebysuppressingcpxrexpression AT mankittse binganovelantimicrobialpeptideisolatedfromjapanesemedakaplasmatargetsbacterialenvelopestressresponsebysuppressingcpxrexpression AT joshhaipenglei binganovelantimicrobialpeptideisolatedfromjapanesemedakaplasmatargetsbacterialenvelopestressresponsebysuppressingcpxrexpression AT rajkumarramalingam binganovelantimicrobialpeptideisolatedfromjapanesemedakaplasmatargetsbacterialenvelopestressresponsebysuppressingcpxrexpression AT mohamadkoohimoghadam binganovelantimicrobialpeptideisolatedfromjapanesemedakaplasmatargetsbacterialenvelopestressresponsebysuppressingcpxrexpression AT doriswaitingau binganovelantimicrobialpeptideisolatedfromjapanesemedakaplasmatargetsbacterialenvelopestressresponsebysuppressingcpxrexpression AT hongyansun binganovelantimicrobialpeptideisolatedfromjapanesemedakaplasmatargetsbacterialenvelopestressresponsebysuppressingcpxrexpression AT yunwahlam binganovelantimicrobialpeptideisolatedfromjapanesemedakaplasmatargetsbacterialenvelopestressresponsebysuppressingcpxrexpression
_version_	1721379445500018688

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

Similar Items