RRC ID 70536
Author Dong M, Kwok SH, Humble JL, Liang Y, Tang SW, Tang KH, Tse MK, Lei JH, Ramalingam R, Koohi-Moghadam M, Au DWT, Sun H, Lam YW.
Title BING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expression.
Journal Sci Rep
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.
Volume 11(1)
Pages 12219
Published 2021-6-9
DOI 10.1038/s41598-021-91765-4
PII 10.1038/s41598-021-91765-4
PMID 34108601
PMC PMC8190156
MeSH Animals Anti-Bacterial Agents / pharmacology* Antimicrobial Cationic Peptides / isolation & purification Antimicrobial Cationic Peptides / pharmacology* Bacteria / drug effects* Bacteria / growth & development Bacterial Proteins / antagonists & inhibitors* Drug Resistance, Multiple, Bacterial / drug effects* Gene Expression Regulation, Bacterial / drug effects* Oryzias Stress, Physiological*
IF 3.998
Resource
Prokaryotes E. coli BW25113 JW3883-AM