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MiRNA863-3p sequentially targets negative immune regulator ARLPKs and positive regulator SERRATE upon bacterial infection.

ABSTRACT: Plant small RNAs play important roles in gene regulation during pathogen infection. Here we show that miR863-3p is induced by the bacterial pathogen Pseudomonas syringae carrying various effectors. Early during infection, miR863-3p silences two negative regulators of plant defence, atypical receptor-like pseudokinase1 (ARLPK1) and ARLPK2, both lacking extracellular domains and kinase activity, through mRNA degradation to promote immunity. ARLPK1 associates with, and may function through another negative immune regulator ARLPK1-interacting receptor-like kinase 1 (AKIK1), an active kinase with an extracellular domain. Later during infection, miR863-3p silences SERRATE, which is essential for miRNA accumulation and positively regulates defence, through translational inhibition. This results in decreased miR863-3p levels, thus forming a negative feedback loop to attenuate immune responses after successful defence. This is an example of a miRNA that sequentially targets both negative and positive regulators of immunity through two modes of action to fine-tune the timing and amplitude of defence responses.

SUBMITTER: Niu D

PROVIDER: S-EPMC4848489 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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miRNA863-3p sequentially targets negative immune regulator ARLPKs and positive regulator SERRATE upon bacterial infection.

Niu Dongdong D Lii Yifan E YE Chellappan Padmanabhan P Lei Lei L Peralta Karl K Jiang Chunhao C Guo Jianhua J Coaker Gitta G Jin Hailing H

Nature communications 20160425

Plant small RNAs play important roles in gene regulation during pathogen infection. Here we show that miR863-3p is induced by the bacterial pathogen Pseudomonas syringae carrying various effectors. Early during infection, miR863-3p silences two negative regulators of plant defence, atypical receptor-like pseudokinase1 (ARLPK1) and ARLPK2, both lacking extracellular domains and kinase activity, through mRNA degradation to promote immunity. ARLPK1 associates with, and may function through another ...[more]

PMID: 27108563

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Project description:Antimicrobial resistance (AMR) poses a significant worldwide public health crisis that continues to threaten our ability to successfully treat bacterial infections. With the decline in effectiveness of conventional antimicrobial therapies and the lack of new antibiotic pipelines, there is a renewed interest in exploring the potential of metal-based antimicrobial compounds. Antimony-based compounds with a long history of use in medicine have re-emerged as potential antimicrobial agents. We previously synthesized a series of novel organoantimony(V) compounds complexed with cyanoximates with a strong potential of antimicrobial activity against several AMR bacterial and fungal pathogens. Here, five selected compounds were studied for their antibacterial efficacy against three important bacterial pathogens: Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus. Among five tested compounds, SbPh4ACO showed antimicrobial activity against all three bacterial strains with the MIC of 50-100 µg/mL. The minimum bactericidal concentration/MIC values were less than or equal to 4 indicating that the effects of SbPh4ACO are bactericidal. Moreover, ultra-thin electron microscopy revealed that SbPh4ACO treatment caused membrane disruption in all three strains, which was further validated by increased membrane permeability. We also showed that SbPh4ACO acted synergistically with the antibiotics, polymyxin B and cefoxitin used to treat AMR strains of P. aeruginosa and S. aureus, respectively, and that at synergistic MIC concentration 12.5 µg/mL, its cytotoxicity against the cell lines, Hela, McCoy, and A549 dropped below the threshold. Overall, the results highlight the antimicrobial potential of novel antimony-based compound, SbPh4ACO, and its use as a potentiator of other antibiotics against both Gram-positive and Gram-negative bacterial pathogens.ImportanceAntibiotic resistance presents a critical global public health crisis that threatens our ability to combat bacterial infections. In light of the declining efficacy of traditional antibiotics, the use of alternative solutions, such as metal-based antimicrobial compounds, has gained renewed interest. Based on the previously synthesized innovative organoantimony(V) compounds, we selected and further characterized the antibacterial efficacy of five of them against three important Gram-positive and Gram-negative bacterial pathogens. Among these compounds, SbPh4ACO showed broad-spectrum bactericidal activity, with membrane-disrupting effects against all three pathogens. Furthermore, we revealed the synergistic potential of SbPh4ACO when combined with antibiotics, such as cefoxitin, at concentrations that exert no cytotoxic effects tested on three mammalian cell lines. This study offers the first report on the mechanisms of action of novel antimony-based antimicrobial and presents the therapeutic potential of SbPh4ACO in combating both Gram-positive and Gram-negative bacterial pathogens while enhancing the efficacy of existing antibiotics.

Dataset Information

MiRNA863-3p sequentially targets negative immune regulator ARLPKs and positive regulator SERRATE upon bacterial infection.

Publications

miRNA863-3p sequentially targets negative immune regulator ARLPKs and positive regulator SERRATE upon bacterial infection.

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