A Small RNA Transforms the Multidrug Resistance of Pseudomonas aeruginosa to Drug Susceptibility.

Abstract:

:Bacteria with multiple drug resistance (MDR) have become a global issue worldwide, and hundreds of thousands of people's lives are threatened every year. The emergence of novel MDR strains and insufficient development of new antimicrobial agents are the major reasons that limit the choice of antibiotics for the treatment of bacterial infection. Thus, preserving the clinical value of current antibiotics could be one of the effective approaches to resolve this problem. Here we identified numerous novel small RNAs that were downregulated in the MDR clinical isolates of Pseudomonas aeruginosa (P. aeru), and we demonstrated that overexpression of one of these small RNAs (sRNAs), AS1974, was able to transform the MDR clinical strain to drug hypersusceptibility. AS1974 is the master regulator to moderate the expression of several drug resistance pathways, including membrane transporters and biofilm-associated antibiotic-resistant genes, and its expression is regulated by the methylation sites located at the 5' UTR of the gene. Our findings unravel the sRNA that regulates the MDR pathways in clinical isolates of P. aeru. Moreover, transforming bacterial drug resistance to hypersusceptibility using sRNA could be the potential approach for tackling MDR bacteria in the future.

journal_name

Mol Ther Nucleic Acids

authors

Law COK,Huang C,Pan Q,Lee J,Hao Q,Chan TF,Lo NWS,Ang IL,Koon A,Ip M,Chan E,Lau TCK

doi

10.1016/j.omtn.2019.02.011

subject

Has Abstract

pub_date

2019-06-07 00:00:00

pages

218-228

issn

2162-2531

pii

S2162-2531(19)30041-1

journal_volume

16

pub_type

杂志文章
  • Identification and Characterization of an eIF4e DNA Aptamer That Inhibits Proliferation With High Throughput Sequencing.

    abstract::Development of DNA aptamer screens that are both simple and informative can increase the success rate of DNA aptamer selection and induce greater adoption. High eIF4e levels contribute to malignancies, thus eIF4e presents itself as a valuable target for DNA aptamer-based inhibition screen. Here, we demonstrate a metho...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2014.70

    authors: Guo WM,Kong KW,Brown CJ,Quah ST,Yeo HL,Hoon S,Seow Y

    更新日期:2014-12-16 00:00:00

  • Multi-pathway Protective Effects of MicroRNAs on Human Chondrocytes in an In Vitro Model of Osteoarthritis.

    abstract::Osteoarthritis (OA) is the most common degenerative joint disease. One of the main pathogenic factors of OA is thought to be inflammation. Other factors associated with OA are dysregulation of microRNAs, reduced autophagic activity, oxidative stress, and altered metabolism. microRNAs are small non-coding RNAs that are...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2019.07.011

    authors: Al-Modawi RN,Brinchmann JE,Karlsen TA

    更新日期:2019-09-06 00:00:00

  • Preclinical in vivo evaluation of the safety of a multi-shRNA-based gene therapy against HIV-1.

    abstract::Highly active antiretroviral therapy (HAART) has significantly improved the quality of life and the life expectancy of HIV-infected individuals. Still, drug-induced side effects and emergence of drug-resistant viral variants remain important issues that justify the exploration of alternative therapeutic options. One s...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2013.48

    authors: Centlivre M,Legrand N,Klamer S,Liu YP,Jasmijn von Eije K,Bohne M,Rijnstra ES,Weijer K,Blom B,Voermans C,Spits H,Berkhout B

    更新日期:2013-09-03 00:00:00

  • Preclinical Development of a Subcutaneous ALAS1 RNAi Therapeutic for Treatment of Hepatic Porphyrias Using Circulating RNA Quantification.

    abstract::The acute hepatic porphyrias are caused by inherited enzymatic deficiencies in the heme biosynthesis pathway. Induction of the first enzyme 5-aminolevulinic acid synthase 1 (ALAS1) by triggers such as fasting or drug exposure can lead to accumulation of neurotoxic heme intermediates that cause disease symptoms. We hav...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2015.36

    authors: Chan A,Liebow A,Yasuda M,Gan L,Racie T,Maier M,Kuchimanchi S,Foster D,Milstein S,Charisse K,Sehgal A,Manoharan M,Meyers R,Fitzgerald K,Simon A,Desnick RJ,Querbes W

    更新日期:2015-11-03 00:00:00

  • miR-122 Exerts Inhibitory Effects on Osteoblast Proliferation/Differentiation in Osteoporosis by Activating the PCP4-Mediated JNK Pathway.

    abstract::Osteoporosis is characterized by the reduction of bone mineral density and deterioration of bone quality which leads to high risk of fractures. Some microRNAs (miRNAs) have been confirmed as potential modulators of osteoblast differentiation to maintain bone mass maintenance. We aimed to clarify whether miR-122 could ...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2019.11.038

    authors: Meng YC,Lin T,Jiang H,Zhang Z,Shu L,Yin J,Ma X,Wang C,Gao R,Zhou XH

    更新日期:2020-06-05 00:00:00

  • sTAM: An Online Tool for the Discovery of miRNA-Set Level Disease Biomarkers.

    abstract::MicroRNAs (miRNAs) are an important class of small noncoding RNA molecules that serve as excellent biomarkers of various diseases. However, current miRNA biomarkers, including those comprised of multiple miRNAs, work at a single-miRNA level but not at a miRNA-set level, which is defined as a group of miRNAs sharing co...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2020.07.004

    authors: Shi J,Cui Q

    更新日期:2020-09-04 00:00:00

  • Mbd2 Mediates Retinal Cell Apoptosis by Targeting the lncRNA Mbd2-AL1/miR-188-3p/Traf3 Axis in Ischemia/Reperfusion Injury.

    abstract::Recent studies reported that DNA methylation was involved in retinal cell death. Methyl-CpG binding domain protein 2 (Mbd2) is one of the DNA methylation readers. Its role and mechanism of regulation remain unclear. The ischemia/reperfusion (I/R) model in mice primary culture retinal ganglion cells (RGCs) and Mbd2 kno...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2020.01.011

    authors: Ge Y,Zhang R,Feng Y,Li H

    更新日期:2020-03-06 00:00:00

  • E-selectin Targeting PEGylated-thioaptamer Prevents Breast Cancer Metastases.

    abstract::E-selectin is an adhesion molecule expressed on the luminal surface of inflamed blood vessels that mediates hematogenous metastasis by assisting shear-resistant adhesion of circulating tumor cells to the vessel surface under dynamic blood flow. Previously, we developed an E-selectin antagonistic thioaptamer (ESTA) for...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2016.103

    authors: Morita Y,Kamal M,Kang SA,Zhang R,Lokesh GL,Thiviyanathan V,Hasan N,Woo S,Zhao D,Leslie M,Suh S,Razaq W,Rui H,Gorenstein DG,Volk DE,Tanaka T

    更新日期:2016-12-13 00:00:00

  • PAK1 Promotes the Proliferation and Inhibits Apoptosis of Human Spermatogonial Stem Cells via PDK1/KDR/ZNF367 and ERK1/2 and AKT Pathways.

    abstract::Spermatogonial stem cells (SSCs) have significant applications in reproductive and regenerative medicine. However, nothing is known about genes in mediating human SSCs. Here we have explored for the first time the function and mechanism of P21-activated kinase 1 (PAK1) in regulating the proliferation and apoptosis of ...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2018.06.006

    authors: Fu H,Zhang W,Yuan Q,Niu M,Zhou F,Qiu Q,Mao G,Wang H,Wen L,Sun M,Li Z,He Z

    更新日期:2018-09-07 00:00:00

  • Combination of microRNA-21 and microRNA-146a Attenuates Cardiac Dysfunction and Apoptosis During Acute Myocardial Infarction in Mice.

    abstract::Recent studies have revealed the cytoprotective roles of microRNAs (miRNAs) miR-21 and miR-146a against ischemic cardiac injuries. While these studies investigated each of these miRNAs as an independent individual factor, our previous study has suggested the possible interaction between these two miRNAs. The present s...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2016.12

    authors: Huang W,Tian SS,Hang PZ,Sun C,Guo J,Du ZM

    更新日期:2016-03-15 00:00:00

  • Implications of Newly Identified Brain eQTL Genes and Their Interactors in Schizophrenia.

    abstract::Schizophrenia (SCZ) is a devastating genetic mental disorder. Identification of the SCZ risk genes in brains is helpful to understand this disease. Thus, we first used the minimum Redundancy-Maximum Relevance (mRMR) approach to integrate the genome-wide sequence analysis results on SCZ and the expression quantitative ...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2018.05.026

    authors: Cai L,Huang T,Su J,Zhang X,Chen W,Zhang F,He L,Chou KC

    更新日期:2018-09-07 00:00:00

  • Exosomes Derived from miR-143-Overexpressing MSCs Inhibit Cell Migration and Invasion in Human Prostate Cancer by Downregulating TFF3.

    abstract::Exosomes are membrane-enclosed nanovesicles that shuttle active cargoes, such as mRNAs and microRNAs (miRNAs), between different cells. Mesenchymal stem cells (MSCs) are able to migrate to the tumor sites and exert complex functions over tumor progress. We investigated the effect of human bone marrow-derived MSC (BMSC...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2019.08.010

    authors: Che Y,Shi X,Shi Y,Jiang X,Ai Q,Shi Y,Gong F,Jiang W

    更新日期:2019-12-06 00:00:00

  • Mitochondrial DNA Haplogroup N9a Negatively Correlates with Incidence of Hepatocellular Carcinoma in Northern China.

    abstract::Mitochondrial DNA (mtDNA) haplogroups are associated with various types of cancer; however, the molecular mechanisms by which mtDNA haplogroups affect primary hepatocellular carcinoma (HCC) are not known. In this study, we carried out a case-control study on 388 HCC patients and 511 geographically matched asymptomatic...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2019.09.001

    authors: Hua S,Li M,Zhao Q,Wang J,Zhou Y,Liu J,Fang H,Jiang M,Shen L

    更新日期:2019-12-06 00:00:00

  • The Bioactivity of D-/L-Isonucleoside- and 2'-Deoxyinosine-Incorporated Aptamer AS1411s Including DNA Replication/MicroRNA Expression.

    abstract::In this study, chemical modification of 2'-deoxyinosine (2'-dI) and D-/L-isothymidine (D-/L-isoT) was performed on AS1411. They could promote the nucleotide-protein interaction by changing the local conformation. Twenty modified sequences were obtained, FCL-I and FCL-II showed the most noticeable activity improvement....

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2017.09.010

    authors: Fan X,Sun L,Li K,Yang X,Cai B,Zhang Y,Zhu Y,Ma Y,Guan Z,Wu Y,Zhang L,Yang Z

    更新日期:2017-12-15 00:00:00

  • Hairpin Ribozyme Genes Curtail Alcohol Drinking: from Rational Design to in vivo Effects in the Rat.

    abstract::Ribozyme genes were designed to reduce voluntary alcohol drinking in a rat model of alcohol dependence. Acetaldehyde generated from alcohol in the liver is metabolized by the mitochondrial aldehyde dehydrogenase (ALDH2) such that diminishing ALDH2 activity leads to the aversive effects of blood acetaldehyde upon alcoh...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2016.41

    authors: Sapag A,Irrazábal T,Lobos-González L,Muñoz-Brauning CR,Quintanilla ME,Tampier L

    更新日期:2016-07-12 00:00:00

  • The Bipartite Network Projection-Recommended Algorithm for Predicting Long Non-coding RNA-Protein Interactions.

    abstract::With the development of science and biotechnology, many evidences show that ncRNAs play an important role in the development of important biological processes, especially in chromatin modification, cell differentiation and proliferation, RNA progressing, human diseases, etc. Moreover, lncRNAs account for the majority ...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2018.09.020

    authors: Zhao Q,Yu H,Ming Z,Hu H,Ren G,Liu H

    更新日期:2018-12-07 00:00:00

  • CRISPR-Cas9 System as a Versatile Tool for Genome Engineering in Human Cells.

    abstract::Targeted nucleases are influential instruments for intervening in genome revision with great accuracy. RNA-guided Cas9 nucleases produced from clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have noticeably altered the means to modify the genomes of distinct organisms. They can be notabl...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章,评审

    doi:10.1038/mtna.2016.95

    authors: Wang X,Huang X,Fang X,Zhang Y,Wang W

    更新日期:2016-11-15 00:00:00

  • miR-185 Inhibits Fibrogenic Activation of Hepatic Stellate Cells and Prevents Liver Fibrosis.

    abstract::Recent studies have shown the effect of microRNAs on HSC activation and transformation, which is essential for the pathogenesis of liver fibrosis. In our study, we explored the role of miR-185 in liver fibrosis. Plasma miR-185 was detected in hepatitis B virus-related liver fibrosis patients (S2/3, n = 10) by Illumina...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2017.11.010

    authors: Zhou L,Liu S,Han M,Ma Y,Feng S,Zhao J,Lu H,Yuan X,Cheng J

    更新日期:2018-03-02 00:00:00

  • Targeting the PD-1/PD-L1 Immune Evasion Axis With DNA Aptamers as a Novel Therapeutic Strategy for the Treatment of Disseminated Cancers.

    abstract::Blocking the immunoinhibitory PD-1:PD-L1 pathway using monoclonal antibodies has led to dramatic clinical responses by reversing tumor immune evasion and provoking robust and durable antitumor responses. Anti-PD-1 antibodies have now been approved for the treatment of melanoma, and are being clinically tested in a num...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2015.11

    authors: Prodeus A,Abdul-Wahid A,Fischer NW,Huang EH,Cydzik M,Gariépy J

    更新日期:2015-04-28 00:00:00

  • Compatibility and Fidelity of Mirror-Image Thymidine in Transcription Events by T7 RNA Polymerase.

    abstract::Due to highly enzymatic d-stereoselectivity, l-nucleotides (l-2'-deoxynucleoside 5'-triphosphates [l-dNTPs]) are not natural targets of polymerases. In this study, we synthesized series of l-thymidine (l-T)-modified DNA strands and evaluated the processivity of nucleotide incorporation for transcription by T7 RNA poly...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2020.06.023

    authors: Liu Q,Ke Y,Kan Y,Tang X,Li X,He Y,Wu L

    更新日期:2020-09-04 00:00:00

  • Kcnq1ot1/miR-381-3p/ETS2 Axis Regulates Inflammation in Mouse Models of Acute Respiratory Distress Syndrome.

    abstract::Inflammatory mediators play a key role in the pathogenesis of acute respiratory distress syndrome (ARDS). In this study, we aimed to explore the involvement of the Kcnq1 opposite strand/antisense transcript 1 (Kcnq1ot1)/miR-381-3p/E26 transformation-specific proto-oncogene 2 (ETS2) axis in inflammation of lipopolysacc...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2019.10.036

    authors: Jiang X,Yu M,Zhu T,Lou L,Chen X,Li Q,Wei D,Sun R

    更新日期:2020-03-06 00:00:00

  • Macrophage-Derived miRNA-Containing Exosomes Induce Peritendinous Fibrosis after Tendon Injury through the miR-21-5p/Smad7 Pathway.

    abstract::Following tendon injury, the development of fibrotic healing response impairs tendon function and restricts tendon motion. Peritendinous tissue fibrosis poses a major clinical problem in hand surgery. Communication between macrophages and tendon cells has a critical role in regulating the tendon-healing process. Yet, ...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2018.11.006

    authors: Cui H,He Y,Chen S,Zhang D,Yu Y,Fan C

    更新日期:2019-03-01 00:00:00

  • Downregulation of MicroRNA-222 Reduces Insulin Resistance in Rats with PCOS by Inhibiting Activation of the MAPK/ERK Pathway via Pten.

    abstract::Polycystic ovary syndrome (PCOS), characterized by the dysfunction of endocrine metabolism, is a common disease among women. Insulin (INS) resistance (IR) is considered as an obstruction to effective PCOS treatment. Here, we aimed to explore the mechanism by which microRNA-222 (miR-222) affects IR in PCOS via Pten. Qu...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2020.07.014

    authors: Ye H,Liu XJ,Hui Y,Liang YH,Li CH,Wan Q

    更新日期:2020-07-10 00:00:00

  • PPAR Gamma-Regulated MicroRNA 199a-5p Underlies Bone Marrow Adiposity in Aplastic Anemia.

    abstract::Increased propensity of bone marrow-derived mesenchymal stem cells (BM-MSCs) toward adipogenic differentiation has been implicated in the fatty bone marrow and defective hematopoiesis of aplastic anemia (AA). However, the underlying molecular mechanism remains to be investigated. In this study, we found that microRNA ...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2019.07.005

    authors: Zhang X,Liu L,Dou C,Cheng P,Liu L,Liu H,Ren S,Wang C,Jia S,Chen L,Zhang H,Chen M

    更新日期:2019-09-06 00:00:00

  • Lipid Nanoparticle-mediated siRNA Transfer Against PCTAIRE1/PCTK1/Cdk16 Inhibits In Vivo Cancer Growth.

    abstract::PCTAIRE1/CDK16/PCTK1 plays critical roles in cancer cell proliferation and antiapoptosis. To advance our previously published in vitro results with PCTAIRE1 silencing, we examined the in vivo therapeutic potential of this approach by using small interfering RNA (siRNA) encapsulated by lipid nanoparticles. Therapy expe...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2016.40

    authors: Yanagi T,Tachikawa K,Wilkie-Grantham R,Hishiki A,Nagai K,Toyonaga E,Chivukula P,Matsuzawa S

    更新日期:2016-06-28 00:00:00

  • The MicroRNA Biology of the Mammalian Nucleus.

    abstract::MicroRNAs (miRNAs) are a class of genome-encoded small RNAs that are primarily considered to be post-transcriptional negative regulators of gene expression acting in the cytoplasm. Over a decade of research has focused on this canonical paradigm of miRNA function, with many success stories. Indeed, miRNAs have been id...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2014.40

    authors: Roberts TC

    更新日期:2014-08-19 00:00:00

  • One-Step Biallelic and Scarless Correction of a β-Thalassemia Mutation in Patient-Specific iPSCs without Drug Selection.

    abstract::Monogenic disorders (MGDs), which are caused by single gene mutations, have a serious effect on human health. Among these, β-thalassemia (β-thal) represents one of the most common hereditary hematological diseases caused by mutations in the human hemoglobin β (HBB) gene. The technologies of induced pluripotent stem ce...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2016.11.010

    authors: Liu Y,Yang Y,Kang X,Lin B,Yu Q,Song B,Gao G,Chen Y,Sun X,Li X,Bu L,Fan Y

    更新日期:2017-03-17 00:00:00

  • circINSR Promotes Proliferation and Reduces Apoptosis of Embryonic Myoblasts by Sponging miR-34a.

    abstract::As a diverse and abundant class of endogenous RNAs, circular RNAs (circRNAs) participate in processes including cell proliferation and apoptosis. Nevertheless, few researchers have investigated the function of circRNAs in bovine muscle development. Based on existing sequencing data, we identified circINSR. The localiz...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2019.12.032

    authors: Shen X,Zhang X,Ru W,Huang Y,Lan X,Lei C,Chen H

    更新日期:2020-03-06 00:00:00

  • Tat-haFGF14-154 Upregulates ADAM10 to Attenuate the Alzheimer Phenotype of APP/PS1 Mice through the PI3K-CREB-IRE1α/XBP1 Pathway.

    abstract::Acid fibroblast growth factor (aFGF) has shown neuroprotection in Alzheimer's disease (AD) models in previous studies, yet its mechanism is still uncertain. Here we report that the efficacy of Tat-haFGF14-154 is markedly increased when loaded cationic liposomes for intranasal delivery are intranasally administered to ...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2017.05.004

    authors: Meng T,Cao Q,Lei P,Bush AI,Xiang Q,Su Z,He X,Rogers JT,Chiu IM,Zhang Q,Huang Y

    更新日期:2017-06-16 00:00:00

  • miR-146b-5p Enhances the Sensitivity of NSCLC to EGFR Tyrosine Kinase Inhibitors by Regulating the IRAK1/NF-κB Pathway.

    abstract::Although patients with non-small cell lung cancer harboring activating mutations in the epidermal growth factor receptor (EGFR) show good clinical response to EGFR tyrosine kinase inhibitors (TKIs), patients eventually develop acquired resistance. Previous studies have shown that several microRNAs (miRNAs) are involve...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2020.09.015

    authors: Liu YN,Tsai MF,Wu SG,Chang TH,Tsai TH,Gow CH,Wang HY,Shih JY

    更新日期:2020-09-16 00:00:00