Human α-Defensin-5 Efficiently Neutralizes Clostridioides difficile Toxins TcdA, TcdB, and CDT.


:Infections with the pathogenic bacterium Clostridioides (C.) difficile are coming more into focus, in particular in hospitalized patients after antibiotic treatment. C. difficile produces the exotoxins TcdA and TcdB. Since some years, hypervirulent strains are described, which produce in addition the binary actin ADP-ribosylating toxin CDT. These strains are associated with more severe clinical presentations and increased morbidity and frequency. Once in the cytosol of their target cells, the catalytic domains of TcdA and TcdB glucosylate and thereby inactivate small Rho-GTPases whereas the enzyme subunit of CDT ADP-ribosylates G-actin. Thus, enzymatic activity of the toxins leads to destruction of the cytoskeleton and breakdown of the epidermal gut barrier integrity. This causes clinical symptoms ranging from mild diarrhea to life-threatening pseudomembranous colitis. Therefore, pharmacological inhibition of the secreted toxins is of peculiar medical interest. Here, we investigated the neutralizing effect of the human antimicrobial peptide α-defensin-5 toward TcdA, TcdB, and CDT in human cells. The toxin-neutralizing effects of α-defensin-5 toward TcdA, TcdB, and CDT as well as their medically relevant combination were demonstrated by analyzing toxins-induced changes in cell morphology, intracellular substrate modification, and decrease of trans-epithelial electrical resistance. For TcdA, the underlying mode of inhibition is most likely based on the formation of inactive toxin-defensin-aggregates whereas for CDT, the binding- and transport-component might be influenced. The application of α-defensin-5 delayed intoxication of cells in a time- and concentration-dependent manner. Due to its effect on the toxins, α-defensin-5 should be considered as a candidate to treat severe C. difficile-associated diseases.


Front Pharmacol


Korbmacher M,Fischer S,Landenberger M,Papatheodorou P,Aktories K,Barth H




Has Abstract


2020-08-12 00:00:00








  • Corrigendum: Safety Profiles of Tripterygium wilfordii Hook F: A Systematic Review and Meta-Analysis.

    abstract::[This corrects the article on p. 402 in vol. 7, PMID: 27877128.]. ...

    journal_title:Frontiers in pharmacology

    pub_type: 已发布勘误


    authors: Zhang C,Sun PP,Guo HT,Liu Y,Li J,He XJ,Lu AP

    更新日期:2017-02-15 00:00:00

  • The Evaluation of Geroprotective Effects of Selected Flavonoids in Drosophila melanogaster and Caenorhabditis elegans.

    abstract::Flavonoids is an intensively studied group of natural compounds with antioxidant, antineoplastic, antihyperglycemic, cardioprotective, and neuroprotective properties. The present study intends to investigate the geroprotective action of three selected flavonoids (naringin, luteolin, chrysin) in two model organisms, Ca...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Lashmanova E,Zemskaya N,Proshkina E,Kudryavtseva A,Volosnikova M,Marusich E,Leonov S,Zhavoronkov A,Moskalev A

    更新日期:2017-12-07 00:00:00

  • Ubc9 Attenuates Myocardial Ischemic Injury Through Accelerating Autophagic Flux.

    abstract:Aims:SUMOylation is a post-translational modification that plays a crucial role in the cellular stress response. We aimed to demonstrate whether and how the SUMO E2 conjugation enzyme Ubc9 affects acute myocardial ischemic (MI) injury. Methods and Results:Adenovirus expressing Ubc9 was administrated by multipoint inje...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Xiao Q,Chen XH,Jiang RC,Chen SY,Chen KF,Zhu X,Zhang XL,Huang JJ,Qin Y,Zhang GP,Yi Q,Luo JD

    更新日期:2020-09-15 00:00:00

  • GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells.

    abstract::Clinical studies have shown that Selank had an anxiolytic effect comparable to that of classical benzodiazepine drugs, which can enhance the inhibitory effect of GABA by allosteric modulation of GABAA receptors. These data suggest that the molecular mechanism of the effect of Selank may also be related to its ability ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Filatova E,Kasian A,Kolomin T,Rybalkina E,Alieva A,Andreeva L,Limborska S,Myasoedov N,Pavlova G,Slominsky P,Shadrina M

    更新日期:2017-02-28 00:00:00

  • Research Progress and Prospect of Nanoplatforms for Treatment of Oral Cancer.

    abstract::Oral cancers refer to malignant tumors associated with high morbidity and mortality, and oral squamous cell carcinoma accounts for the majority of cases. It is an important part of head and neck, and oral cancer is one of the six most common cancers in the world. At present, the traditional treatment methods for oral ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审


    authors: Zhao Z,Li D,Wu Z,Wang Q,Ma Z,Zhang C

    更新日期:2020-12-17 00:00:00

  • Use of Oral Corticosteroids and Risk of Hip Fracture in the Elderly in a Case-Control Study.

    abstract::Aim: Little is known regarding the relationship between use of oral corticosteroids and hip fracture in the elderly in Taiwan. The aim of the study was to examine this issue. Methods: A retrospective population-based case-control study using the database of the Taiwan National Health Insurance Program (2000-2013) was ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Lai SW,Lin CL,Liao KF

    更新日期:2017-09-11 00:00:00

  • TNF-α-Induced cPLA2 Expression via NADPH Oxidase/Reactive Oxygen Species-Dependent NF-κB Cascade on Human Pulmonary Alveolar Epithelial Cells.

    abstract::Tumor necrosis factor-α (TNF-α) triggers activation of cytosolic phospholipase A2 (cPLA2) and then enhancing the synthesis of prostaglandin (PG) in inflammatory diseases. However, the detailed mechanisms of TNF-α induced cPLA2 expression were not fully defined in human pulmonary alveolar epithelial cells (HPAEpiCs). W...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Lin CC,Lin WN,Cho RL,Wang CY,Hsiao LD,Yang CM

    更新日期:2016-11-25 00:00:00

  • Rejuveinix Shows a Favorable Clinical Safety Profile in Human Subjects and Exhibits Potent Preclinical Protective Activity in the Lipopolysaccharide-Galactosamine Mouse Model of Acute Respiratory Distress Syndrome and Multi-Organ Failure.

    abstract::Background: New treatment platforms that can prevent acute respiratory distress syndrome (ARDS) or reduce its mortality rate in high-risk coronavirus disease 2019 (COVID-19) patients, such as those with an underlying cancer, are urgently needed. Rejuveinix (RJX) is an intravenous formulation of anti-oxidants and anti-...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Uckun FM,Carlson J,Orhan C,Powell J,Pizzimenti NM,van Wyk H,Ozercan IH,Volk M,Sahin K

    更新日期:2020-11-10 00:00:00

  • Immune Checkpoint Inhibitor Toxicity in Head and Neck Cancer: From Identification to Management.

    abstract::Benefiting from the continuously clarifying underlying biology of immune checkpoints and ligand-receptor interactions, the emergence of new anticancer treatment strategy, immunotherapy has shown substantial benefits on several liquid and solid tumors. Immune checkpoint inhibitors (ICIs) can block the negative regulato...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审


    authors: Wang H,Mustafa A,Liu S,Liu J,Lv D,Yang H,Zou J

    更新日期:2019-10-23 00:00:00

  • Digoxin and Amiodarone on the Risk of Ischemic Stroke in Atrial Fibrillation: An Observational Study.

    abstract::Purpose: The present study compared the risk of ischemic stroke in atrial fibrillation (AF) patients receiving digoxin and amiodarone. Methods: A retrospective cohort study was conducted using the longitudinal population-based database of Taiwan's National Health Insurance program. Patients with AF who received amioda...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Lai KC,Chen SJ,Lin CS,Yang FC,Lin CL,Hsu CW,Huang WC,Kao CH

    更新日期:2018-05-07 00:00:00

  • MiR-3188 Inhibits Non-small Cell Lung Cancer Cell Proliferation Through FOXO1-Mediated mTOR-p-PI3K/AKT-c-JUN Signaling Pathway.

    abstract::This study investigated the role of miR-3188 on the proliferation of non-small cell lung cancer cells and its relationship to FOXO1-modulated feedback loop. Two non-small cell lung cancer (NSCLC) cell lines A549 and H1299 were used. RNA silencing was achieved by lentiviral transfection. Cell proliferation was assessed...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Wang C,Liu E,Li W,Cui J,Li T

    更新日期:2018-12-11 00:00:00

  • Peroxisome proliferator-activated receptor alpha, PPARα, directly regulates transcription of cytochrome P450 CYP2C8.

    abstract::The cytochrome P450, CYP2C8, metabolizes more than 60 clinically used drugs as well as endogenous substances including retinoic acid and arachidonic acid. However, predictive factors for interindividual variability in the efficacy and toxicity of CYP2C8 drug substrates are essentially lacking. Recently we demonstrated...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Thomas M,Winter S,Klumpp B,Turpeinen M,Klein K,Schwab M,Zanger UM

    更新日期:2015-11-04 00:00:00

  • Current State and Future Prospects of Direct-to-Consumer Pharmacogenetics.

    abstract::Direct-to-consumer (DTC) DNA testing has grown from contentious beginnings into a global industry, by providing a wide range of personal genomic information directly to its clients. These companies, typified by the well-established 23andMe, generally carry out a gene-chip analysis of single-nucleotide polymorphisms (S...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Chua EW,Kennedy MA

    更新日期:2012-08-20 00:00:00

  • Selective Serotonin Reuptake Inhibitor Pharmaco-Omics: Mechanisms and Prediction.

    abstract::Selective serotonin reuptake inhibitors (SSRIs) are a standard of care for the pharmacotherapy of patients suffering from Major Depressive Disorder (MDD). However, only one-half to two-thirds of MDD patients respond to SSRI therapy. Recently, a "multiple omics" research strategy was applied to identify genetic differe...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审


    authors: Nguyen TTL,Liu D,Ho MF,Athreya AP,Weinshilboum R

    更新日期:2021-01-11 00:00:00

  • Bavachin Protects Human Aortic Smooth Muscle Cells Against β-Glycerophosphate-Mediated Vascular Calcification and Apoptosis via Activation of mTOR-Dependent Autophagy and Suppression of β-Catenin Signaling.

    abstract::Vascular calcification is a major complication of cardiovascular disease and chronic renal failure. Autophagy help to maintain a stable internal and external environment that is important for modulating arteriosclerosis, but its pathogenic mechanism is far from clear. Here, we aimed to identify the bioactive compounds...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: He HQ,Law BYK,Zhang N,Qiu CL,Qu YQ,Wu AG,Han Y,Song Q,Zheng WL,Liu Y,He YZ,Wong VKW

    更新日期:2019-12-19 00:00:00

  • Tacrolimus Updated Guidelines through popPK Modeling: How to Benefit More from CYP3A Pre-emptive Genotyping Prior to Kidney Transplantation.

    abstract::Tacrolimus (Tac) is a profoundly effective immunosuppressant that reduces the risk of rejection after solid organ transplantation. However, its use is hampered by its narrow therapeutic window along with its highly variable pharmacological (pharmacokinetic [PK] and pharmacodynamic [PD]) profile. Part of this variabili...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Woillard JB,Mourad M,Neely M,Capron A,van Schaik RH,van Gelder T,Lloberas N,Hesselink DA,Marquet P,Haufroid V,Elens L

    更新日期:2017-06-08 00:00:00

  • Fasudil, a Rho-Kinase Inhibitor, Exerts Cardioprotective Function in Animal Models of Myocardial Ischemia/Reperfusion Injury: A Meta-Analysis and Review of Preclinical Evidence and Possible Mechanisms.

    abstract::Fasudil, a Rho-kinase inhibitor, has shown outstanding therapeutic effects against cerebral vasospasm after subarachnoid hemorrhage (SAH) in humans. Studies show various biological effects of fasudil in the cardiovascular system. We conducted a preclinical systematic review to determine the efficacy and possible mecha...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Huang YY,Wu JM,Su T,Zhang SY,Lin XJ

    更新日期:2018-10-01 00:00:00

  • Anti-Inflammatory Effect of a TCM Formula Li-Ru-Kang in Rats With Hyperplasia of Mammary Gland and the Underlying Biological Mechanisms.

    abstract::Li-Ru-Kang (LRK), a formula of eight traditional Chinese medicines (TCM), has been used to treat hyperplasia of mammary gland (HMG) in TCM clinics. However, how LRK works in HMG patients is unclear. To explore the possible mechanisms of LRK against HMG, the network pharmacology was used to screen the potential targets...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Wang Y,Wei S,Gao T,Yang Y,Lu X,Zhou X,Li H,Wang T,Qian L,Zhao Y,Zou W

    更新日期:2018-11-20 00:00:00

  • Perspectives Regarding the Role of Biochanin A in Humans.

    abstract::Biochanin A (BCA) is an isoflavone mainly found in red clover with poor solubility and oral absorption that is known to have various effects, including anti-inflammatory, estrogen-like, and glucose and lipid metabolism modulatory activity, as well as cancer preventive, neuroprotective, and drug interaction effects. BC...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审


    authors: Yu C,Zhang P,Lou L,Wang Y

    更新日期:2019-07-12 00:00:00

  • Metabolomics Reveals the Efficacy of Caspase Inhibition for Saikosaponin D-Induced Hepatotoxicity.

    abstract::Saikosaponin d (SSd) is a major hepatoprotective component of saikosaponins derived from Radix Bupleuri, which was also linked to hepatotoxicity. Previous studies have demonstrated that caspases play a key role in SSd-induced liver cell death. Our in vitro and in vivo studies also showed that treatment with caspase in...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Zhang QQ,Huang WQ,Gao YQ,Han ZD,Zhang W,Zhang ZJ,Xu FG

    更新日期:2018-07-06 00:00:00

  • Advances and Challenges of Liposome Assisted Drug Delivery.

    abstract::The application of liposomes to assist drug delivery has already had a major impact on many biomedical areas. They have been shown to be beneficial for stabilizing therapeutic compounds, overcoming obstacles to cellular and tissue uptake, and improving biodistribution of compounds to target sites in vivo. This enables...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审


    authors: Sercombe L,Veerati T,Moheimani F,Wu SY,Sood AK,Hua S

    更新日期:2015-12-01 00:00:00

  • Structures Illuminate Cardiac Ion Channel Functions in Health and in Long QT Syndrome.

    abstract::The cardiac action potential is critical to the production of a synchronized heartbeat. This electrical impulse is governed by the intricate activity of cardiac ion channels, among them the cardiac voltage-gated potassium (Kv) channels KCNQ1 and hERG as well as the voltage-gated sodium (Nav) channel encoded by SCN5A. ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审


    authors: Brewer KR,Kuenze G,Vanoye CG,George AL Jr,Meiler J,Sanders CR

    更新日期:2020-05-04 00:00:00

  • Hippocampal Hyperactivity as a Druggable Circuit-Level Origin of Aberrant Salience in Schizophrenia.

    abstract::The development of current neuroleptics was largely aiming to decrease excessive dopaminergic signaling in the striatum. However, the notion that abnormal dopamine creates psychotic symptoms by causing an aberrant assignment of salience that drives maladaptive learning chronically during disease development suggests a...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审


    authors: Kätzel D,Wolff AR,Bygrave AM,Bannerman DM

    更新日期:2020-10-16 00:00:00

  • Chidamide Inhibits Acute Myeloid Leukemia Cell Proliferation by lncRNA VPS9D1-AS1 Downregulation via MEK/ERK Signaling Pathway.

    abstract::Irregular histone modification and aberrant lncRNAs expression are closely related to the occurrence of tumors including acute myeloid leukemia (AML). However, the effects and specific underlying molecular mechanism of histone deacetylase inhibitors on lncRNA expression in AML cells are unclear. Here, we reported the ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Lin L,Que Y,Lu P,Li H,Xiao M,Zhu X,Li D

    更新日期:2020-10-19 00:00:00

  • The Role of Specialized Pro-Resolving Mediators in Cystic Fibrosis Airways Disease.

    abstract::Cystic Fibrosis (CF) is a recessive genetic disease due to mutations of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene encoding the CFTR chloride channel. The ion transport abnormalities related to CFTR mutation generate a dehydrated airway surface liquid (ASL) layer, which is responsible for an a...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审


    authors: Briottet M,Shum M,Urbach V

    更新日期:2020-09-02 00:00:00

  • Artificial Intelligence-Based Multiclass Classification of Benign or Malignant Mucosal Lesions of the Stomach.

    abstract::Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. It takes some time from chronic gastritis to develop in GC. Early detection of GC will help patients obtain timely treatment. Understanding disease evolution is crucial for the prevention and treatment of GC. Here, we present a convolu...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Ma B,Guo Y,Hu W,Yuan F,Zhu Z,Yu Y,Zou H

    更新日期:2020-10-02 00:00:00

  • Differential Patterns of Adherence to Opioid Therapy in Opioid Naïve and Opioid Existing Patients With Different Age Groups.

    abstract::Limited data are available on the adherence to opioid therapy and the influence of different patient groups on adherence. This study examined the patterns of adherence in opioid naïve and opioid existing patients with varying age and gender. This retrospective cohort study was conducted using the prescription database...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Zin CS,Taufek NH,Ahmad MM

    更新日期:2019-10-29 00:00:00

  • Tyrosine phosphorylation of botulinum neurotoxin protease domains.

    abstract::Botulinum neurotoxins are most potent of all toxins. Their N-terminal light chain domain (Lc) translocates into peripheral cholinergic neurons to exert its endoproteolytic action leading to muscle paralysis. Therapeutic development against these toxins is a major challenge due to their in vitro and in vivo structural ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Toth S,Brueggmann EE,Oyler GA,Smith LA,Hines HB,Ahmed SA

    更新日期:2012-06-04 00:00:00

  • Ferulic Acid Protects Hyperglycemia-Induced Kidney Damage by Regulating Oxidative Insult, Inflammation and Autophagy.

    abstract::Oxidative insult, inflammation, apoptosis and autophagy play a pivotal role in the etiology of diabetic nephropathy, a global health concern. Ferulic acid, a phytochemical, is reported to protect against varied diseased conditions. However, the ameliorative role and mechanisms of ferulic acid in averting STZ-mediated ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Chowdhury S,Ghosh S,Das AK,Sil PC

    更新日期:2019-02-05 00:00:00

  • Corrigendum: Voltage-controlled enzymes: the new Janus Bifrons.

    abstract::[This corrects the article on p. 161 in vol. 3, PMID: 22993507.]. ...

    journal_title:Frontiers in pharmacology

    pub_type: 已发布勘误


    authors: Villalba-Galea CA

    更新日期:2015-05-29 00:00:00