Alpha-1 antitrypsin inhibits pertussis toxin.

Pertussis (whooping cough) is a vaccine-preventable but re-emerging, highly infectious respiratory disease caused by Bordetella pertussis. There are currently no effective treatments for pertussis, complicating care for nonvaccinated individuals, especially newborns. Disease manifestations are predominantly caused by pertussis toxin (PT), a pivotal virulence factor classified as an ADP-ribosylating AB-type protein toxin.

A naturally occurring 22-amino acid fragment of human hemoglobin A inhibits autophagy and HIV-1.

Autophagy is an evolutionarily ancient catabolic pathway and has recently emerged as an integral part of the innate immune system. While the core machinery of autophagy is well defined, the physiological regulation of autophagy is less understood. Here, we identify a C-terminal fragment of human hemoglobin A (HBA1, amino acids 111-132) in human bone marrow as a fast-acting non-inflammatory inhibitor of autophagy initiation.

The antiarrhythmic drugs amiodarone and dronedarone inhibit intoxication of cells with pertussis toxin.

Pertussis toxin (PT) is a virulent factor produced by Bordetella pertussis, the causative agent of whooping cough. PT exerts its pathogenic effects by ADP-ribosylating heterotrimeric G proteins, disrupting cellular signaling pathways. Here, we investigate the potential of two antiarrhythmic drugs, amiodarone and dronedarone, in mitigating PT-induced cellular intoxication.

Inhibition of Clostridioides difficile toxins TcdA and TcdB by the amiodarone derivative dronedarone.

The dreaded nosocomial pathogen Clostridioides difficile causes diarrhea and severe inflammation of the colon, especially after the use of certain antibiotics. The bacterium releases two deleterious toxins, TcdA and TcdB, into the gut, which are mainly responsible for the symptoms of C. difficile-associated diseases (CDADs).

Antimicrobial effects of silver nanoparticle-microspots on the mechanical properties of single bacteria.

Silver nanoparticles (AgNPs) conjugated with polymers are well-known for their powerful and effective antimicrobial properties. In particular, the incorporation of AgNPs in biocompatible catecholamine-based polymers, such as polydopamine (PDA), has recently shown promising antimicrobial activity, due to the synergistic effects of the AgNPs, silver(I) ions released and PDA. In this study, we generated AgNPs-PDA-patterned surfaces by localised electrochemical depositions, using a double potentiostatic method scanning electrochemical cell microscopy (SECCM).

Synthesis of biologically active Shiga toxins in cell-free systems.

Shiga toxins (Stx) produced by pathogenic bacteria can cause mild to severe diseases in humans. Thus, the analysis of such toxins is of utmost importance. As an AB toxin, Stx consist of a catalytic A-subunit acting as a ribosome-inactivating protein (RIP) and a B-pentamer binding domain.

The Chaperonin TRiC/CCT Inhibitor HSF1A Protects Cells from Intoxication with Pertussis Toxin.

Pertussis toxin (PT) is a bacterial AB-toxin produced by and a major molecular determinant of pertussis, also known as whooping cough, a highly contagious respiratory disease. In this study, we investigate the protective effects of the chaperonin TRiC/CCT inhibitor, HSF1A, against PT-induced cell intoxication. TRiC/CCT is a chaperonin complex that facilitates the correct folding of proteins, preventing misfolding and aggregation, and maintaining cellular protein homeostasis.

Trauma-toxicology: concepts, causes, complications.

Trauma and toxic substances are connected in several aspects. On the one hand, toxic substances can be the reason for traumatic injuries in the context of accidental or violent and criminal circumstances. Examples for the first scenario is the release of toxic gases, chemicals, and particles during house fires, and for the second scenario, the use of chemical or biological weapons in the context of terroristic activities.

Surface functionalization affects the retention and bio-distribution of orally administered mesoporous silica nanoparticles in a colitis mouse model.

Besides the many advantages of oral drug administration, challenges like premature drug degradation and limited bioavailability in the gastro-intestinal tract (GIT) remain. A prolonged residence time in the GIT is beneficial for enhancing the therapeutic outcome when treating diseases associated with an increased intestinal clearance rate, like inflammatory bowel disease (IBD). In this study, we synthesized rod-shaped mesoporous silica nanoparticles (MSNs) functionalized with polyethylene glycol (PEG) or hyaluronic acid (HA) and investigated their bio-distribution upon oral administration in vivo.

Thin-Film Waveguide Laser Spectroscopy: A Novel Platform for Bacterial Analysis.

Bacterial sensing based on quantum cascade laser spectroscopy coupled with diamond or gallium arsenide thin-film waveguides is a novel analytical tool for gaining high-resolution infrared spectroscopic information of planktonic and sessile bacteria, as shown in the present study for . During observation periods of up to 24 h, diamond and gallium arsenide thin-film waveguide laser spectroscopy was compared to information obtained via conventional Fourier transform infrared spectroscopy. The proliferation behavior of at those surfaces was complementarily investigated using atomic force microscopy and scanning electron microscopy.

Exploring the inhibitory potential of the antiarrhythmic drug amiodarone against toxins TcdA and TcdB.

The intestinal pathogen is the leading cause of antibiotic-associated diarrhea and pseudomembranous colitis in humans. The symptoms of -associated diseases (CDADs) are directly associated with the pathogen's toxins TcdA and TcdB, which enter host cells and inactivate Rho and/or Ras GTPases by glucosylation. Membrane cholesterol is crucial during the intoxication process of TcdA and TcdB, and likely involved during pore formation of both toxins in endosomal membranes, a key step after cellular uptake for the translocation of the glucosyltransferase domain of both toxins from endosomes into the host cell cytosol.

Domperidone Inhibits C2 Toxin and Toxin.

toxin (PT) and C2 toxin are ADP-ribosylating toxins causing severe diseases in humans and animals. They share a common translocation mechanism requiring the cellular chaperones Hsp90 and Hsp70, cyclophilins, and FK506-binding proteins to transport the toxins' enzyme subunits into the cytosol. Inhibitors of chaperone activities have been shown to reduce the amount of transported enzyme subunits into the cytosol of cells, thus protecting cells from intoxication by these toxins.

Inhibition of Pertussis Toxin by Human α-Defensins-1 and -5: Differential Mechanisms of Action.

Whooping cough is a severe childhood disease, caused by the bacterium , which releases pertussis toxin (PT) as a major virulence factor. Previously, we identified the human antimicrobial peptides α-defensin-1 and -5 as inhibitors of PT and demonstrated their capacity to inhibit the activity of the PT enzyme subunit PTS1. Here, the underlying mechanism of toxin inhibition was investigated in more detail, which is essential for developing the therapeutic potential of these peptides.

The C2 Toxin Subunit C2IIa Delivers Enzymes with Positively Charged N-Termini into the Cytosol of Target Cells.

The binary () C2 toxin consists of two non-linked proteins. The proteolytically activated binding/transport subunit C2IIa forms barrel-shaped homoheptamers, which bind to cell surface receptors, mediate endocytosis, and translocate the enzyme subunit C2I into the cytosol of target cells. Here, we investigate whether C2IIa can be harnessed as a transporter for proteins/enzymes fused to polycationic tags, as earlier demonstrated for the related anthrax toxin transport subunit PA.

Domperidone Protects Cells from Intoxication with Toxins by Inhibiting Hsp70-Assisted Membrane Translocation.

infections cause severe symptoms ranging from diarrhea to pseudomembranous colitis due to the secretion of AB-toxins, TcdA and TcdB. Both toxins are taken up into cells through receptor-mediated endocytosis, autoproteolytic processing and translocation of their enzyme domains from acidified endosomes into the cytosol. The enzyme domains glucosylate small GTPases such as Rac1, thereby inhibiting processes such as actin cytoskeleton regulation.

Parahydrogen-Polarized Fumarate for Preclinical Metabolic Magnetic Resonance Imaging.

We present a versatile method for the preparation of hyperpolarized [1-C]fumarate as a contrast agent for preclinical MRI, using parahydrogen-induced polarization (PHIP). To benchmark this process, we compared a prototype PHIP polarizer to a state-of-the-art dissolution dynamic nuclear polarization (d-DNP) system. We found comparable polarization, volume, and concentration levels of the prepared solutions, while the preparation effort is significantly lower for the PHIP process, which can provide a preclinical dose every 10 min, opposed to around 90 min for d-DNP systems.

Antimicrobial Efficiency of Chitosan and Its Methylated Derivative against Biofilms.

Antimicrobial materials are considered potential alternatives to prevent the development of biofilm-associated contaminations. Concerns regarding synthetic preservatives necessitate the development of innovative and safe natural antimicrobials. In the present study, we discuss the in situ infrared attenuated total reflection spectroscopy (IR-ATR) investigations of the selective antimicrobial efficiency of chitosan in controlling the growth of biofilms.

Atomic force and infrared spectroscopic studies on the role of surface charge for the anti-biofouling properties of polydopamine films.

Antibacterial polymer materials have gained interest due to their capability to inhibit or eradicate biofilms with greater efficiency in comparison with their monomeric counterparts. Among the antimicrobial and anti-biofouling polymers, catecholamine-based polymers - and in particular polydopamine - have been studied due to their favorable adhesion properties, which can be tuned by controlling the pH value. In this study, we used atomic force microscopy (AFM)-based spectroscopy to investigate the relation between the adhesion properties and surface charge density and the pH of electrochemically deposited polydopamine films presenting a dissociation constant of polydopamine of 6.

In situ monitoring of Lentilactobacillus parabuchneri biofilm formation via real-time infrared spectroscopy.

Foodborne pathogenic microorganisms form biofilms at abiotic surfaces, which is a particular challenge in food processing industries. The complexity of biofilm formation requires a fundamental understanding on the involved molecular mechanisms, which may then lead to efficient prevention strategies. In the present study, biogenic amine producing bacteria, i.

C3 Toxin for Selective Delivery of Cargo into Dendritic Cells and Macrophages.

The protein toxin C3bot from is a mono-ADP-ribosyltransferase that selectively intoxicates monocyte-derived cells such as macrophages, osteoclasts, and dendritic cells (DCs) by cytosolic modification of Rho-A, -B, and -C. Here, we investigated the application of C3bot as well as its non-toxic variant C3bot as transporters for selective delivery of cargo molecules into macrophages and DCs. C3bot and C3bot facilitated the uptake of eGFP into early endosomes of human-monocyte-derived macrophages, as revealed by stimulated emission depletion (STED) super-resolution microscopy.

Silver-fluoropolymer (Ag-CF) films: Kinetic study of silver release, and spectroscopic-microscopic insight into the inhibition of P. fluorescens biofilm formation.

Silver-fluoropolymer (Ag-CF) composed of encapsulated bioactive nanophases within a thin polymer coating are promising antimicrobial films with excellent bioactivity. In this contribution, we report on Ag-CF thin films obtained by ion beam co-sputtering, accurately tuning film thickness, and inorganic loading. The Ag-CF films were characterized by spectroscopic and scanning probe microscopy techniques with respect to composition and swelling behavior.

Human α-Defensin-6 Neutralizes Toxins TcdA and TcdB by Direct Binding.

Rising incidences and mortalities have drawn attention to infections (CDIs) in recent years. The main virulence factors of this bacterium are the exotoxins TcdA and TcdB, which glucosylate Rho-GTPases and thereby inhibit Rho/actin-mediated processes in cells. This results in cell rounding, gut barrier disruption and characteristic clinical symptoms.