Cytoadhesion of Plasmodium falciparum-Infected Red Blood Cells Changes the Expression of Cytokine-, Histone- and Antiviral Protein-Encoding Genes in Brain Endothelial Cells.

Malaria remains a significant global health problem, mainly due to Plasmodium falciparum, which is responsible for most fatal infections. Infected red blood cells (iRBCs) evade spleen clearance by adhering to endothelial cells (ECs), triggering capillary blockage, inflammation, endothelial dysfunction and altered vascular permeability, prompting an endothelial transcriptional response. The iRBC/HBEC-5i model, where iRBCs present IT4var04 (VAR2CSA) on their surface, was used to analyze the effects of iRBC binding on ECs at different temperature (37°C vs.

"Meet the IUPAB councilor"-Thomas Gutsmann.

As one of the twelve newly elected councillors, it is my pleasure to provide a brief biographical sketch for the readers of Biophys. Rev. and the members of the Biophysical Societies.

A synthetic peptide mimic kills Candida albicans and synergistically prevents infection.

More than two million people worldwide are affected by life-threatening, invasive fungal infections annually. Candida species are the most common cause of nosocomial, invasive fungal infections and are associated with mortality rates above 40%. Despite the increasing incidence of drug-resistance, the development of novel antifungal formulations has been limited.

Secretion of the fungal toxin candidalysin is dependent on conserved precursor peptide sequences.

The opportunistic fungal pathogen Candida albicans damages host cells via its peptide toxin, candidalysin. Before secretion, candidalysin is embedded in a precursor protein, Ece1, which consists of a signal peptide, the precursor of candidalysin and seven non-candidalysin Ece1 peptides (NCEPs), and is found to be conserved in clinical isolates. Here we show that the Ece1 polyprotein does not resemble the usual precursor structure of peptide toxins.

The mechanistic basis of the membrane-permeabilizing activities of the virulence-associated protein A (VapA) from Rhodococcus equi.

Pathogenic Rhodococcus equi release the virulence-associated protein A (VapA) within macrophage phagosomes. VapA permeabilizes phagosome and lysosome membranes and reduces acidification of both compartments. Using biophysical techniques, we found that VapA interacts with model membranes in four steps: (i) binding, change of mechanical properties, (ii) formation of specific membrane domains, (iii) permeabilization within the domains, and (iv) pH-specific transformation of domains.

Structural analysis of the NK-lysin-derived peptide NK-2 upon interaction with bacterial membrane mimetics consisting of phosphatidylethanolamine and phosphatidylglycerol.

NK-2 is an antimicrobial peptide derived from helices 3 and 4 of the pore-forming protein of natural killer cells, NK-lysin. It has potent activities against Gram-negative and Gram-positive bacteria, fungi and protozoan parasites without being toxic to healthy human cells. In biophysical assays its membrane activities were found to require phosphatidylglycerol (PG) and phosphatidylethanolamine (PE), lipids which dominate the composition of bacterial membranes.

Structure-function relationships underpin disulfide loop cleavage-dependent activation of Legionella pneumophila lysophospholipase A PlaA.

Legionella pneumophila, the causative agent of a life-threatening pneumonia, intracellularly replicates in a specialized compartment in lung macrophages, the Legionella-containing vacuole (LCV). Secreted proteins of the pathogen govern important steps in the intracellular life cycle including bacterial egress. Among these is the type II secreted PlaA which, together with PlaC and PlaD, belongs to the GDSL phospholipase family found in L.

Influence of Membrane Asymmetry on OmpF Insertion, Orientation and Function.

The effect of asymmetric membranes containing lipopolysaccharides (LPS) on the outer membrane protein F (OmpF) reconstitution, channel orientation, and antibiotic permeation across the outer membrane was investigated. After forming an asymmetric planar lipid bilayer composed of LPS on one and phospholipids on the other side, the membrane channel OmpF was added. The ion current recordings demonstrate that LPS has a strong influence on the OmpF membrane insertion, orientation, and gating.

Toxicological and Safety Pharmacological Profiling of the Anti-Infective and Anti-Inflammatory Peptide Pep19-2.5.

Aspidasept (Pep19-2.5) and its derivative Pep19-4LF ("Aspidasept II") are anti-infective and anti-inflammatory synthetic polypeptides currently in development for application against a variety of moderate to severe bacterial infections that could lead to systemic inflammation, as in the case of severe sepsis and septic shock, as well as application to non-systemic diseases in the case of skin and soft tissue infections (SSTI). In the present study, Aspidasept and Aspidasept II and their part structures were analysed with respect to their toxic behavior in different established models against a variety of relevant cells, and in electrophysiological experiments targeting the hERG channel according to ICH S7B.

CD36-A Host Receptor Necessary for Malaria Parasites to Establish and Maintain Infection.

infected erythrocytes (IEs) present erythrocyte membrane protein 1 proteins (EMP1s) on the cell surface, via which they cytoadhere to various endothelial cell receptors (ECRs) on the walls of human blood vessels. This prevents the parasite from passing through the spleen, which would lead to its elimination. Each isolate has about 60 different EMP1s acting as ligands, and at least 24 ECRs have been identified as interaction partners.

Candidalysin Is the Hemolytic Factor of .

produces an important virulence factor, the hypha-associated -derived secreted peptide toxin candidalysin, which is crucial for the establishment of mucosal and systemic infections. has also long been known to be hemolytic, yet the hemolytic factor has not been clearly identified. Here, we show that candidalysin is the hemolytic factor of .

The ESX-4 substrates, EsxU and EsxT, modulate Mycobacterium abscessus fitness.

ESX type VII secretion systems are complex secretion machineries spanning across the mycobacterial membrane and play an important role in pathogenicity, nutrient uptake and conjugation. We previously reported the role of ESX-4 in modulating Mycobacterium abscessus intracellular survival. The loss of EccB4 was associated with limited secretion of two effector proteins belonging to the WXG-100 family, EsxU and EsxT, and encoded by the esx-4 locus.

Design of Membrane Active Peptides Considering Multi-Objective Optimization for Biomedical Application.

A multitude of membrane active peptides exists that divides into subclasses, such as cell penetrating peptides (CPPs) capable to enter eukaryotic cells or antimicrobial peptides (AMPs) able to interact with prokaryotic cell envelops. Peptide membrane interactions arise from unique sequence motifs of the peptides that account for particular physicochemical properties. Membrane active peptides are mainly cationic, often primary or secondary amphipathic, and they interact with membranes depending on the composition of the bilayer lipids.

Flagellin lysine methyltransferase FliB catalyzes a [4Fe-4S] mediated methyl transfer reaction.

The methyltransferase FliB posttranslationally modifies surface-exposed ɛ-N-lysine residues of flagellin, the protomer of the flagellar filament in Salmonella enterica (S. enterica). Flagellin methylation, reported originally in 1959, was recently shown to enhance host cell adhesion and invasion by increasing the flagellar hydrophobicity.

Mass Spectrometric Quantification of the Antimicrobial Peptide Pep19-2.5 with Stable Isotope Labeling and Acidic Hydrolysis.

Sepsis is the number one cause of death in intensive care units. This life-threatening condition is caused by bacterial infections and triggered by endotoxins of Gram-negative bacteria that leads to an overreaction of the immune system. The synthetic anti-lipopolysaccharide peptide Pep19-2.

Cathelicidin and PMB neutralize endotoxins by multifactorial mechanisms including LPS interaction and targeting of host cell membranes.

Antimicrobial peptides (AMPs) contribute to an effective protection against infections. The antibacterial function of AMPs depends on their interactions with microbial membranes and lipids, such as lipopolysaccharide (LPS; endotoxin). Hyperinflammation induced by endotoxin is a key factor in bacterial sepsis and many other human diseases.

Anti-Infective and Anti-Inflammatory Mode of Action of Peptide 19-2.5.

The polypeptide Pep19-2.5 (Aspidasept) has been described to act efficiently against infection-inducing bacteria by binding and neutralizing their most potent toxins, i.e.

Encapsulation and release of As pidasept peptides in polysaccharide formulation for oral application.

Due to the increase in bacterial resistance to common antibiotics and the lack of newly approved drugs, antimicrobial peptides (AMP) have been shown to be an alternative to combat infections caused by drug-resistant organisms. In particular, synthetic anti-lipopolysaccharide peptides (SALP) with the lead structure Aspidasept (Pep19-2.5) display a high anti-inflammatory activity in vitro and in vivo systems of endotoxemia and bacteremia.

The Beauty of Asymmetric Membranes: Reconstitution of the Outer Membrane of Gram-Negative Bacteria.

The architecture of the lipid matrix of the outer membrane of Gram-negative bacteria is extremely asymmetric: Whereas the inner leaflet is composed of a phospholipid mixture, the outer leaflet is built up by glycolipids. For most Gram-negative species, these glycolipids are lipopolysaccharides (LPS), for a few species, however, glycosphingolipids. We demonstrate experimental approaches for the reconstitution of these asymmetric membranes as (i) solid supported membranes prepared by the Langmuir-Blodgett technique, (ii) planar lipid bilayers prepared by the Montal-Mueller technique, and (iii) giant unilamellar vesicles (GUVs) prepared by the phase transfer method.

Specific localisation of ions in bacterial membranes unravels physical mechanism of effective bacteria killing by sanitiser.

Antimicrobial resistance is a major threat to public health. Although many commercial sanitisers contain a combination of cationic surfactants and aromatic alcohols, the physical mechanisms where these two substances bind to or how they disturb bacterial membranes are still largely unknown. In this study, we designed a well-defined model of Gram-negative bacteria surfaces based on the monolayer of lipopolysaccharides with uniform saccharide head groups.

Influence of disulfide bonds in human beta defensin-3 on its strain specific activity against Gram-negative bacteria.

Antimicrobial peptides (AMPs) play an important role in the host defense against various microbes. One of the most efficient human AMPs is the human beta defensin-3 (hBD-3) which is produced by, e.g.

Adhesion between P. falciparum infected erythrocytes and human endothelial receptors follows alternative binding dynamics under flow and febrile conditions.

Characterizing the adhesive dynamics of Plasmodium falciparum infected erythrocytes (IEs) to different endothelial cell receptors (ECRs) in flow is a big challenge considering available methods. This study investigated the adhesive dynamics of IEs to five ECRs (CD36, ICAM-1, P-selectin, CD9, CSA) using simulations of in vivo-like flow and febrile conditions. To characterize the interactions between ECRs and knobby and knobless IEs of two laboratory-adapted P.

Comparing Cathelicidin Susceptibility of the Meningitis Pathogens and in Culture Medium in Contrast to Porcine or Human Cerebrospinal Fluid.

Host defense peptides or antimicrobial peptides (AMPs), e.g., cathelicidins, have recently been discussed as a potential new treatment option against bacterial infections.

Inactivation of Bacteria by γ-Irradiation to Investigate the Interaction with Antimicrobial Peptides.

The activity of antimicrobial peptides (AMPs) has been investigated extensively using model membranes composed of phospholipids or lipopolysaccharides in aqueous environments. However, from a biophysical perspective, there is a large scientific interest regarding the direct interaction of membrane-active peptides with whole bacteria. Working with living bacteria limits the usability of experimental setups and the interpretation of the resulting data because of safety risks and the overlap of active and passive effects induced by AMPs.

The C-Terminal VPRTES Tail of LL-37 Influences the Mode of Attachment to a Lipid Bilayer and Antimicrobial Activity.

Cathelicidins are a family of host defense antimicrobial peptides in mammalian species. Among them, LL-37 is the only peptide of this family found in humans. Although LL-37 has been intensively investigated in the past, the mode of exerting its bactericidal activity through the specific interactions with bacterial membranes remains elusive.