The Dual Mode of Antibacterial Action of the Synthetic Small Molecule DCAP Involves Lipid II Binding.

The synthetic small molecule DCAP is a chemically well-characterized compound with antibiotic activity against Gram-positive and Gram-negative bacteria, including drug-resistant pathogens. Until now, its mechanism of action was proposed to rely exclusively on targeting the bacterial membrane, thereby causing membrane depolarization, and increasing membrane permeability (Eun 2012, 134 (28), 11322-11325; Hurley 2015, 6, 466-471). Here, we show that the antibiotic activity of DCAP results from a dual mode of action that is more targeted and multifaceted than previously anticipated.

Staphylococcus epidermidis bacteriocin A37 kills natural competitors with a unique mechanism of action.

Many bacteria produce antimicrobial compounds such as lantibiotics to gain advantage in the competitive natural environments of microbiomes. Epilancins constitute an until now underexplored family of lantibiotics with an unknown ecological role and unresolved mode of action. We discovered production of an epilancin in the nasal isolate Staphylococcus epidermidis A37.

Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition in .

Sufficient access to transition metals such as iron is essential for bacterial proliferation and their active limitation within host tissues effectively restricts infection. To overcome iron limitation, the invasive pathogen uses the iron-regulated surface determinant (Isd) system to acquire hemoglobin-derived heme. While heme transport over the cell wall is well understood, its transport over the membrane is hardly investigated.

Dual targeting of the class V lanthipeptide antibiotic cacaoidin.

Antibiotic resistance is reaching alarming levels, demanding for the discovery and development of antibiotics with novel chemistry and mechanisms of action. The recently discovered antibiotic cacaoidin combines the characteristic lanthionine residue of lanthipeptides and the linaridin-specific N-terminal dimethylation in an unprecedented N-dimethyl lanthionine ring, being therefore designated as the first class V lanthipeptide (lanthidin). Further notable features include the high D-amino acid content and a unique disaccharide substitution attached to the tyrosine residue.

Inhibition of peptidoglycan synthesis is sufficient for total arrest of staphylococcal cell division.

Bacterial cell wall biosynthesis is the target of many important antibiotics. Its spatiotemporal organization is closely coordinated with cell division. However, the role of peptidoglycan synthesis within cell division is not fully understood.

Quantitative Analysis of Microscopy Data to Evaluate Bacterial Responses to Antibiotic Treatment.

Microscopy is a powerful method to evaluate the direct effects of antibiotic action on the single cell level. As with other methodologies, microscopy data is obtained through sufficient biological and technical replicate experiments, where evaluation of the sample is generally followed over time. Even if a single antibiotic is tested for a defined time, the most certain outcome is large amounts of raw data that requires systematic analysis.

Uncertainties in the reconstruction of nanostructures in EUV scatterometry and grazing incidence small-angle X-ray scattering.

Increasing miniaturization and complexity of nanostructures require innovative metrology solutions with high throughput that can assess complex 3D structures in a non-destructive manner. EUV scatterometry is investigated for the characterization of nanostructured surfaces and compared to grazing-incidence small-angle X-ray scattering (GISAXS). The reconstruction is based on a rigorous simulation using a Maxwell solver based on finite-elements and is statistically validated with a Markov-Chain-Monte-Carlo sampling method.

Line Scan Raman Microspectroscopy for Label-Free Diagnosis of Human Pituitary Biopsies.

Pituitary adenomas are neoplasia of the anterior pituitary gland and can be subdivided into hormone-producing tumors (lactotroph, corticotroph, gonadotroph, somatotroph, thyreotroph or plurihormonal) and hormone-inactive tumors (silent or null cell adenomas) based on their hormonal status. We therefore developed a line scan Raman microspectroscopy (LSRM) system to detect, discriminate and hyperspectrally visualize pituitary gland from pituitary adenomas based on molecular differences. By applying principal component analysis followed by a k-nearest neighbor algorithm, specific hormone states were identified and a clear discrimination between pituitary gland and various adenoma subtypes was achieved.

Response to Comment on "An excess of massive stars in the local 30 Doradus starburst".

Farr and Mandel reanalyze our data, finding initial mass function slopes for high-mass stars in 30 Doradus that agree with our results. However, their reanalysis appears to underpredict the observed number of massive stars. Their technique results in more precise slopes than in our work, strengthening our conclusion that there is an excess of massive stars (>30 solar masses) in 30 Doradus.

An excess of massive stars in the local 30 Doradus starburst.

The 30 Doradus star-forming region in the Large Magellanic Cloud is a nearby analog of large star-formation events in the distant universe. We determined the recent formation history and the initial mass function (IMF) of massive stars in 30 Doradus on the basis of spectroscopic observations of 247 stars more massive than 15 solar masses ([Formula: see text]). The main episode of massive star formation began about 8 million years (My) ago, and the star-formation rate seems to have declined in the last 1 My.

Steam refining as an alternative to steam explosion.

In steam pretreatment the defibration is usually achieved by an explosion at the end of the treatment, but can also be carried out in a subsequent refiner step. A steam explosion and a steam refining unit were compared by using the same raw material and pretreatment conditions, i.e.

Converting Wannier into Frenkel excitons in an inorganic/organic hybrid semiconductor nanostructure.

Electronic coupling between Wannier and Frenkel excitons in an inorganic/organic semiconductor hybrid structure is experimentally observed. Time-resolved photoluminescence and excitation spectroscopy directly demonstrate that electronic excitation energy can be transferred with an efficiency of up to 50% from an inorganic ZnO quantum well to an organic [2,2-p-phenylenebis-(5-phenyloxazol), alpha-sexithiophene] overlayer. The coupling is mediated via dipole-dipole-interaction analog to the Förster transfer in donor-acceptor systems.

The utilization of renewable resources in German industrial production.

Renewable resources will be an increasingly important issue for the chemical industry in the future. In the context of white biotechnology, they represent the intersection point of agriculture and the chemical industry. The scarcity and related increase in the price of fossil resources make renewable resources an interesting alternative.

Bio-assay based on single molecule fluorescence detection in microfluidic channels.

A rapid bioassay is described based on the detection of colocalized fluorescent DNA probes bound to DNA targets in a pressure-driven solution flowing through a planar microfluidic channel. By employing total internal reflection excitation of the fluorescent probes and illumination of almost the entire flow channel, single fluorescent molecules can be efficiently detected leading to the rapid analysis of nearly the entire solution flowed through the device. Cross-correlation between images obtained from two spectrally distinct probes is used to determine the target concentration and efficiently reduces the number of false positives.

A C-terminal translocation signal is necessary, but not sufficient for type IV secretion of the Helicobacter pylori CagA protein.

Type IV secretion systems are increasingly recognized as important virulence determinants of Gram-negative bacterial pathogens. While the examination of several type IV-secreted proteins suggested that their secretion depends on C-terminal signals, the nature of these signals and their conservation among different systems remain unclear. Here, we have characterized the secretion signal of the Helicobacter pylori CagA protein, which is translocated by the Cag type IV secretion apparatus into eucaryotic cells.

Heterologous expression and characterization of a novel branching enzyme from the thermoalkaliphilic anaerobic bacterium Anaerobranca gottschalkii.

The gene encoding the branching enzyme (BE) from the thermoalkaliphilic, anaerobic bacterium Anaerobranca gottschalkii was fused with a twin arginine translocation protein secretory-pathway-dependent signal sequence from Escherichia coli and expressed in Staphylococcus carnosus. The secreted BE was purified using hydrophobic interaction and gel filtration chromatography. The monomeric enzyme (72 kDa) shows maximal activity at 50 degrees C and pH 7.

Regioselective deacetylation of cellulose acetates by acetyl xylan esterases of different CE-families.

Cellulose acetate (CA) was found to be a substrate of several acetyl xylan esterases (AXE). Eight AXE from different carbohydrate esterase (CE) families were tested on their activity against CA with a degree of substitution of 0.7 and 1.

A novel sheathed surface organelle of the Helicobacter pylori cag type IV secretion system.

Type I strains of Helicobacter pylori (Hp) use a type IV secretion system (T4SS), encoded by the cag pathogenicity island (cag-PAI), to deliver the bacterial protein CagA into eukaryotic cells and to induce interleukin-8 secretion. Translocated CagA is activated by tyrosine phosphorylation involving Src-family kinases. The mechanism and structural basis for type IV protein secretion is not well understood.

Laser action of trions in a semiconductor quantum well.

We report on the observation of optical gain and lasing at the trion transition of n-doped ZnSe quantum wells. Specifically, the (stimulated) emission-absorption net rate of this transition is controlled by the difference of trion and electron occupation in momentum space. As the mass of the trion is larger than that of the electron, gain occurs on the low-energy side of the line center without degeneracy and inversion in the total particle numbers.

CagA tyrosine phosphorylation and interleukin-8 induction by Helicobacter pylori are independent from alpAB, HopZ and bab group outer membrane proteins.

In several studies Helicobacter pylori type I strains (cag-positive strains) have been described to translocate their CagA protein into epithelial cells, where it is tyrosine-phosphorylated. The intimate contact allows a Cag-dependent bacteria-to-cell signaling inducing the secretion of the chemokine interleukin-8. Although a contact between the bacterial and the eukaryotic cell is known to be necessary for these signal transduction events the bacterial adhesin and the cellular receptor are unknown, so far.

Reduction of neuronal and inducible nitric oxide synthase gene expression in patients with cystic fibrosis.

As a consequence of diminished nitric oxide synthase (NOS) protein concentration, the airway concentration of nitric oxide (NO) is reduced in patients with cystic fibrosis (CF). This appears to lead to a reduced elimination of such microorganisms as Pseudomonas aeruginosa. The objective of this study was to analyze whether inducible (iNOS), endothelial (eNOS) and neuronal (bNOS) NOS are reduced at mRNA level and if so whether this is caused directly by the defective CF transmembrane conductance regulator (CFTR).

Activation of Helicobacter pylori CagA by tyrosine phosphorylation is essential for dephosphorylation of host cell proteins in gastric epithelial cells.

Helicobacter pylori type I strains harbour the cag pathogenicity island (cag-PAI), a 37 kb sequence,which encodes the components of a type IV secretion system. CagA, the first identified effector protein of the cag-PAI, is translocated into eukaryotic cells and tyrosine phosphorylated (CagAP-tyr) by a host cell tyrosine kinase. Translocation of CagA induces the dephosphorylation of a set of phosphorylated host cell proteins of unknown identity.

Systematic mutagenesis of the Helicobacter pylori cag pathogenicity island: essential genes for CagA translocation in host cells and induction of interleukin-8.

Helicobacter pylori (Hp) carries a type IV secretion system encoded by the cag pathogenicity island (cag-PAI), which is used to: (i) translocate the bacterial effector protein CagA into different types of eukaryotic cells; and (ii) induce the synthesis and secretion of chemokines, such as interleukin-8 (IL-8). The cag-PAI in Hp 26695 consists of 27 putative genes, six of which were identified as homologues to the basic type IV secretion system represented by the Agrobacterium tumefaciens virB operon. To define the role and contribution of each of the 27 genes, we applied a precise deletion/insertion mutagenesis procedure to knock out each individual gene without causing polar effects on the expression of downstream genes.

Investigation on molar mass, solubility and enzymatic fragmentation of xylans by multi-detected SEC chromatography.

Four xylan samples from different origin were investigated, using a multi-detector, size exclusion, chromatographic system with two chromatographic column sets and mobile phases differing in the DMSO:water ratio. Molar mass distribution could be analysed best using a mobile phase of DMSO:water (90:10) with addition of 0.05 M LiBr, a system offering good solubilisation of the polymers and a proper chromatographic separation.