Total Synthesis and Structural Reassignment of the Antitubercular Natural Product Evybactin.

The escalating threat posed by antibiotic resistance is a global concern and underscores the need for new antibiotics. In this context, the recent discovery of evybactin, a nonribosomal depsipeptide antibiotic that selectively and potently inhibits the growth of M. tuberculosis, is particularly noteworthy.

Evybactin is a DNA gyrase inhibitor that selectively kills Mycobacterium tuberculosis.

The antimicrobial resistance crisis requires the introduction of novel antibiotics. The use of conventional broad-spectrum compounds selects for resistance in off-target pathogens and harms the microbiome. This is especially true for Mycobacterium tuberculosis, where treatment requires a 6-month course of antibiotics.

[Non-cholera Vibrio species - currently still rare but growing danger of infection in the North Sea and the Baltic Sea].

Background: The abundance of non-cholera Vibrio spp. in the aquatic environment shows a positive correlation with water temperatures. Therefore, climate change has an important impact on the epidemiology of human infections with these pathogens.

Synthesis and antimicrobial evaluation of new nitric oxide-donating fluoroquinolone/oxime hybrids.

A new series of nitric oxide-donating fluoroquinolone/oximes was prepared in this study. The nitric oxide release from the prepared compounds was measured using a modified Griess colorimetric method. The antitubercular evaluation of the synthesized compounds indicated that ketone derivatives 2b and 2e and oximes 3b and 3d exhibited somewhat higher activity than their respective parent fluoroquinolones.

[Vibrio vulnificus, an increasing threat of sepsis in Germany?].

Background: The prevalence of Vibrio vulnificus heavily depends on the temperature and salinity of the sea water. In the course of climate change an increase in cases of fatal sepsis caused by V. vulnificus at the German Baltic Sea coast could be detected.

Design, synthesis and molecular docking of new N-4-piperazinyl ciprofloxacin-triazole hybrids with potential antimicrobial activity.

New N-4-piperazinyl ciprofloxacin-triazole hybrids 6a-o were prepared and characterized. The in vitro antimycobacterial activity revealed that compound 6a experienced promising antimycobacterial activity against Mycobactrium smegmatis compared with the reference isoniazide (INH). Additionally, compound 6a exhibited broad spectrum antibacterial activity against all the tested strains either Gram-positive or Gram-negative bacteria compared with the reference ciprofloxacin.

Long term development of Bathing Water Quality at the German Baltic coast: spatial patterns, problems and model simulations.

Bathing water quality plays a key role for public health, is highly important for recreational tourism and therefore monitored in the EU-Directive 2006/7/EC. To identify pollution hot spots, sources and impacts of the directive-change in 2006, including a change of indicator organisms, we evaluated monitoring data of the past 15 years, collected own data, determined survival rates of indicator organisms and applied hydrodynamic modelling in a micro-tidal-system. Due to higher survival rates under turbid conditions and restricted water exchange, shallow, eutrophic bays and lagoons are hot spots of microbial pollution.

The role of ATP-dependent machines in regulating genome topology.

All cells must copy and express genes in accord with internal and external cues. The proper timing and response of such events relies on the active control of higher-order genomic organization. Cells use ATP-dependent molecular machines to alter the local and global topology of DNA so as to promote and counteract the persistent effects of transcription and replication.

Formation of a Trimeric Xpo1-Ran[GTP]-Ded1 Exportin Complex Modulates ATPase and Helicase Activities of Ded1.

The DEAD-box RNA helicase Ded1, which is essential in yeast and known as DDX3 in humans, shuttles between the nucleus and cytoplasm and takes part in several basic processes including RNA processing and translation. A key interacting partner of Ded1 is the exportin Xpo1, which together with the GTP-bound state of the small GTPase Ran, facilitates unidirectional transport of Ded1 out of the nucleus. Here we demonstrate that Xpo1 and Ran[GTP] together reduce the RNA-stimulated ATPase and helicase activities of Ded1.

VibrioBase: A MALDI-TOF MS database for fast identification of Vibrio spp. that are potentially pathogenic in humans.

Mesophilic marine bacteria of the family Vibrionaceae, specifically V. cholerae, V. parahaemolyticus and V.

Genotypic diversity and virulence characteristics of clinical and environmental Vibrio vulnificus isolates from the Baltic Sea region.

The genetic diversity of Vibrio vulnificus isolates from clinical and environmental sources originating from the Baltic Sea region was evaluated by multilocus sequence typing (MLST), and possible relationships between MLST clusters, potential genotypic and phenotypic traits associated with pathogenicity, and source of isolation were investigated. The studied traits included genotyping of polymorphic loci (16S rRNA, vcg, and pilF), presence/absence of potential virulence genes, including nanA, nab, and genes of pathogenicity regions, metabolic features, hemolytic activity, resistance to human serum, and cytotoxicity to human intestinal cells. MLST generated 35 (27 new) sequence types and divided the 53 isolates (including four reference strains) into two main clusters, with cluster I containing biotype 1 and 2 isolates of mainly environmental origin and cluster II containing biotype 1 isolates of mainly clinical origin.

Structural insights into regulation and action of SWI2/SNF2 ATPases.

This review focuses on recent structural insights into regulation and nucleic acid binding of Superfamily 2 (SF2)-type helicases as they relate to chromatin remodelers. We review structural features of the Chd1 chromatin remodeler regarding regulation of the ATPase motor, and discuss related strategies observed for other SF2 ATPases. Since no SWI2/SNF2 ATPases have yet been captured bound to DNA in a state competent for ATP hydrolysis, we turn to structural examples from the DEAD-box RNA helicase family, and suggest that SWI2/SNF2-specific inserts may be poised to alter canonical duplex DNA structure.

[Knowledge of school pupils about the HIV/AIDS topic at selected schools in Mecklenburg-Western Pomerania].

Aim Of The Study: The increasing numbers of new HIV diagnoses in Germany generate a need to measure the level of knowledge of the young generation about the issue of HIV/AIDS.

Methodology: A survey was conducted of 769 pupils of different age groups and from different schools in Mecklenburg-Western Pomerania. Data analysis was performed using SPSS; statistically significant differences (p<0.

The mode of Hedgehog binding to Ihog homologues is not conserved across different phyla.

Hedgehog (Hh) proteins specify tissue pattern in metazoan embryos by forming gradients that emanate from discrete sites of expression and elicit concentration-dependent cellular differentiation or proliferation responses. Cellular responses to Hh and the movement of Hh through tissues are both precisely regulated, and abnormal Hh signalling has been implicated in human birth defects and cancer. Hh signalling is mediated by its amino-terminal domain (HhN), which is dually lipidated and secreted as part of a multivalent lipoprotein particle.

Catalytic roles for carbon-oxygen hydrogen bonding in SET domain lysine methyltransferases.

SET domain enzymes represent a distinct family of protein lysine methyltransferases in eukaryotes. Recent studies have yielded significant insights into the structural basis of substrate recognition and the product specificities of these enzymes. However, the mechanism by which SET domain methyltransferases catalyze the transfer of the methyl group from S-adenosyl-L-methionine to the lysine epsilon-amine has remained unresolved.

Structural basis for the methylation site specificity of SET7/9.

Human SET7/9 is a protein lysine methyltransferase (PKMT) that methylates histone H3, the tumor suppressor p53 and the TBP-associated factor TAF10. To elucidate the determinants of its substrate specificity, we have solved the enzyme's structure bound to a TAF10 peptide and examined its ability to methylate histone H3, TAF10 and p53 substrates bearing either mutations or covalent modifications within their respective methylation sites. Collectively, our data reveal that SET7/9 recognizes a conserved K/R-S/T/A motif preceding the lysine substrate and has a propensity to bind aspartates and asparagines on the C-terminal side of the lysine target.