Neurodegenerative Disease Treatment Drug PBT2 Breaks Intrinsic Polymyxin Resistance in Gram-Positive Bacteria.

Gram-positive bacteria do not produce lipopolysaccharide as a cell wall component. As such, the polymyxin class of antibiotics, which exert bactericidal activity against Gram-negative pathogens, are ineffective against Gram-positive bacteria. The safe-for-human-use hydroxyquinoline analog ionophore PBT2 has been previously shown to break polymyxin resistance in Gram-negative bacteria, independent of the lipopolysaccharide modification pathways that confer polymyxin resistance.

Discovery of Cofactor Competitive Inhibitors against the Human Methyltransferase Fibrillarin.

Fibrillarin (FBL) is an essential and evolutionarily highly conserved S-adenosyl methionine (SAM) dependent methyltransferase. It is the catalytic component of a multiprotein complex that facilitates 2'--methylation of ribosomal RNAs (rRNAs), a modification essential for accurate and efficient protein synthesis in eukaryotic cells. It was recently established that human FBL (hFBL) is critical for Nipah, Hendra, and respiratory syncytial virus infections.

The impact of the butterfly effect on human parainfluenza virus haemagglutinin-neuraminidase inhibitor design.

Human parainfluenza viruses represent a leading cause of lower respiratory tract disease in children, with currently no available approved drug or vaccine. The viral surface glycoprotein haemagglutinin-neuraminidase (HN) represents an ideal antiviral target. Herein, we describe the first structure-based study on the rearrangement of key active site amino acid residues by an induced opening of the 216-loop, through the accommodation of appropriately functionalised neuraminic acid-based inhibitors.

Saturation transfer difference NMR spectroscopy as a technique to investigate protein-carbohydrate interactions in solution.

Saturation transfer difference (STD) Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful method for studying protein-ligand interactions in solution. The STD NMR method is capable of identifying the binding epitope of a ligand when bound to its receptor protein. Ligand protons that are in close contact with the receptor protein receive a higher degree of saturation, and as a result stronger STD NMR signals can be observed.

Economic and practical challenges to the formulation of vaccines against endemic infectious diseases such as malaria.

Herein, we analyze in general the current vaccine market and identify potential factors driving and modulating supply and demand for vaccines. An emphasis is placed on changes in regulation in the last 20 years which have led to increased indirect costs of production, and which can create a barrier against the timely use of technological advances to reduce direct costs. Other defining industry characteristics, such as firm numbers and sizes, cost and pricing strategies, nature extent and impact of Government involvement and international regulation are noted.

Production of an enterotoxin by a gastro-enteritis-associated Aeromonas strain.

The potential of motile Aeromonas species to cause human gastrointestinal infections has been recognised recently. Considerable worldwide epidemiological, microbiological and clinical investigations have shown that some strains of the different motile aeromonads are of increasing enteropathogenic significance, especially in children, the elderly and in immunocompromised individuals. Some of the diarrhoeal symptoms of Aeromonas-associated gastro-enteritis have been attributed to enterotoxins.