: Since disulfiram's discovery in the 1940s and its FDA approval for alcohol use disorder, other indications have been investigated. This review describes potential clinical applications, associated risks, and challenges. : For this narrative review, a PubMed search was conducted for articles addressing in vivo studies of disulfiram with an emphasis on drug repurposing for the treatment of human diseases.
View Article and Find Full Text PDFLyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the United States alone. The antibiotics currently used to treat Lyme disease are broad spectrum, damage the microbiome, and select for resistance in non-target bacteria.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
April 2018
One of the main differences between bacteria and archaea concerns their membrane composition. Whereas bacterial membranes are made up of glycerol-3-phosphate ester lipids, archaeal membranes are composed of glycerol-1-phosphate ether lipids. Here, we report the construction of a stable hybrid heterochiral membrane through lipid engineering of the bacterium By boosting isoprenoid biosynthesis and heterologous expression of archaeal ether lipid biosynthesis genes, we obtained a viable strain of which the membranes contain archaeal lipids with the expected stereochemistry.
View Article and Find Full Text PDFContext: Osteoporosis is a major cause of morbidity and mortality in both men and women. The mortality rate in men within 1 year of hip fracture is 37.5%, which is 51% higher than in women.
View Article and Find Full Text PDFIn archaea, the membrane phospholipids consist of isoprenoid hydrocarbon chains that are ether-linked to a sn-glycerol1-phosphate backbone. This unique structure is believed to be vital for the adaptation of these micro-organisms to extreme environments, but it also reflects an evolutionary marker that distinguishes archaea from bacteria and eukaryotes. CDP-archaeol is the central precursor for polar head group attachment.
View Article and Find Full Text PDFA vital function of the cell membrane in all living organism is to maintain the membrane permeability barrier and fluidity. The composition of the phospholipid bilayer is distinct in archaea when compared to bacteria and eukarya. In archaea, isoprenoid hydrocarbon side chains are linked via an ether bond to the sn-glycerol-1-phosphate backbone.
View Article and Find Full Text PDFArchaeal membrane lipid composition is distinct from Bacteria and Eukarya, consisting of isoprenoid chains etherified to the glycerol carbons. Biosynthesis of these lipids is poorly understood. Here we identify and characterize the archaeal membrane protein CDP-archaeol synthase (CarS) that catalyzes the transfer of the nucleotide to its specific archaeal lipid substrate, leading to the formation of a CDP-activated precursor (CDP-archaeol) to which polar head groups are attached.
View Article and Find Full Text PDFType IV pili (T4P) are ubiquitous and versatile bacterial cell surface structures involved in adhesion to host cells, biofilm formation, motility, and DNA uptake. In Gram-negative bacteria, T4P pass the outer membrane (OM) through the large, oligomeric, ring-shaped secretin complex. In the β-proteobacterium Neisseria gonorrhoeae, the native PilQ secretin ring embedded in OM sheets is surrounded by an additional peripheral structure, consisting of a peripheral ring and seven extending spikes.
View Article and Find Full Text PDFBackground: Most strains of Neisseria gonorrhoeae carry a Gonococcal Genetic Island which encodes a type IV secretion system involved in the secretion of ssDNA. We characterize the GGI-encoded ssDNA binding protein, SsbB. Close homologs of SsbB are located within a conserved genetic cluster found in genetic islands of different proteobacteria.
View Article and Find Full Text PDFThe type IV secretion system (T4SS) encoded within the gonococcal genetic island (GGI) of Neisseria gonorrhoeae has homology to the T4SS encoded on the F plasmid. The GGI encodes the putative pilin protein TraA and a serine protease TrbI, which is homologous to the TraF protein of the RP4 plasmid involved in circularization of pilin subunits of P-type pili. TraA was processed to a 68-amino acid long circular peptide by leader peptidase and TrbI.
View Article and Find Full Text PDFStructures of the type IV pili secretin complexes from Neisseria gonorrhoeae and Neisseria meningitidis, embedded in outer membranes were investigated by transmission electron microscopy. Single particle averaging revealed additional domains not observed previously. Secretin complexes of N.
View Article and Find Full Text PDFThe Neisseria gonorrhoeae type IV secretion system secretes chromosomal DNA that acts in natural transformation. To examine the mechanism of DNA processing for secretion, we made mutations in the putative relaxase gene traI and used nucleases to characterize the secreted DNA. The nuclease experiments demonstrated that the secreted DNA is single-stranded and blocked at the 5' end.
View Article and Find Full Text PDFBioinformatics tools to aid gene and protein sequence analysis have become an integral part of biology in the post-genomic era. Release of the Plasmodium falciparum genome sequence has allowed biologists to define the gene and the predicted protein content as well as their sequences in the parasite. Using pI and molecular weight as characteristics unique to each protein, we have developed a bioinformatics tool to aid identification of proteins from Plasmodium falciparum.
View Article and Find Full Text PDFJ Assoc Physicians India
June 2005
Aim Of The Study: Microalbuminuria is currently the only diagnostic tool available for early diagnosis of diabetic nephropathy. The test is based on immunological detection of small quantities of albumin in the urinary samples of diabetes patients. There are several limitations of the use of microalbuminuria as an index of renal function.
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