Anti-Biotin monoclonal antibody, clone DVP.6

Many members of nontuberculous mycobacteria (NTM) are opportunistic pathogens causing several infections in animals. The incidence of NTM infections and emergence of drug-resistant NTM strains are rising worldwide, emphasizing the need to develop novel anti-NTM drugs. The present study is aimed to identify broad-spectrum drug targets in NTM using a comparative genomics approach. The study identified 537 core proteins in NTM of which 45 were pathogen specific and essential for the survival of pathogens. Furthermore, druggability analysis indicated that 15 were druggable among those 45 proteins. These 15 proteins, which were core proteins, pathogen-specific, essential, and druggable, were considered as potential broad-spectrum candidates. Based on their locations in cytoplasm and membrane, targets were classified as drug and vaccine targets. The identified 15 targets were different enzymes, carrier proteins, transcriptional regulator, two-component system protein, ribosomal, and binding proteins. The identified targets could further be utilized by researchers to design inhibitors for the discovery of antimicrobial agents.

Background: The distinctive molecular structure of the prion protein, PrPsc, is established only in mammals with infectious prion diseases. Prion protein characterizes either the transmissible pathogen itself or a primary constituent of the disease. Our report suggested that prion protein-mediated neuronal cell death is triggered by the autophagy flux. However, the alteration of intracellular calcium levels, AMPK activity in prion models has not been described. This study is focused on the effect of the changes in intracellular calcium levels on AMPK/autophagy flux pathway and PrP (106-126)-induced neurotoxicity. Methods: Western blot and Immunocytochemistry was used to detect AMPK and autophagy-related protein expression. Flow cytometry and a TdT-mediated biotin-16-dUTP nick-end labeling (TUNEL) assay were used to detect the percentage of apoptotic cells. Calcium measurement was employed using fluo-4 by confocal microscope. Results: We examined the effect of calcium homeostasis alterations induced by human prion peptide on the autophagy flux in neuronal cells. Treatment with human prion peptide increased the intracellular calcium concentration and induced cell death in primary neurons as well as in a neuronal cell line. Using pharmacological inhibitors, we showed that the L-type calcium channel is involved in the cellular entry of calcium ions. Inhibition of calcium uptake prevented autophagic cell death and reduction in AMP-activated protein kinase (AMPK) activity induced by human prion peptide. Conclusion: Our data demonstrated that prion peptide-mediated calcium inflow plays a pivotal role in prion peptide-induced autophagic cell death, and reduction in AMPK activity in neurons. Altogether, our results suggest that calcium influx might play a critical role in neurodegenerative diseases, including prion diseases.