Salmonellosis is a common foodborne disease caused by bacteria. The emergence of multidrug-resistant (MDR) Salmonella serotypes, such as Typhimurium, and Salmonella's ability to form biofilms contribute to their resistance and persistence in host and non-host environments. New strategies are needed to treat or prevent Salmonella infections.
View Article and Find Full Text PDFStructure-activity relationship studies of 2,8-disubstituted-1,5-naphthyridines, previously reported as potent inhibitors of () phosphatidylinositol-4-kinase β (PI4K), identified 1,5-naphthyridines with basic groups at 8-position, which retained PI4K inhibitory activity but switched primary mode of action to the host hemoglobin degradation pathway through inhibition of hemozoin formation. These compounds showed minimal off-target inhibitory activity against the human phosphoinositide kinases and MINK1 and MAP4K kinases, which were associated with the teratogenicity and testicular toxicity observed in rats for the PI4K inhibitor clinical candidate MMV390048. A representative compound from the series retained activity against field isolates and lab-raised drug-resistant strains of .
View Article and Find Full Text PDFUnlabelled: Circulating sexual stages of can be transmitted from humans to mosquitoes, thereby furthering the spread of malaria in the population. It is well established that antibodies (Abs) can efficiently block parasite transmission. In search for naturally acquired Ab targets on sexual stages, we established an efficient method for target-agnostic single B cell activation followed by high-throughput selection of human monoclonal antibodies (mAbs) reactive to sexual stages of in the form of gamete and gametocyte extract.
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