Phthiocerol dimycocerosate (PDIM) is an essential virulence lipid of Mycobacterium tuberculosis. In vitro culturing rapidly selects for spontaneous PDIM-negative mutants that have attenuated virulence and increased cell wall permeability, thus impacting the relevance of experimental findings. PDIM loss can also reduce the efficacy of the BCG Pasteur vaccine.
View Article and Find Full Text PDFPhthiocerol dimycocerosate (PDIM) is an essential virulence lipid of . culturing rapidly selects for spontaneous mutations that cause PDIM loss leading to virulence attenuation and increased cell wall permeability. We discovered that PDIM loss is due to a metabolic deficiency of methylmalonyl-CoA that impedes the growth of PDIM-producing bacilli.
View Article and Find Full Text PDFFront Cell Infect Microbiol
June 2021
Development of novel anti-tuberculosis combination regimens that increase efficacy and reduce treatment timelines will improve patient compliance, limit side-effects, reduce costs, and enhance cure rates. Such advancements would significantly improve the global TB burden and reduce drug resistance acquisition. Bioenergetics has received considerable attention in recent years as a fertile area for anti-tuberculosis drug discovery.
View Article and Find Full Text PDFAs breakthrough cellular therapy discoveries are translated into reliable, commercializable applications, effective stem cell biomanufacturing requires systematically developing and optimizing bioprocess design and operation. This article proposes a rigorous computational framework for stem cell biomanufacturing under uncertainty. Our mathematical tool kit incorporates: high-fidelity modeling, single variate and multivariate sensitivity analysis, global topological superstructure optimization, and robust optimization.
View Article and Find Full Text PDFExcess phosphorus (P) in aquaculture feeds contributes to the eutrophication of natural waters. While commercially available low-P (LP) fish feeds have been developed, there is uncertainty about their potential to reduce effluent P while maintaining fish growth relative to regular P (RP) feeds. We therefore simulated commercial aquaculture conditions and fed for 55 days rainbow trout (approximately 190 kg/raceway, n = 3 raceways/diet) RP (1.
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