High yield production process for Shigella outer membrane particles.

摘要: Gram-negative bacteria naturally shed particles that consist of outer membrane lipids, proteins, and soluble periplasmic components. These have been proposed for use as vaccines but the yield has problematic. We developed a high yielding production process genetically derived from human pathogen Shigella sonnei. Yields approximately 100 milligrams membrane-associated proteins per liter fermentation were obtained cultures S. sonnei ΔtolR ΔgalU at optical densities 30–45 in 5 L fermenter. Proteomic analysis purified showed preparation to primarily contain predicted proteins. highly immunogenic mice. The these density cultivation supports feasibility scaling up this approach an affordable manufacturing process. Furthermore, we demonstrate using with other genetic manipulations e.g. abolition O antigen synthesis modification lipopolysaccharide structure order modify immunogenicity or reactogenicity particles. This work provides basis large scale Generalized Modules Membrane Antigens (GMMA) bacteria.