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VIABLE GRAM NEGATIVE BACTERIA WITH REDUCED PROTEOLYTIC ACTIVITY LACKING OUTER MEMBRANE AGONISTS OF TLR4/MD-2
VIABLE GRAM NEGATIVE BACTERIA WITH REDUCED PROTEOLYTIC ACTIVITY LACKING OUTER MEMBRANE AGONISTS OF TLR4/MD-2
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机译:缺乏蛋白水解活性,缺乏外膜激动剂的TLR4 / MD-2的可行革兰氏阴性细菌
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摘要
Viable Gram-negative bacteria or components thereof comprising outer membranes that substantially lack a ligand, such as Lipid A or 6-acyl lipidpolysaccharide, that acts as an agonist of TLR4/MD-2. The bacteria may comprise reduced activity of arabinose-5-phosphate isomerases and one or more suppressor mutations, for example in a transporter thereby increasing the transporter's capacity to transport lipid IVA or in membrane protein YhjD. One or more genes (e.g., lpxL, lpxM, pagP, lpxP, and/or eptA) may be substantially deleted and/or one or more enzymes (e.g., LpxL, LpxM, PagP, LpxP, and/or EptA) may be substantially inactive. The bacteria may be competent to take up extracellular DNA, may be donor bacteria, or may be members of a library. The present invention also features methods of creating and utilizing such bacteria.
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