VIABLE GRAM NEGATIVE BACTERIA WITH REDUCED PROTEOLYTIC ACTIVITY LACKING OUTER MEMBRANE AGONISTS OF TLR4/MD-2
    2.
    发明公开
    VIABLE GRAM NEGATIVE BACTERIA WITH REDUCED PROTEOLYTIC ACTIVITY LACKING OUTER MEMBRANE AGONISTS OF TLR4/MD-2 有权
    具有降低的活性蛋白水解LIFE ELIGIBLE革兰氏阴性细菌而不外膜激动剂TLR4 OF / MD-2

    公开(公告)号:EP2753688A1

    公开(公告)日:2014-07-16

    申请号:EP12829962.5

    申请日:2012-09-07

    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.