Kloser A, Laird M, Deng M, Misra R
S.C. Johnson Medical Research Center, Mayo Clinic, Scottsdale, AZ, USA.
Mol Microbiol. 1998 Mar;27(5):1003-8. doi: 10.1046/j.1365-2958.1998.00746.x.
The assembly defect of a mutant outer membrane protein, OmpF315, can be corrected by suppressor mutations that lower lipopolysaccharide (LPS) levels and indirectly elevate phospholipid levels. One such assembly suppressor mutation, asmB1, is an allele of lpxC (envA) whose product catalyses the first rate-limiting step in the lipid A (LPS) biosynthesis pathway. Besides reducing LPS levels, asmB1 confers sensitivity to MacConkey medium. A mutation, sabA1, that reverses the MacConkey sensitivity phenotype of asmB1 maps within fabZ (whose product is needed for phospholipid synthesis from a precursor) is also required for lipid A synthesis. In addition to reversing MacConkey sensitivity, the sabA1 mutation reverses the OmpF315 assembly suppression phenotype of asmB1. These results show that OmpF315 assembly suppression by asmB1, which is achieved by lowering LPS levels, can be averted by a subsequent aberration in phospholipid synthesis at a point where the biosynthetic pathways for these two lipid molecules split. OmpF315 assembly suppression can also be achieved in an asmB+ background where FabZ expression is increased. The data obtained in this study provide genetic evidence that elevated phospholipid levels and/or phospholipid to LPS ratios are necessary for assembly suppression.
突变型外膜蛋白OmpF315的组装缺陷可通过抑制突变来纠正，这些抑制突变会降低脂多糖（LPS）水平并间接提高磷脂水平。其中一个组装抑制突变asmB1是lpxC（envA）的一个等位基因，其产物催化脂质A（LPS）生物合成途径中的第一个限速步骤。除了降低LPS水平外，asmB1还使细胞对麦康凯培养基敏感。一个能逆转asmB1的麦康凯敏感性表型的突变sabA1定位于fabZ内（脂质A合成也需要其产物从一个前体合成磷脂）。除了逆转麦康凯敏感性外，sabA1突变还逆转了asmB1的OmpF315组装抑制表型。这些结果表明，由asmB1通过降低LPS水平实现的OmpF315组装抑制，可被这两种脂质分子生物合成途径分支处磷脂合成的后续异常所避免。在asmB+背景中增加FabZ表达也可实现OmpF315组装抑制。本研究获得的数据提供了遗传学证据，表明升高的磷脂水平和/或磷脂与LPS的比例对于组装抑制是必要的。
