Department of Plant & Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
Cell Rep. 2022 May 31;39(9):110888. doi: 10.1016/j.celrep.2022.110888.
Lipid A, the membrane-anchored portion of lipopolysaccharide (LPS), is an essential component of the outer membrane (OM) of nearly all Gram-negative bacteria. Here we identify regulatory and structural factors that together render lipid A nonessential in Caulobacter crescentus. Mutations in the ferric uptake regulator fur allow Caulobacter to survive in the absence of either LpxC, which catalyzes an early step of lipid A synthesis, or CtpA, a tyrosine phosphatase homolog we find is needed for wild-type lipid A structure and abundance. Alterations in Fur-regulated processes, rather than iron status per se, underlie the ability to survive when lipid A synthesis is blocked. Fitness of lipid A-deficient Caulobacter requires an anionic sphingolipid, ceramide phosphoglycerate (CPG), which also mediates sensitivity to the antibiotic colistin. Our results demonstrate that, in an altered regulatory landscape, anionic sphingolipids can support the integrity of a lipid A-deficient OM.
脂质 A 是脂多糖（LPS）的膜锚定部分，是几乎所有革兰氏阴性菌外膜（OM）的必需组成部分。在这里，我们确定了调节因子和结构因子，它们共同使脂质 A 在新月柄杆菌中变得非必需。铁摄取调节剂 fur 的突变使新月柄杆菌能够在没有催化脂质 A 合成早期步骤的 LpxC 或我们发现的酪氨酸磷酸酶同源物 CtpA 的情况下存活，后者对于野生型脂质 A 结构和丰度是必需的。当脂质 A 合成受阻时，能够存活的原因是 Fur 调节过程的改变，而不是铁状态本身。脂质 A 缺乏的新月柄杆菌的适应性需要阴离子神经鞘脂，即神经酰胺磷酸甘油（CPG），它也介导对抗生素粘菌素的敏感性。我们的结果表明，在改变的调节环境中，阴离子神经鞘脂可以支持缺乏脂质 A 的 OM 的完整性。
