Caulobacter lipid A is conditionally dispensable in the absence of fur and in the presence of anionic sphingolipids

• Published in: Cell reports (Cambridge) 2022-05, Vol.39 (9), p.110888-110888, Article 110888
• Main Authors: Zik, Justin J., Yoon, Sung Hwan, Guan, Ziqiang, Stankeviciute Skidmore, Gabriele, Gudoor, Ridhi R., Davies, Karen M., Deutschbauer, Adam M., Goodlett, David R., Klein, Eric A., Ryan, Kathleen R.
• Format: Article
• Language: English
• Subjects: BASIC BIOLOGICAL SCIENCES; Caulobacter; ceramide; Fur; iron; lipid A; lipopolysaccharide; outer membrane; sphingolipid
• ISSN: 2211-1247; 2211-1247
• 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. [Display omitted] •Lipid A is conditionally essential for viability in Caulobacter crescentus•Inactivation of Fur is required for survival of lipid A-deficient Caulobacter•Anionic sphingolipids promote Caulobacter fitness in the absence of lipid A•Anionic sphingolipids, rather than LPS, underlie colistin sensitivity in Caulobacter Lipid A, the membrane-anchoring segment of lipopolysaccharide, is generally considered to be an essential component of the Gram-negative bacterial outer membrane. Zik et al. show that deletion of the transcriptional regulator fur and synthesis of the anionic sphingolipid ceramide phosphoglycerate enable Caulobacter crescentus to survive without lipid A.