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

Justin J Zik; Sung Hwan Yoon; Ziqiang Guan; Gabriele Stankeviciute Skidmore; Ridhi R Gudoor; Karen M Davies; Adam M Deutschbauer; David R Goodlett; Eric A Klein; Kathleen R Ryan

doi:10.1016/j.celrep.2022.110888

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

Cell Rep. 2022 May 31;39(9):110888. doi: 10.1016/j.celrep.2022.110888.

Authors

Affiliations

¹ Department of Plant & Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
² Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
³ Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
⁴ Center for Computational and Integrative Biology, Rutgers University-Camden, Camden, NJ 08102, USA; Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08901, USA.
⁵ Molecular Biosciences and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
⁶ Environmental Genomics & Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
⁷ Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA; Department of Biochemistry & Microbiology, University of Victoria, Victoria, BC V8W 2Y2, Canada; University of Victoria-Genome BC Proteomics Centre, Victoria, BC V8Z 7X8, Canada.
⁸ Center for Computational and Integrative Biology, Rutgers University-Camden, Camden, NJ 08102, USA; Biology Department, Rutgers University-Camden, Camden, NJ 08102, USA; Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08901, USA.
⁹ Department of Plant & Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Environmental Genomics & Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: krr@berkeley.edu.

Abstract

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.

Keywords: CP: Microbiology; Caulobacter; Fur; ceramide; iron; lipid A; lipopolysaccharide; outer membrane; sphingolipid.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Caulobacter crescentus* / genetics
Caulobacter*
Lipid A
Lipopolysaccharides
Sphingolipids

Substances

Lipid A
Lipopolysaccharides
Sphingolipids

Abstract

Publication types

MeSH terms

Substances

Grants and funding