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

Journal Article · · Cell Reports
ORCiD logo [1];  [2];  [3];  [4];  [5]; ORCiD logo [5];  [6]; ORCiD logo [7]; ORCiD logo [4]; ORCiD logo [8]
  1. Univ. of California, Berkeley, CA (United States)
  2. University of Maryland School of Dentistry, Baltimore, MD (United States)
  3. Duke University Medical Center, Durham, NC (United States)
  4. Rutgers University, Camden, NJ (United States); Rutgers Univ., New Brunswick, NJ (United States)
  5. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)
  6. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  7. University of Maryland School of Dentistry, Baltimore, MD (United States); Univ. of Victoria, BC (Canada); University of Victoria-Genome BC Proteomics Centre, Victoria, BC (Canada)
  8. Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Science Foundation (NSF); National Institutes of Health (NIH); USDOE Laboratory Directed Research and Development (LDRD) Program
Grant/Contract Number:
AC02-05CH11231; 1553004; 2031948; 1615287; GM111066-01; 1R01AI123820-01
OSTI ID:
1896689
Journal Information:
Cell Reports, Vol. 39, Issue 9; ISSN 2211-1247
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English

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Figures / Tables (7)