Cited by 275Immune Response and InflammationEscherichia coli research studiesImmunotherapy and Immune Responses

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A novel Escherichia coli lipid A mutant that produces an antiinflammatory lipopolysaccharide.

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Somerville, J E, Cassiano, L, Bainbridge, B, Cunningham, M D, Darveau, R P·1996·Journal of Clinical Investigation

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Abstract

A unique screen was used to identify mutations in Escherichia coli lipid A biosynthesis that result in a decreased ability to stimulate E-selectin expression by human endothelial cells. A mutation was identified in the msbB gene of E. coli that resulted in lipopolysaccharide (LPS) that lacks the myristoyl fatty acid moiety of the lipid A. Unlike all previously reported lipid A mutants, the msbB mutant was not conditionally lethal for growth. Viable cells or purified LPS from an msbB mutant had a 1000-10,000-fold reduction in the ability to stimulate E-selectin production by human endothelial cells and TNF alpha production by adherent monocytes. The cloned msbB gene was able to functionally complement the msbB mutant, restoring both the LPS to its native composition and the ability of the strain to stimulate immune cells. Nonmyristoylated LPS acted as an antagonist for E-selectin expression when mixed with LPS obtained from the parental strain. These studies demonstrate a significant role for the myristate component of LPS in immune cell activation and antagonism. In addition, the msbB mutant allowed us to directly examine the crucial role that the lipid A structure plays when viable bacteria are presented to host defense cells.

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Authors: Somerville, J. E., Cassiano, L., Bainbridge, B., Cunningham, M. D., & Darveau, R. P.
Affiliations: Bristol-Myers Squibb (United States) (US)
ORCID: Cassiano, L
Cunningham, M D
Darveau, R P
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1996-01-15
Volume: 97
Issue: 2
Pages: 359-365
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci118423
PMC: PMC507025
OpenAlex: W2006697711
Cited by: 275
References: 31
Citations by year: 2026: 4 · 2025: 5 · 2024: 7 · 2023: 10 · 2022: 8 · 2021: 3 · 2020: 6 · 2019: 5 · 2018: 6 · 2017: 10 · 2016: 5 · 2015: 6 · 2014: 7 · 2013: 11 · 2012: 8
FWCI: 5.07
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Bristol-Myers Squibb
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: Escherichia coli, lipid A, lipopolysaccharide biosynthesis, E-selectin, endothelial cells, TNF-α, monocytes, immune cell activation, complementation
MeSH terms: Acyltransferases, Cells, Cultured, Endothelium, Vascular, Escherichia coli, Fatty Acids, Humans, Isomerases, Lipid A, Lipopolysaccharides, Myristic Acids, Structure-Activity Relationship, Tumor Necrosis Factor-alpha, Mutagenesis, E-Selectin, Protein Disulfide-Isomerases, Myristic Acid, Escherichia coli Proteins

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A novel Escherichia coli lipid A mutant that produces an antiinflammatory lipopolysaccharide.

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