LPS O-antigen polysaccharide length impacts outer membrane permeability of enteric gram-negative bacteria
Kerrie L May1,2, Tatsuya Akiyama2,3, Bella G Parker1,2
1Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
Mbio
|November 5, 2025
Summary
Reactivating O-antigen synthesis in bacteria compromises the outer membrane barrier, increasing antibiotic susceptibility. Balancing O-antigen length is crucial for both host defense and maintaining bacterial outer membrane integrity.
Area of Science:
- Bacterial cell envelope biogenesis
- Microbial pathogenesis
- Antibiotic resistance mechanisms
Background:
- The gram-negative outer membrane (OM) is a key barrier against antibiotics and host defenses.
- Lipopolysaccharides (LPS) with O-antigen (O-Ag) decorate the OM, shielding bacteria but potentially compromising barrier function.
- Lab-adapted *Escherichia coli* K-12 strains lack O-Ag synthesis, producing a truncated LPS.
Purpose of the Study:
- To investigate the impact of O-antigen synthesis and length on the OM antibiotic barrier.
- To understand the balance between host defense and OM integrity in LPS production.
- To identify benefits of O-Ag-lacking lipooligosaccharide production.
Main Methods:
- Genetic manipulation of O-Ag synthesis in *E. coli* and *Shigella flexneri*.
- Assessment of OM permeability to antibiotics.
- Correlation of O-Ag chain length with antibiotic sensitivity.
Main Results:
- Reactivating O-Ag synthesis in *E. coli* K-12 permeabilizes the OM to antibiotics.
- Increased O-Ag length correlates with heightened antibiotic sensitivity.
- Shortening or removing O-Ag enhances antibiotic resistance in both *E. coli* and *S. flexneri*.
Conclusions:
- OM integrity relies on a balance of LPS forms; this balance is disrupted in *E. coli* K-12.
- Long O-Ag provides host defense but compromises the OM barrier.
- Producing lipooligosaccharide without O-Ag offers an advantage in maintaining OM integrity.
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