Core Oligosaccharide Portion of Lipopolysaccharide Plays Important Roles in Multiple Antibiotic Resistance in...

Gram-negative bacteria are intrinsically resistant to antibiotics due to the presence of the cell envelope, but the mechanisms of this resistance are still not fully understood. In this study, a series of mutants that lack one or more major components associated with the cell envelope were constructed from Escherichia coli K-12 W3110. WJW02 can only synthesize Kdo₂-lipid A, which lacks the core oligosaccharide portion of lipopolysaccharide (LPS). WJW04, WJW07, and WJW08 were constructed from WJW02 by deleting the gene clusters relevant to the biosynthesis of exopolysaccharide, flagella, and fimbriae, respectively. WJW09, WJW010, and WJW011 cells cannot synthesize exopolysaccharide (EPS), flagella, and fimbria, respectively. Compared to the wild type (W3110), mutants WJW02, WJW04, WJW07, and WJW08 cells showed decreased resistance to more than 10 different antibacterial drugs, but the mutants WJW09, WJW010, and WJW011 did not. This indicates that the core oligosaccharide portion of lipopolysaccharide plays an important role in multiple antibiotic resistance in E. coli and that the first heptose in the core oligosaccharide portion is critical. Furthermore, the removal of the core oligosaccharide of LPS leads to influences on cell wall morphology, cell phenotypes, porins, efflux systems, and response behaviors to antibiotic stimulation. The results demonstrate the important role of lipopolysaccharide in the antibiotic resistance of Gram-negative bacteria.