Soluble LPS May be a More Potent Competitive Inhibitor to Polymyxin B Than Escherichia coli O9a:K30 Capsular Polysaccharides

Escherichia coli expresses an extracellular layer of capsular polysaccharide (CPS) that confers protection from environmental stressors such as desiccation and antibiotics. Recent research has suggested a correlation between CPS and resistance to cationic antimicrobial peptides such as Polymyxin B (PmB). It is suggested that CPS acts as a binding target for PmB which prevents interaction with the bacterial surface and hence killing. However, in this model the role of lipopolysaccharide (LPS), the target molecule of PmB, has yet to be assessed. It is known that PmB directly interacts with LPS and inactivates the endotoxin. Similarly, LPS has been shown to interact with PmB. In our study, we investigated the degree to which LPS and CPS neutralize activity of PmB. CPS was extracted and quantified from E69 and the isogenic CPS deficient E. coli strain CWG655Δ[wza-wzb-wzcK30]. The degree to which soluble CPS can confer additional resistance to PmB was assessed by a minimum inhibitory concentration assay in liquid broth culture. Our data suggest that soluble LPS neutralizes the bactericidal
properties of PmB while soluble CPS may not. LPS may be a more potent inhibitor of PmB than CPS.