Deletion of the Escherichia coli K30 Group I Capsule Biosynthesis Genes wza, wzb and wzc Confers Capsule-Independent Resistance to Macrolide Antibiotics

The Escherichia coli capsule functions to protect bacterial cells from desiccation and environmental stresses. The E. coli group I capsule is polymerized and transported to the surface of the cells through the action of the wza, wzb and wzc gene products. It is thought that the presence of a capsule may confer a level of intrinsic antibiotic resistance. Previous work exploring the role of capsule in antibiotic resistance showed inconsistent results between different studies, and that the role of capsule in antibiotic resistance may be dependent on antibiotic class. In this study we sought to examine the role of the E. coli K30 group I capsule in antibiotic resistance across ten different antibiotic classes. We examined the E. coli K30 strain CWG655Δ[wza-wzb-wzcK30] that has a chromosomal deletion of three key capsule biosynthesis genes (wza, wzb and wzc) and its isogenic parental strain E69. We quantified the capsule production of both strains and compared the susceptibility of the strains to ten different antibiotics. In doing so, we identified macrolide antibiotics as a class of interest and further examined the susceptibility of the strains to additional macrolides and a ketolide. We observed that CWG655Δ[wza-wzb-wzcK30] exhibited diminished production of capsular polysaccharides compared to E69 at 21°C, but that both strains produced comparably low amounts of capsule at 37°C. Contrary to past work on other antibiotic classes, we observed that CWG655Δ[wza-wzb-wzcK30] was more resistant to macrolide antibiotics, but not ketolides, when compared to E69 at both 21°C and 37°C. From this study, we conclude that a deletion of the capsule biosynthesis genes wza, wzb and wzc confers resistance to the macrolide family of antibiotics in a mechanism independent of capsule production.