Loss of O-Antigen Due to wbbL Mutations is Common and Associated with Increased Mortality in Escherichia coli Bloodstream Infections

Escherichia coli bloodstream infections are common and associated with high mortality. A key feature of E. coli is the lipopolysaccharide (LPS) O-antigen, which contributes to immune evasion during invasive infection. We analyzed serial E. coli isolates from patients with relapsed bacteremia and identified frequent disruption of O-antigen synthesis due to mutations in wbbL, resulting in a rough LPS (R-LPS) phenotype. E. coli with rough LPS isolates were more serum sensitive and less pathogenic in mice. Despite this apparent attenuation, 11 of 66 (18%) E. coli sequence type 131 bloodstream isolates in our cohort lacked O-antigen and were associated with significantly worse clinical outcomes, including septic shock and mortality. Using a recurrent bacteremia model, we show that R-LPS isolates partially evade protective immunity generated against smooth-LPS E. coli, highlighting the importance of host immune context in invasive disease.