Loss of O-antigen due to <i>wbbL</i> mutations is common and associated with increased mortality in <i>Escherichia coli</i> bloodstream infections.

Abstract

<i>Escherichia coli</i> bloodstream infections are common and associated with high mortality. A key feature of <i>E. coli</i> is the lipopolysaccharide (LPS) O-antigen, which contributes to immune evasion during invasive infection. We analyzed serial isolates from patients with relapsed <i>E. coli</i> bacteremia and identified frequent disruption of O-antigen synthesis due to mutations in <i>wbbL</i>, resulting in a rough LPS phenotype. Rough LPS isolates were more serum sensitive and less pathogenic in mice. Despite this apparent attenuation, 11 of 61 (18%) <i>E. coli</i> sequence type 131 bloodstream isolates in our cohort harbored disruptive <i>wbbL</i> mutations and were associated with significantly worse clinical outcomes, including septic shock and mortality. Using a murine model of recurrent bacteremia, we show that rough LPS isolates partially evade protective immunity generated against smooth LPS <i>E. coli</i>, highlighting the importance of host immune context in invasive disease.