Loss of O-antigen due to wbbL mutations is common and associated with increased mortality in Escherichia coli bloodstream infections
- Kaleb J. Tyson
- Amanda Z. Velez
- Blake M. Hanson
- Jianping Jiang
- Kuan-Yi Lu
- Felicia Ruffin
- Granger Sutton
- Lauren M. Brinkac
- Thomas H. Clarke
- Yazhong Tao
- Derrick E. Fouts
- Mark D. Adams
- Cesar A. Arias
- Sanjay Khandelwal
- Vance G. Fowler
- Joshua T. Thaden
- Brian P. Conlon
- Joshua B. Parsons
2026-07-01
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 isolates from patients with relapsed E. coli bacteremia and identified frequent disruption of O-antigen synthesis due to mutations in wbbL , 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%) E. coli sequence type 131 bloodstream isolates in our cohort harbored disruptive wbbL 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 E. coli , highlighting the importance of host immune context in invasive disease.