Loss of O-antigen due to <i>wbbL</i> mutations is common and associated with increased mortality in <i>Escherichia coli</i> 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 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.
Authors
- Blake Hanson (ORCID: https://orcid.org/0000-0003-2949-7818)
- Sanjay Khandelwal (ORCID: https://orcid.org/0000-0002-5661-3856)
- Jianping Jiang (ORCID: https://orcid.org/0000-0002-1066-6362)
- César A. Arias (ORCID: https://orcid.org/0000-0001-9054-9774)
- Granger Sutton (ORCID: https://orcid.org/0000-0001-7498-8048)
- Mark D. Adams (ORCID: https://orcid.org/0000-0003-3161-7460)
- Vance G. Fowler (ORCID: https://orcid.org/0000-0002-8048-0897)
- Brian P. Conlon (ORCID: https://orcid.org/0000-0002-2155-8375)
- Kuan‐Yi Lu (ORCID: https://orcid.org/0000-0002-3663-377X)
- Derrick E. Fouts (ORCID: https://orcid.org/0000-0003-4323-7668)
- Joshua B. Parsons (ORCID: https://orcid.org/0000-0002-0589-3587)
- Felicia Ruffin (ORCID: https://orcid.org/0000-0003-2176-6462)
- Thomas H. Clarke (ORCID: https://orcid.org/0000-0002-1916-1029)
- Lauren Brinkac (ORCID: https://orcid.org/0000-0002-7549-7280)
- Joshua T. Thaden (ORCID: https://orcid.org/0000-0002-3250-0697)
- Amanda Z. Velez
- Yazhong Tao
- Kaleb J. Tyson (ORCID: https://orcid.org/0009-0002-7415-2405)
Institutions
- University of North Carolina at Chapel Hill (US)
- Houston Methodist (US)
- J. Craig Venter Institute (US)
- Noblis (US)
- Duke University (US)
- Cornell University (US)
- Methodist Hospital (US)
- Jackson Laboratory (US)
- Duke Medical Center (US)
- Hackensack Meridian Health (US)
- Duke University Hospital (US)
- Center for Discovery (US)
- The University of Texas Health Science Center (US)
- The University of Texas Health Science Center at Houston (US)
Publication Details
- Journal
- Science Advances
- Published
- 2026-07-01
- DOI
- https://doi.org/10.1126/sciadv.aec4661
- Primary Topic
- Escherichia coli research studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health