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Copyright © 2026 Walker et al. Uropathogenic Escherichia coli (UPEC) strains that express the K1 capsule are associated with severe invasive disease, including pyelonephritis, urosepsis, and neonatal meningitis. The K1 capsule can be modified by NeuO, a phage-encoded phase-variable O-acetyltransferase. The role of O-acetylation in pathogenesis of K1 UPEC remains to be fully elucidated. Here, we assessed the prevalence of the neuO gene in a K1 E. coli data set comprising 8,659 genomes and observed that 43.5% of genomes harbor neuO, with a high prevalence (88.1%) in the pandemic UPEC clone sequence type (ST) 95. We generated an isogenic ∆neuO mutant in the reference ST95 strain MS7163 and complemented this with a phase-ON locked version of the neuO gene, resulting in constitutive O-acetylation of the K1 capsule. The phase-variable rate of neuO in MS7163 was measured by fragment analysis at 93% phase-ON with 21 heptanucleotide repeats. NeuO acetylated the K1 sialic acid into O-acetylated forms, including Neu5,7Ac2, Neu5,8Ac2, and Neu5,9Ac2. We demonstrate that O-acetylation increased survival of K1 UPEC to lytic K1 phage and human neutrophils, yet increased susceptibility to human serum. O-acetylation of the K1 capsule did not influence bladder colonization in a murine model of urinary tract infection. Overall, we hypothesize that phase-variable O-acetylation is a niche-specific adaptive mechanism that enhances survival of UPEC in different ways, including protection against K1 phage and resistance to neutrophil-mediated killing.
Author(s): Walker LL, Nhu NTK, Lian ZJ, Peters KM, Monteleone M, Connolly JPR, Walker MJ, Forde BM, Schroder K, Sweet MJ, Phan M-D, Schembri MA
Publication type: Article
Publication status: Published
Journal: Journal of Bacteriology
Year: 2026
Volume: 208
Issue: 3
Print publication date: 01/03/2026
Online publication date: 10/02/2026
Acceptance date: 14/01/2026
Date deposited: 07/04/2026
ISSN (print): 0021-9193
ISSN (electronic): 1098-5530
Publisher: American Society for Microbiology
URL: https://doi.org/10.1128/jb.00610-25
DOI: 10.1128/jb.00610-25
PubMed id: 41665341
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