Document Type

Article

Publication Date

5-2026

Identifier

DOI: 10.1038/s41586-026-10225-z; PMCID: PMC13108393

Abstract

Escherichia coli is a leading cause of neonatal sepsis, with infection occurring in approximately one in every 1,000 live births. However, with E. coli colonization beginning soon after birth and defects in neonatal host defence maturation, an alternative consideration is why infection does not occur even more frequently. Here we show that newborn babies with E. coli sepsis have selectively reduced vertically transferred natural antibodies that recognize E. coli, mechanistically explaining their susceptibility to infection. Complementary preclinical studies show that preconceptual intestinal colonization with probiotic E. coli Nissle 1917 (EcN) primes anti-E. coli immunoglobulin G (IgG) antibodies with broad cross-reactivity to clinical isolates responsible for neonatal sepsis that override the inherent susceptibility of neonatal mice. Outer membrane protein A (OmpA) is a target of maternal IgG and is also essential for EcN colonization-induced serological immunogenicity. Upon vertical transfer to neonates, colonization-primed anti-E. coli IgG uniquely protects against infection via opsonization, requiring both complement and IgG Fc receptors. Compared with specimens from sex and gestational age-matched healthy control babies without infection, dried blood spot specimens collected one day after birth from 100 babies with E. coli sepsis show consistently reduced IgG titres to pooled E. coli clinical isolates and OmpA, along with impaired IgG-dependent antibacterial opsonization. Together, these results demonstrate that natural infection susceptibility of neonates is efficiently rescued by anti-E. coli IgG and identify defects in pathogen-targeted vertically transferred immunity as a primary risk factor for severe invasive infection in newborn babies.

Journal Title

Nature

Volume

653

Issue

8114

First Page

519

Last Page

527

MeSH Keywords

Female; Infant, Newborn; Escherichia coli Infections; Escherichia coli; Immunoglobulin G; Mice; Animals; Humans; Male; Neonatal Sepsis; Immunity, Maternally-Acquired; Bacterial Outer Membrane Proteins; Antibodies, Bacterial; Opsonization; Pregnancy; Cross Reactions; Sepsis; Animals, Newborn; Probiotics; Receptors, Fc

PubMed ID

41813901

Keywords

Escherichia coli Infections; Escherichia coli; Immunoglobulin G; Neonatal Sepsis; Maternally-Acquired Immunity; Bacterial Outer Membrane Proteins; Bacterial Antibodies; Opsonization; Pregnancy; Cross Reactions; Sepsis; Probiotics; Fc Receptors

Comments

Grants and funding

This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Publisher's Link: https://www.nature.com/articles/s41586-026-10225-z

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