A landmark study analyzing 46 years of E. coli infections in Dutch newborns reveals that immune system pressure, not antibiotic resistance, is the main force shaping the evolution of these disease-causing strains.

Researchers from Amsterdam UMC and the University of Birmingham (UK) examined genetic material from 1,790 E. coli isolates collected between 1975 and 2021 by the Netherlands Reference Laboratory for Bacterial Meningitis (NRLBM). The study, published in The Lancet Microbe, focused on samples from newborns and infants under one year old with severe bloodstream infections or meningitis. Long-term bacterial collections from newborns are extremely rare, making this 46-year dataset the first and most comprehensive of its kind.

Key findings show that antimicrobial resistance (AMR) played virtually no role in the development of the bacterial population causing these infections, contrasting with trends seen in adult E. coli infections in other countries. Instead, the study suggests that interactions with the human immune system drive which strains become dominant over time.

The research also challenges the long-held belief that K1 capsule strains are the predominant cause of infections in newborns, a view that has shaped vaccine development. In this study, K1-negative strains accounted for nearly half of the cases, indicating that vaccines targeting only K1-positive E. coli strains may only offer limited protection.

Expert insights

‘Our article demonstrates the importance of systematically building bacterial biobanks over long periods,’ says Prof. Nina van Sorge. ‘This provides crucial information about disease processes, AMR development, and vaccination opportunities. The Dutch dataset is internationally relevant, as the Netherlands has one of the lowest rates of antibiotic use in Europe.’

Prof. van Sorge adds, ‘We have biobanks in place for specific pathogens or disease entities. The NRLBM covers many more than this neonatal pathogen, for example, Neisseria meningitidis, pneumococci, and Listeria, and includes samples from all age groups.’

Nina van Sorge is Professor of Translational Microbiology at Amsterdam UMC and head of the Netherlands Reference Laboratory for Bacterial Meningitis. She also serves on the board of the infectious diseases program and leads the host-microbe interactions theme at the Amsterdam Institute for Immunology and Infectious Diseases.

Prof. Alan McNally (University of Birmingham, UK) adds, ‘The results were a big surprise. Over more than 40 years, we saw virtually no influence of antimicrobial resistance in newborns and young children. Instead, frequent changes in key surface structures, like capsules, drive E. coli’s success. This has major implications for treatment and vaccine development in this vulnerable group.’

These findings also have important implications for clinical practice in neonatal care. As Prof. Nina van Sorge explains, ‘Although I am not a clinician, I think we can say that antimicrobial resistance is not a consideration in treating these infections, at least in the Netherlands.’

Professor Alan McNally is Professor of Microbial Evolutionary Genomics at the University of Birmingham and co-leads the Infection and Acute Care research theme at the NIHR Birmingham Biomedical Research Centre.

Prof. Willem van Schaik (University of Birmingham) notes, ‘Our study shows that responsible antibiotic use can maintain a population of antibiotic-sensitive bacteria, making infections easier to treat than those caused by multi-resistant strains.’

By understanding how these bacteria evolve, the researchers hope their findings will support the development of more effective vaccines and better protection for newborns at greatest risk of life-threatening bacterial infections.

Funding

Supported by the Wellcome Antimicrobial and Antimicrobial Resistance Doctoral Training Programme and the NIHR Birmingham Biomedical Research Centre.

For more information contact Nina van Sorge (n.m.vansorge@amsterdamumc.nl) or read the scientific publication in Lancet Microbe below:

Lineage dynamics of invasive Escherichia coli isolates in the Netherlands from 1975 to 2021: a retrospective longitudinal genomic analysis

Abstract

Background

Escherichia coliis a common cause of invasive infections such as bloodstream and cerebrospinal fluid infections in neonates. Strains positive for the K1 capsule are considered the most common cause of such neonatal invasive infections. This assumption of K1 dominance, and indeed the population genomics ofE colicausing invasive infections in general is largely unstudied. We aimed to provide a comprehensive characterisation of this pathogen population using a longitudinal isolate collection.

Methods

In this analysis we report the findings of the SENTINEL study, a longitudinal genomic analysis of 1790 invasiveE coliisolates collected mainly from newborns in the Netherlands between 1975 and 2021 by the Netherlands Reference Laboratory for Bacterial Meningitis, Amsterdam University Medical Centre, Amsterdam, Netherlands. The dataset included all bacterial strains cultured from cerebrospinal fluid or blood in cases of (clinical) bacterial meningitis (1976 to 1980). In 1981 the criteria were expanded to include neonates (aged ≤4 weeks) withE colisepsis, and from July, 2016 all infants younger than 1 year withE colisepsis were included. All isolates were sequenced using either the HiSeq 2500 or HiSeq 4000 platforms (Illumina, San Diego, CA, USA). We confirmed species and identified sequence types (STs), detected antimicrobial resistance genes, virulence genes, and the presence of K1 capsule, and characterised the dynamics of these factors over time.

Findings

Our data show a highly dynamic bacterial population that is entirely unaffected by antimicrobial resistance determinants. Key pathogen population fluctuations include the complete disappearance of the dominant lineage ST567 and the swapping of dominant ST95 clones from a single serotype O18:H7 clone to two distinct serotype O1:H7 clones, with changes in virulence factors including major fimbrial adhesins. These findings, combined with only 58·8% (1053 of 1790) prevalence in K1-expressing isolates in the entire study population, point to host–pathogen interaction and immune selection pressures as key drivers of bacterial population dynamics in this largely antimicrobial-naive population.

Interpretation

Our data show the vital need for ongoing genomic surveillance of microbial pathogen populations to guide appropriate intervention strategies. Additionally, genomic insights of a pathogen population from one specific disease syndrome or patient population cannot always be generalised across other cohorts.

Authors

Ann E Snaith, PhDa,∗
Boas van der Putten, PhDb,c,∗
Wendy Bril-Keijzers, BScb,d
Rebecca J Hall, PhDa
Steven J Dunn, PhDa
Prof Willem van Schaik, PhDa
Prof Nina M van Sorge, PhDb,d
Prof Alan McNally, PhDa

∗ Contributed equally

Affiliations/Collaborating institutions

  1. Institute of Microbiology and Infection, School of Infection, Inflammation, and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK
  2. Department of Medical Microbiology & Infection Prevention, Netherlands Reference Laboratory for Bacterial Meningitis, Amsterdam University Medical Centre, location University of Amsterdam, Amsterdam, Netherlands
  3. National Institute for Public Health and the Environment, Bilthoven, Netherlands
  4. Amsterdam institute for Immunology and Infectious diseases, Infectious diseases, Amsterdam, the Netherlands

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