Photo Credit: March of Dimes
Scientific Frontline: Extended "At a Glance" Summary: Preventing Neonatal E. coli Sepsis
The Core Concept: Newborn babies who develop sepsis from E. coli bacteria suffer from a critical deficiency in specific maternally transferred antibodies that target a major surface protein common to all E. coli strains.
Key Distinction/Mechanism: While healthy babies are protected against bacterial pathogens via the natural transfer of bacteria-fighting antibodies from mothers during pregnancy, infants who develop neonatal sepsis exhibit a severe, more than 10-fold reduction in E. coli-specific antibodies. This lack of natural immunity is what allows the bacteria to rapidly spread through the blood and overwhelm the body.
Major Frameworks/Components:
- Neonatal Antibody Analysis: The study analyzed blood collected from 100 newborn babies diagnosed with E. coli sepsis to quantitatively measure specific antibody levels.
- Maternal-Fetal Immunity Transfer: Investigates the biological mechanisms of how protective immunoglobulins are naturally transferred from expectant mothers to fetuses.
- Probiotic Colonization Model: Experimental testing utilizing E. coli strain Nissle 1917 (commercially available as Mutaflor) to safely colonize the maternal intestinal tract and stimulate natural antibody production.
Branch of Science: Immunology, Neonatology, Microbiology, and Molecular Biology.
Future Application: Clinical applications derived from this research include prenatal screening protocols to identify high-risk infants by measuring pregnant women's E. coli-specific antibody levels. Additional therapeutic applications include the preventative administration of targeted probiotics (like E. coli strain Nissle 1917) to pregnant women to generate natural antibodies, and treating actively septic infants with immunoglobulins enriched with anti-E. coli antibodies.
Why It Matters: E. coli is a leading cause of neonatal sepsis, affecting approximately 1 in every 1,000 babies, and many strains possess high antibiotic resistance. Filling this critical knowledge gap shifts the clinical focus from reactive antibiotic treatments to proactive immunological detection and prevention, offering a major advancement in preventing life-threatening infections, mitigating antibiotic resistance, and saving newborn lives.
Researchers investigating why some newborn babies contract sepsis, say pregnant women could take a probiotic or be screened for specific antibodies to prevent the life-threatening infection.
An international research collaborative study involving The University of Queensland has discovered babies who develop sepsis lack antibodies targeting E. coli bacteria.
Professor Mark Schembri from UQ’s Institute for Molecular Bioscience said the team, led by the Cincinnati Children's Hospital Medical Center, examined blood collected from 100 newborn babies with E. coli sepsis to measure their antibody levels.
“Despite decades of research it was still not fully understood why E. coli caused sepsis in some babies but not others,’’ Professor Schembri said.
“We showed healthy babies possess protective antibodies against a major surface protein found in all E. coli.
“Conversely, babies that suffered sepsis had significantly reduced E. coli-specific antibodies with more than a 10-fold reduction.
“Our findings offer exciting opportunities to detect or prevent sepsis in newborn babies.’’
Sepsis is a deadly infection where bacteria spreads rapidly through the blood and overwhelms the body.
E. coli is a leading cause of neonatal sepsis, affecting approximately 1 in every 1000 babies.
While many types of E. coli live harmlessly in the gut, some strains are resistant to almost all antibiotics, making it one of the world’s most dangerous bacterial pathogens.
Senior author Professor Sing Sing Way from Cincinnati Children's Hospital Medical Center said the natural transfer of bacteria-fighting antibodies in pregnancy from mothers to babies protected most babies against infection.
“In the rare situation when these antibodies are low in mothers or inefficiently transferred, babies are at much higher risk for infection,” he said.
“Our research shows steps to prevent sepsis could include screening of pregnant women for E. coli-specific antibodies to allow early identification of high-risk infants.”
Professor Schembri said other approaches could include giving a probiotic called E. coli strain Nissle 1917 – sold for human use under the trade name Mutaflor – to pregnant women.
"Our testing in experimental models suggests this would be a safe preventive measure to colonize the intestinal tract of expectant mothers and generate natural maternal antibodies that could protect their babies at birth,” Professor Schembri said.
“These approaches to encourage E. coli-specific antibodies in newborn infants would save lives.’’
Professor Schembri said treatment of sepsis could include administering immunoglobulin enriched with anti-E. coli antibodies.
“Filling this critical knowledge gap is essential to developing better treatments, preventing infections, slowing the rise of antibiotic resistance, and ultimately saving lives,’’ he said.
Collaboration and acknowledgements: Professor Schembri is a co-affiliate of UQ’s School of Chemistry & Molecular Biosciences. The study was led by the Cincinnati Children's Hospital Medical Center and involved researchers at The University of Queensland, the University of Texas Southwestern Medical Center, the Children’s Mercy Hospital Kansas City and the University of Missouri Kansas City.
Funding: The research was funded by grants from the National Institute of Allergy and Infectious Diseases, the Good Ventures Foundation, the Burroughs Wellcome Fund, the March of Dimes Ohio Prematurity Research Collaborative, and the Australian National Health and Medical Research Council.
Published in journal: Nature
Title: Natural maternal immunity protects neonates from Escherichia coli sepsis
Authors: Raymond E. Diep, Ujjwal Adhikari, Kubra Gokce Tezel, Giang Pham, Allison R. Burrell, Mary A. Staat, Nguyen Thi Khanh Nhu, Minh-Duy Phan, Kate M. Peters, Mark A. Schembri, Scott H. Saunders, David B. Haslam, John J. Erickson, Susana Chavez-Bueno, and Sing Sing Way
Source/Credit: University of Queensland
Reference Number: imgy031226_01
.jpg)