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Updated: May 22, 2026
A Controlled Mouse Model for Neonatal Polymicrobial Sepsis
Published on: January 27, 2019
Susceptibility to Cronobacter sakazakii decreases with increasing age in neonatal CD-1 mice
Arena N Richardson1, Elizabeth A Pollak, Denita Williams
1Department of Environmental Health Science, 206 Environmental Health Science Building, University of Georgia, Athens, GA 30602-2102, USA.
Insights
Neonatal mice infected with Cronobacter sakazakii showed age-dependent susceptibility. Resistance increased with age, with younger mice (postnatal days 1.5 and 5.5) experiencing more severe infections and mortality compared to older mice.
Area of Science:
- Microbiology
- Neonatal Immunology
- Infectious Diseases
Background:
- Cronobacter sakazakii in infant formula poses severe infection risks to neonates, including premature and low birth weight infants.
- Infections can lead to septicemia, meningitis, necrotizing enterocolitis, and death, with potential long-term morbidities like developmental delays.
- The age at which infants become less susceptible to Cronobacter infection is not well understood.
Purpose of the Study:
- To investigate the age-dependent susceptibility of neonatal mice to Cronobacter sakazakii infection.
- To determine the impact of postnatal age on the invasion and dissemination of Cronobacter sakazakii in neonatal mice.
Main Methods:
- Timed-pregnant CD-1 mice were used, and their pups were orally gavaged at postnatal days (PNDs) 1.5, 5.5, and 9.5 with varying doses of Cronobacter sakazakii.
- Brains, livers, and ceca were analyzed for pathogen invasion 7 days post-challenge.
- Serum amyloid A was measured as a biomarker, and mortality was recorded.
Main Results:
- Cronobacter sakazakii invasion was significantly age-dependent, with isolation from brains, livers, and ceca in pups treated at PNDs 1.5 and 5.5, but not at PND 9.5.
- Infection at PND 1.5 showed higher brain invasion (22%) compared to liver (14%) and cecum (18%).
- Mortality and detectable serum amyloid A were primarily observed in neonates treated at PND 1.5.
Conclusions:
- Neonatal mice exhibit time-dependent susceptibility to Cronobacter sakazakii infection.
- Resistance to infection increases with postnatal age in mice.
- These findings highlight the critical vulnerability of very young infants to Cronobacter infections and inform risk assessment for powdered infant formula.
Abstract:
Neonatal, premature, or very low birth weight infants fed reconstituted powdered infant formula contaminated with Cronobacter (Enterobacter sakazakii) may develop infections resulting in severe outcomes such as septicemia, necrotizing enterocolitis, meningitis, or death. Infants who recover from infection may have morbidities such as hydrocephalus, mental retardation, or developmental delays. Although increasing age appears to reduce susceptibility to Cronobacter infection, it is not known at what age or why these infants become less susceptible. Our study objectives were to compare the susceptibilities of neonatal mice of different ages to Cronobacter sakazakii infection. Timed-pregnant CD-1 mice were allowed to give birth naturally. Neonatal mice were orally gavaged at postnatal days (PNDs) 1.5, 5.5, and 9.5 with a single dose of vehicle or 10(3), 10(7), or 10(10) CFU/ml C. sakazakii strain MNW2 in reconstituted powdered infant formula. Pups were euthanized 7 days after challenge. Brains, livers, and ceca were excised and analyzed for C. sakazakii invasion, and blood was collected for serum amyloid A analysis as a biomarker of infection. C. sakazakii invasion was age dependent; the pathogen was isolated from brains, livers, and ceca of neonatal mice treated at PNDs 1.5 and 5.5 but not from those of pups treated at PND 9.5. C. sakazakii was more invasive at PND 1.5 in brains than in livers and ceca and was isolated from 22, 14, and 18% of these tissue samples, respectively. Serum amyloid A was detected in only one treated neonate. Mortality was observed only in neonates treated at PND 1.5. In conclusion, neonatal mice had a time-dependent susceptibility to C. sakazakii infection, with resistance increasing with increasing age.
