Susceptibility to Cronobacter sakazakii Decreases with Increasing Age in Neonatal CD-1 Mice

摘要

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-I 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.