Using the neonatal mouse model to investigate dose response and host susceptibility to Cronobacter sakazakii infections in premature infants
Richardson, Arena Nauchette
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Cronobacter sakazakii (C. sakazakii) is an opportunistic pathogen that has been isolated from powdered infant formulas and can result in serious illnesses such as bacteremia, septicemia, meningitis and death in at-risk infants who are exposed to reconstituted powdered infant formulas. The purpose of our study was to describe whether neonatal mice are an appropriate animal model for C. sakazakii infection in premature infants and to evaluate the virulence and pathogenicity of C. sakazakii. The objectives were to 1) compare the susceptibilities of three mouse strains to C. sakazakii, 2) compare the virulence of three strains of C. sakazakii in neonatal mice, and 3) compare the susceptibilities of neonatal mice of different ages to C. sakazakii and identify biomarkers of infection. Neonatal mice were administered reconstituted powdered infant formula inoculated with C. sakazakii via oral gavage. On post-treatment day 7, mice were sacrificed, blood samples were collected, and brain, liver, and cecum tissues were excised and prepared for isolation of C. sakazakii. The CD-1 mouse strain was more susceptible than BALB/C or C57BL/6, with the lowest infectious dose and the lowest lethal dose (102 CFU). Two clinical strains (3290 and SK81) and one food isolate (MNW2) of C. sakazakii were tested for virulence in the mouse model. C. sakazakii strain 3290 was significantly more invasive in brains (42.1% of mice) than were strains MNW2 (6.7%) and SK81 (15.9%). Mortality was observed for all strains of C. sakazakii tested, but with a much lower rate than infection. Age of the neonate affects susceptibility to C. sakazakii infection, as C. sakazakii was isolated from brains, livers, and ceca of neonatal mice treated at PND 1.5 and 5.5 but not from those of pups treated at PND 9.5. In conclusion, neonatal mice are susceptible to oral challenge with C. sakazakii. Our findings suggest that invasiveness does not necessarily correlate with mortality among different strains of C. sakazakii, and the clinical isolates (SK81 and 3290) are more virulent than the food isolate (MNW2). Neonatal mice also show a time-dependent susceptibility to C. sakazakii infection with resistance increasing with increasing age.