568 - Maternal Antepartum Administration of Lactoferrin Ameliorates Neonatal Infection by Bacteremia-Producing Escherichia coli in Mice

Poster Number: 568
Publication Number: 568.427

Charity L. Dunlop, University of Missouri-Kansas City School of Medicine, Parker, KS, United States; Rachel Chevalier, Children's Mercy Hospitals and Clinics, Leawood, KS, United States; Norah Almahbub, Children's Mercy Hospitals and Clinics, kansas city, MO, United States; Joshua Wheatley, Children's Mercy Hospitals and Clinics, Olathe, KS, United States; Osaruese C. Osa-Edoh, Children's Mercy Hospitals and Clinics, Kansas City, MO, United States; Susana Chavez-Bueno, Children's Mercy Hospital, ROELAND PARK, KS, United States

Background: E. coli is a major cause of neonatal sepsis. Vaginal pathogenic E. coli strains ascend into the pregnant uterus infecting the offspring of colonized mothers. Lactoferrin (LF) is an antibacterial and immunomodulatory glycoprotein that has been given to preterm newborns to prevent late-onset sepsis. However, the effects of maternal LF administration to prevent neonatal E. coli invasive infection by clinical isolates that produce sepsis and meningitis have not been studied.

Objective: To determine the efficacy of vaginal lactoferrin administered prenatally to pregnant mice to prevent invasive E. coli disease in their embryos.

Design/Methods: Human lactoferrin (LF) 100 mcg/mL or placebo were administered vaginally to pregnant C57/BL6 mice twice daily on E16 and E17. Two hours after the 4th dose on E17, mice were infected vaginally with 1x10^5 colony forming units (CFU) of the archetypal bacteremia/meningitis-producing clinical isolate RS218, which was modified by transposon mutagenesis to constitutively express chloramphenicol (Cam) resistance (RS218-CamR) as selection marker. RS218-CamR showed no growth differences in vitro compared to the wild-type strain. On E18, maternal vaginal fluid samples were obtained, and placentas and embryo tissues were collected after humane euthanasia to determine bacterial loads by culture on Cam plates.

Results: Vaginal RS218-CamR loads were significantly lower in LF-pretreated pregnant mice compared to placebo, 4.9x10^6 CFU/mL vs. 1.7x10^7 CFU/mL, respectively (Welch's t-test P < 0.02). Placental RS218-CamR loads were also lower in LF-pretreated mice compared to placebo, 5.5x10^3 CFU/100 mg (IQR 1.1x10^2-9.6x10^5, n=16) vs. 2.4x10^6 CFU/100 mg (IQR 4.3x10^5-7.6x10^6, n=17), respectively (Mann-Whitney P < 0.001). Bacterial loads in the blood, liver and spleen, and brains of embryos of LF-pretreated dams were significantly lower compared to those of placebo-treated dams (Table). RS218-CamR was found in the brain tissue of 50% (total n=16) of embryos from LF-pretreated dams vs. 100% (n=18) of embryo brain tissue in the placebo-pretreated group (Fisher exact test, P < 0.001).Conclusion(s): Prenatal maternal vaginal administration of LF significantly decreased vaginal bacterial loads of a clinically significant neonatal invasive K1+ E. coli isolate. Placental bacterial loads, and burden of infection in the offspring were also significantly decreased. The mechanisms by which prenatal LF protects newborns from invasive E. coli disease need investigation. Prenatal lactoferrin is a potential preventative intervention against neonatal sepsis.
Table. Bacterial loads in blood, liver/spleen, and brain of embryos of pregnant mice pretreated with lactoferrin (LF) vs. placebo prior to E. coli RS218-CamR infection (Mann-Whitney Rank Sum comparisons).