Submitting/Presenting Author

Charity DunlopFollow

Presenter Status

Student

Abstract Type

Research

Primary Mentor

Dr. Susana Chavez-Bueno, MD

Start Date

3-5-2022 11:30 AM

End Date

3-5-2022 1:30 PM

Presentation Type

Poster Presentation

Description

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 lateonset sepsis. However, the effects of maternal LF administration to prevent neonatal E. coli invasive infection have not been studied.

Objectives/Goal: Our goal was to test the hypothesis that LF pre-treatment of pregnant mice administered prenatally will significantly reduce the bacterial load in their embryos following infection with E. coli.

Methods/Design: Human LF 100 mcg/mL or placebo were administered vaginally to pregnant 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 E. coli K1+ clinical isolate RS218, which was modified by transposon mutagenesis to constitutively express chloramphenicol (Cam) resistance (RS218-CamR) as selection marker. On E18, maternal vaginal fluid samples and embryo tissues were collected to determine bacterial loads by culture on Cam plates.

Results: Vaginal RS218-CamR loads were significantly lower in LF-pretreated mice compared to placebo, 4.9x10^6 CFU/mL vs. 1.7x10^7 CFU/mL, respectively (P< 0.02). 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). Bacteria invaded the brain of 50% (total n=16) of embryos from LF-pretreated dams vs. 100% (n=18) of brains in the placebo-pretreated group (Fisher exact test, P< 0.001).

Conclusions: Prenatal maternal vaginal administration of LF in pregnant mice significantly decreased vaginal bacterial loads of E. coli. Burden of infection in the offspring was significantly reduced. Prenatal LF is a potential preventative intervention against neonatal sepsis and needs further investigation.

MeSH Keywords

Lactoferrin; Escherichia coli Infections; Neonatal Sepsis

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May 3rd, 11:30 AM May 3rd, 1:30 PM

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

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 lateonset sepsis. However, the effects of maternal LF administration to prevent neonatal E. coli invasive infection have not been studied.

Objectives/Goal: Our goal was to test the hypothesis that LF pre-treatment of pregnant mice administered prenatally will significantly reduce the bacterial load in their embryos following infection with E. coli.

Methods/Design: Human LF 100 mcg/mL or placebo were administered vaginally to pregnant 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 E. coli K1+ clinical isolate RS218, which was modified by transposon mutagenesis to constitutively express chloramphenicol (Cam) resistance (RS218-CamR) as selection marker. On E18, maternal vaginal fluid samples and embryo tissues were collected to determine bacterial loads by culture on Cam plates.

Results: Vaginal RS218-CamR loads were significantly lower in LF-pretreated mice compared to placebo, 4.9x10^6 CFU/mL vs. 1.7x10^7 CFU/mL, respectively (P< 0.02). 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). Bacteria invaded the brain of 50% (total n=16) of embryos from LF-pretreated dams vs. 100% (n=18) of brains in the placebo-pretreated group (Fisher exact test, P< 0.001).

Conclusions: Prenatal maternal vaginal administration of LF in pregnant mice significantly decreased vaginal bacterial loads of E. coli. Burden of infection in the offspring was significantly reduced. Prenatal LF is a potential preventative intervention against neonatal sepsis and needs further investigation.