Abstract

Preterm birth is a serious global health problem and the leading cause of infant death before 5 years of age. At least 40% of cases are associated with infection. The most common way for pathogens to access the uterine cavity is by ascending from the vagina. Bioluminescent pathogens have revolutionized the understanding of infectious diseases. We hypothesized that bioluminescent Escherichia coli can be used to track and monitor ascending vaginal infections. Two bioluminescent strains were studied: E. coli K12 MG1655-lux, a nonpathogenic laboratory strain, and E. coli K1 A192PP-lux2, a pathogenic strain capable of causing neonatal meningitis and sepsis in neonatal rats. On embryonic day 16, mice received intravaginal E. coli K12, E. coli K1, or phosphate-buffered saline followed by whole-body bioluminescent imaging. In both cases, intravaginal delivery of E. coli K12 or E. coli K1 led to bacterial ascension into the uterine cavity, but only E. coli K1 induced preterm parturition. Intravaginal administration of E. coli K1 significantly reduced the proportion of pups born alive compared with E. coli K12 and phosphate-buffered saline controls. However, in both groups of viable pups born after bacterial inoculation, there was evidence of comparable brain inflammation by postnatal day 6. This study ascribes specific mechanisms by which exposure to intrauterine bacteria leads to premature delivery and neurologic inflammation in neonates.

Highlights

  • Preterm birth is a serious global health problem and the leading cause of infant death before 5 years of age

  • Ascending Vaginal Infection and Preterm Birth Using Bioluminescent Strains of E. coli. It first was assessed whether a nonpathogenic strain of E. coli K12 MG1655 (E. coli K12) was capable of ascending into the nonpregnant and embryonic day 16.5 pregnant uterine cavity after intravaginal infection

  • E. coli K12 traversed the cervical barrier by 6 hours and ascended into the nonpregnant uterine cavity by 18 hours, reaching the top of the uterine horns by 24 hours (Figure 1A)

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Summary

Introduction

Preterm birth is a serious global health problem and the leading cause of infant death before 5 years of age. On embryonic day 16, mice received intravaginal E. coli K12, E. coli K1, or phosphate-buffered saline followed by whole-body bioluminescent imaging In both cases, intravaginal delivery of E. coli K12 or E. coli K1 led to bacterial ascension into the uterine cavity, but only E. coli K1 induced preterm parturition. Preterm birth is a serious obstetric and global health problem It is defined as delivery before 37 weeks’ gestation and it is known to affect approximately 11% of pregnancies worldwide.[1] It is the leading cause of death in infants younger than 5 years of age and it is associated with serious morbidity in the surviving infants.[2,3] The rates of preterm birth have remained stable over the years and this is largely because of a lack of understanding of the mechanisms behind preterm birth as well as the paucity of effective preventive treatments. The presence of certain intrauterine bacteria is associated with

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