Ascending Vaginal Infection Using Bioluminescent Bacteria Evokes Intrauterine Inflammation, Preterm Birth, and Neonatal Brain Injury in Pregnant Mice

摘要

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. Supported by the Wellbeing of Women Research training fellowship RT414 and the Priory Foundation (N.S.); UK Medical Research Council grants G1000709 and MR/N026101/1, MR/R015325/1, MR/P026494/1, and MR/N019075/1, and Sport Aiding Medical Research for Kids (SPARKS) 17UCL01 (S.N.W.); MR/P026494/1 and SPARKS 17UCL01 (R.K.); MR/K02342X/1, GOSHCCV1284, and Rosetrees M576 (J.N.); and Research Training Fellowship GN2137 from Action Medical Research. Production of Escherichia coli A192PP- lux2 was funded by Action Medical Research grant GN2075. Disclosures: None declared. ? 2018 American Society for Investigative Pathology. Published by Elsevier Inc. No articles found. Citing articles View article metrics Elsevier About ScienceDirect Remote access Shopping cart Contact and support Terms and conditions Privacy policy We use cookies to help provide and enhance our service and tailor content and ads. By continuing you agree to the use of cookies .Copyright ? 2018 Elsevier B.V. or its licensors or contributors. ScienceDirect ? is a registered trademark of Elsevier B.V. RELX Group.