Ascending vaginal infection using bioluminescent bacteria evokes intrauterine inflammation, preterm birth, and neonatal brain injury in pregnant mice

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dc.contributor.authorSuff, Natalie
dc.contributor.authorKarda, Rajvinder
dc.contributor.authorDiaz, Juan A.
dc.contributor.authorNg, Joanne
dc.contributor.authorBaruteau, Julien
dc.contributor.authorPerocheau, Dany
dc.contributor.authorTangney, Mark
dc.contributor.authorTaylor, Peter W.
dc.contributor.authorPeebles, Donald
dc.contributor.authorBuckley, Suzanne M. K.
dc.contributor.authorWaddington, Simon N.
dc.date.accessioned2019-10-01T05:10:39Z
dc.date.available2019-10-01T05:10:39Z
dc.date.issued2018-10-10
dc.description.abstractPreterm 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.en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationSuff, N., Karda, R., Diaz, J.A., Ng, J., Baruteau, J., Perocheau, D., Tangney, M., Taylor, P.W., Peebles, D., Buckley, S.M. and Waddington, S.N., 2018. Ascending Vaginal Infection Using Bioluminescent Bacteria Evokes Intrauterine Inflammation, Preterm Birth, and Neonatal Brain Injury in Pregnant Mice. The American journal of pathology, 188(10), (13pp). DOI:10.1016/j.ajpath.2018.06.016en
dc.identifier.doi10.1016/j.ajpath.2018.06.016en
dc.identifier.eissn1525-2191
dc.identifier.endpage2176en
dc.identifier.issn0002-9440
dc.identifier.issued10en
dc.identifier.journaltitleAmerican Journal of Pathologyen
dc.identifier.startpage2164en
dc.identifier.urihttps://hdl.handle.net/10468/8643
dc.identifier.volume188en
dc.language.isoenen
dc.publisherElsevier Inc.en
dc.relation.urihttp://www.sciencedirect.com/science/article/pii/S0002944018302268
dc.rights© 2018 American Society for Investigative Pathology. Published by Elsevier Inc.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectInfant deathen
dc.subjectBioluminescent pathogensen
dc.subjectInfectious diseasesen
dc.subjectPreterm birthen
dc.subjectAscending vaginal infectionen
dc.titleAscending vaginal infection using bioluminescent bacteria evokes intrauterine inflammation, preterm birth, and neonatal brain injury in pregnant miceen
dc.typeArticle (peer-reviewed)en
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