Streptococcus agalactiae npx Is Required for Survival in Human Placental Macrophages and Full Virulence in a Model of Ascending Vaginal Infection during Pregnancy

dc.contributor.authorLu, Jacky
dc.contributor.authorMoore, Rebecca E.
dc.contributor.authorSpice, Sabrina K.
dc.contributor.authorDoster, Ryan S.
dc.contributor.authorGuevara, Miriam A.
dc.contributor.authorFrancis, Jamisha D.
dc.contributor.authorNoble, Kristen N.
dc.contributor.authorRogers, Lisa M.
dc.contributor.authorTalbert, Julie A.
dc.contributor.authorKorir, Michelle L.
dc.contributor.authorTownsend, Steven D.
dc.contributor.authorAronoff, David M.
dc.contributor.authorManning, Shannon D.
dc.contributor.authorGaddy, Jennifer A.
dc.contributor.departmentMedicine, School of Medicine
dc.date.accessioned2024-04-25T15:42:34Z
dc.date.available2024-04-25T15:42:34Z
dc.date.issued2022-11-21
dc.description.abstractStreptococcus agalactiae, also known as group B Streptococcus (GBS), is a Gram-positive encapsulated bacterium that colonizes the gastrointestinal tract of 30 to 50% of humans. GBS causes invasive infection during pregnancy that can lead to chorioamnionitis, funisitis, preterm prelabor rupture of membranes (PPROM), preterm birth, neonatal sepsis, and maternal and fetal demise. Upon infecting the host, GBS encounters sentinel innate immune cells, such as macrophages, within reproductive tissues. Once phagocytosed by macrophages, GBS upregulates the expression of the gene npx, which encodes an NADH peroxidase. GBS mutants with an npx deletion (Δnpx) are exquisitely sensitive to reactive oxygen stress. Furthermore, we have shown that npx is required for GBS survival in both THP-1 and placental macrophages. In an in vivo murine model of ascending GBS vaginal infection during pregnancy, npx is required for invading reproductive tissues and is critical for inducing disease progression, including PPROM and preterm birth. Reproductive tissue cytokine production was also significantly diminished in Δnpx mutant-infected animals compared to that in animals infected with wild-type (WT) GBS. Complementation in trans reversed this phenotype, indicating that npx is critical for GBS survival and the initiation of proinflammatory signaling in the gravid host.
dc.eprint.versionFinal published version
dc.identifier.citationLu, J., Moore, R. E., Spicer, S. K., Doster, R. S., Guevara, M. A., Francis, J. D., Noble, K. N., Rogers, L. M., Talbert, J. A., Korir, M. L., Townsend, S. D., Aronoff, D. M., Manning, S. D., & Gaddy, J. A. (2022). Streptococcus agalactiae npx Is Required for Survival in Human Placental Macrophages and Full Virulence in a Model of Ascending Vaginal Infection during Pregnancy. mBio, 13(6), e02870-22. https://doi.org/10.1128/mbio.02870-22
dc.identifier.urihttps://hdl.handle.net/1805/40242
dc.language.isoen_US
dc.publisherAmerican Society for Microbiology
dc.relation.isversionof10.1128/mbio.02870-22
dc.relation.journalmBio
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePublisher
dc.subjectROS
dc.subjectStreptococcus
dc.subjectinfection
dc.subjectinnate immunity
dc.subjectreactive oxygen species
dc.titleStreptococcus agalactiae npx Is Required for Survival in Human Placental Macrophages and Full Virulence in a Model of Ascending Vaginal Infection during Pregnancy
dc.typeArticle
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