The Group B Streptococcal Adhesin BspC Interacts with Host Cytokeratin 19 To Promote Colonization of the Female Reproductive Tract

Haider S Manzer, Dustin T Nguyen, Joo Youn Park, Nogi Park, Keun Seok Seo, Justin A Thornton, Angela H Nobbs, Kelly S Doran*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

2 Citations (Scopus)
45 Downloads (Pure)


Streptococcus agalactiae, otherwise known as Group B Streptococcus (GBS), is an opportunistic pathogen that vaginally colonizes approximately one third of healthy women. During pregnancy, this can lead to in utero infection, resulting in premature rupture of membranes, chorioamnionitis, and stillbirths. Furthermore, GBS causes serious infection in newborns, including sepsis, pneumonia, and meningitis. Previous studies have indicated that GBS antigen (Ag) I/II family proteins promote interaction with vaginal epithelial cells; thus, we hypothesized that the Ag I/II Group B streptococcal surface protein C (BspC) contributes to GBS colonization of the female reproductive tract (FRT). Here, we show that a ΔbspC mutant has decreased bacterial adherence to vaginal, ecto-, and endocervical cells, as well as decreased auto-aggregation and biofilm-like formation on cell monolayers. Using a murine model of vaginal colonization, we observed that the ΔbspC mutant strain exhibited a significant fitness defect compared to wild-type (WT) GBS and was less able to ascend to the cervix and uterus in vivo, resulting in reduced neutrophil chemokine signaling. Furthermore, we determined that BspC interacts directly with the host intermediate filament protein cytokeratin 19 (K19). Surface localization of K19 was increased during GBS infection, and interaction was mediated by the BspC variable (V) domain. Finally, mice treated with a drug that targets the BspC V-domain exhibited reduced bacterial loads in the vaginal lumen and reproductive tissues. These results demonstrate the importance of BspC in promoting GBS colonization of the FRT and that it may be targeted therapeutically to reduce GBS vaginal persistence and ascending infection. IMPORTANCE Group B Streptococcus (GBS) asymptomatically colonizes the female reproductive tract (FRT) of up to one third of women, but GBS carriage can lead to adverse pregnancy outcomes, including premature rupture of membranes, preterm labor, and chorioamnionitis. GBS colonization during pregnancy is also the largest predisposing factor for neonatal GBS disease, including pneumonia, sepsis, and meningitis. The molecular interactions between bacterial surface proteins and the host cell receptors that promote GBS colonization are vastly understudied, and a better understanding would facilitate development of novel therapeutics to prevent GBS colonization and disease. Here, we characterize the role of the GBS surface protein BspC in colonization of the FRT. We show for the first time that GBS infection induces cytokeratin 19 (K19) surface localization on vaginal epithelial cells; GBS then uses the BspC V-domain to interact with K19 to promote colonization and ascending infection. Furthermore, this interaction can be targeted therapeutically to reduce GBS carriage.

Original languageEnglish
Article numbere0178122
Issue number5
Early online date7 Sept 2022
Publication statusPublished - 26 Oct 2022

Bibliographical note

Funding Information:
We acknowledge the Biophysics Core and Barbara Davis Center Sequencing Core at the University of Colorado Anschutz Medical Campus. We thank Tibor Pechan of the MSU Institute for Genomics, Biocomputing & Biotechnology (IGBB) for his assistance with mass spectrometry analysis. We also thank Liwen Deng for her early contribution and technical assistance. This work was supported by grants NIH/NIAID R01 AI153332 and NIH/NINDS R01NS116716 to K.S.D. as well as the T32 5T32AI052066-18 and F31 AI164674-01 to H.S.M.

Publisher Copyright:
© 2022 Manzer et al.


Dive into the research topics of 'The Group B Streptococcal Adhesin BspC Interacts with Host Cytokeratin 19 To Promote Colonization of the Female Reproductive Tract'. Together they form a unique fingerprint.

Cite this