Group B Streptococcus CAMP Factor Does Not Contribute to Interactions with the Vaginal Epithelium and Is Dispensable for Vaginal Colonization in Mice
ABSTRACT The Gram-positive pathogen group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections, preterm birth, and stillbirth. Although maternal GBS vaginal colonization is a risk factor for GBS-associated adverse birth outcomes, mechanisms promoting GBS vaginal persistence are...
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Language: | English |
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American Society for Microbiology
2021-12-01
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Series: | Microbiology Spectrum |
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Online Access: | https://journals.asm.org/doi/10.1128/Spectrum.01058-21 |
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author | Mallory B. Ballard Vicki Mercado-Evans Madelynn G. Marunde Hephzibah Nwanosike Jacob Zulk Kathryn A. Patras |
author_facet | Mallory B. Ballard Vicki Mercado-Evans Madelynn G. Marunde Hephzibah Nwanosike Jacob Zulk Kathryn A. Patras |
author_sort | Mallory B. Ballard |
collection | DOAJ |
description | ABSTRACT The Gram-positive pathogen group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections, preterm birth, and stillbirth. Although maternal GBS vaginal colonization is a risk factor for GBS-associated adverse birth outcomes, mechanisms promoting GBS vaginal persistence are not fully defined. GBS possesses a broadly conserved small molecule, CAMP factor, that is co-hemolytic in the presence of Staphylococcus aureus sphingomyelinase C. While this co-hemolytic reaction is commonly used by clinical laboratories to identify GBS, the contribution of CAMP factor to GBS vaginal persistence is unknown. Using in vitro biofilm, adherence and invasion assays with immortalized human vaginal epithelial VK2 cells, and a mouse model of GBS vaginal colonization, we tested the contribution of CAMP factor using GBS strain COH1 and its isogenic CAMP-deficient mutant (Δcfb). We found no evidence for CAMP factor involvement in GBS biofilm formation, or adherence, invasion, or cytotoxicity toward VK2 cells in the presence or absence of S. aureus. Additionally, there was no difference in vaginal burdens or persistence between COH1 and Δcfb strains in a murine colonization model. In summary, our results using in vitro human cell lines and murine models do not support a critical role for CAMP factor in promoting GBS vaginal colonization. IMPORTANCE Group B Streptococcus (GBS) remains a pervasive pathogen for pregnant women and their newborns. Maternal screening and intrapartum antibiotic prophylaxis to GBS-positive mothers have reduced, but not eliminated GBS neonatal disease, and have not impacted GBS-associated preterm birth or stillbirth. Additionally, this antibiotic exposure is associated with adverse effects on the maternal and neonatal microbiota. Identifying key GBS factors important for maternal vaginal colonization will foster development of more targeted, alternative therapies to antibiotic treatment. Here, we investigate the contribution of a broadly conserved GBS determinant, CAMP factor, to GBS vaginal colonization and find that CAMP factor is unlikely to be a biological target to control maternal GBS colonization. |
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format | Article |
id | doaj.art-56994e8e72b74dd6ba1a612a7b910a88 |
institution | Directory Open Access Journal |
issn | 2165-0497 |
language | English |
last_indexed | 2024-12-18T02:46:11Z |
publishDate | 2021-12-01 |
publisher | American Society for Microbiology |
record_format | Article |
series | Microbiology Spectrum |
spelling | doaj.art-56994e8e72b74dd6ba1a612a7b910a882022-12-21T21:23:33ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972021-12-019310.1128/Spectrum.01058-21Group B Streptococcus CAMP Factor Does Not Contribute to Interactions with the Vaginal Epithelium and Is Dispensable for Vaginal Colonization in MiceMallory B. Ballard0Vicki Mercado-Evans1Madelynn G. Marunde2Hephzibah Nwanosike3Jacob Zulk4Kathryn A. Patras5Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USADepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USADepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USADepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USADepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USADepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USAABSTRACT The Gram-positive pathogen group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections, preterm birth, and stillbirth. Although maternal GBS vaginal colonization is a risk factor for GBS-associated adverse birth outcomes, mechanisms promoting GBS vaginal persistence are not fully defined. GBS possesses a broadly conserved small molecule, CAMP factor, that is co-hemolytic in the presence of Staphylococcus aureus sphingomyelinase C. While this co-hemolytic reaction is commonly used by clinical laboratories to identify GBS, the contribution of CAMP factor to GBS vaginal persistence is unknown. Using in vitro biofilm, adherence and invasion assays with immortalized human vaginal epithelial VK2 cells, and a mouse model of GBS vaginal colonization, we tested the contribution of CAMP factor using GBS strain COH1 and its isogenic CAMP-deficient mutant (Δcfb). We found no evidence for CAMP factor involvement in GBS biofilm formation, or adherence, invasion, or cytotoxicity toward VK2 cells in the presence or absence of S. aureus. Additionally, there was no difference in vaginal burdens or persistence between COH1 and Δcfb strains in a murine colonization model. In summary, our results using in vitro human cell lines and murine models do not support a critical role for CAMP factor in promoting GBS vaginal colonization. IMPORTANCE Group B Streptococcus (GBS) remains a pervasive pathogen for pregnant women and their newborns. Maternal screening and intrapartum antibiotic prophylaxis to GBS-positive mothers have reduced, but not eliminated GBS neonatal disease, and have not impacted GBS-associated preterm birth or stillbirth. Additionally, this antibiotic exposure is associated with adverse effects on the maternal and neonatal microbiota. Identifying key GBS factors important for maternal vaginal colonization will foster development of more targeted, alternative therapies to antibiotic treatment. Here, we investigate the contribution of a broadly conserved GBS determinant, CAMP factor, to GBS vaginal colonization and find that CAMP factor is unlikely to be a biological target to control maternal GBS colonization.https://journals.asm.org/doi/10.1128/Spectrum.01058-21group B StreptococcusStaphylococcus aureusCAMP factorvaginal colonizationbiofilm |
spellingShingle | Mallory B. Ballard Vicki Mercado-Evans Madelynn G. Marunde Hephzibah Nwanosike Jacob Zulk Kathryn A. Patras Group B Streptococcus CAMP Factor Does Not Contribute to Interactions with the Vaginal Epithelium and Is Dispensable for Vaginal Colonization in Mice Microbiology Spectrum group B Streptococcus Staphylococcus aureus CAMP factor vaginal colonization biofilm |
title | Group B Streptococcus CAMP Factor Does Not Contribute to Interactions with the Vaginal Epithelium and Is Dispensable for Vaginal Colonization in Mice |
title_full | Group B Streptococcus CAMP Factor Does Not Contribute to Interactions with the Vaginal Epithelium and Is Dispensable for Vaginal Colonization in Mice |
title_fullStr | Group B Streptococcus CAMP Factor Does Not Contribute to Interactions with the Vaginal Epithelium and Is Dispensable for Vaginal Colonization in Mice |
title_full_unstemmed | Group B Streptococcus CAMP Factor Does Not Contribute to Interactions with the Vaginal Epithelium and Is Dispensable for Vaginal Colonization in Mice |
title_short | Group B Streptococcus CAMP Factor Does Not Contribute to Interactions with the Vaginal Epithelium and Is Dispensable for Vaginal Colonization in Mice |
title_sort | group b streptococcus camp factor does not contribute to interactions with the vaginal epithelium and is dispensable for vaginal colonization in mice |
topic | group B Streptococcus Staphylococcus aureus CAMP factor vaginal colonization biofilm |
url | https://journals.asm.org/doi/10.1128/Spectrum.01058-21 |
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