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Updated: Jul 10, 2026
A Murine Model of Group B Streptococcus Vaginal Colonization
Published on: November 16, 2016
Effects of complement regulators bound to Escherichia coli K1 and Group B Streptococcus on the interaction with host
Ravi Maruvada1, Anna M Blom, Nemani V Prasadarao
1Division of Infectious Diseases, The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
Insights
Neonatal meningitis bacteria Escherichia coli K1 and Group B Streptococcus (GBS) interact differently with complement proteins. Adult serum complement prevents E. coli invasion but enhances GBS invasion, impacting host defenses.
Area of Science:
- Immunology
- Microbiology
- Neonatal Research
Background:
- Escherichia coli K1 and Group B Streptococcus (GBS) are leading causes of neonatal meningitis.
- The complement system is a crucial host defense mechanism that opsonizes bacteria for phagocytosis.
- Bacteria like E. coli and GBS employ complement regulators to evade immune responses.
Purpose of the Study:
- To investigate the deposition and effects of complement proteins from neonatal and adult serum on E. coli and GBS.
- To understand how complement-mediated interactions influence bacterial invasion and phagocytosis by host cells.
- To elucidate the specific roles of complement regulators in these interactions.
Main Methods:
- Treatment of E. coli and GBS with adult and neonatal human serum.
- Assessment of bacterial invasion into human brain microvascular endothelial cells.
- Evaluation of bacterial phagocytosis and survival using THP-1 cells and differentiated macrophages.
- Identification of bound complement inhibitors.
Main Results:
- Adult serum complement inhibited E. coli invasion but enhanced GBS invasion into endothelial cells.
- Complement-coated E. coli were not phagocytosed, while GBS were efficiently phagocytosed and survived.
- Neonatal (cord) serum had no significant effect on the invasion or phagocytosis of either bacterium.
- C4b-binding protein mediated the inhibitory effect on E. coli, and Factor H mediated the effect on GBS.
Conclusions:
- E. coli and GBS exhibit distinct strategies for evading or utilizing complement-mediated host defenses during neonatal meningitis.
- Complement deposition from adult serum differentially affects bacterial interaction with host cells, highlighting age-dependent immune responses.
- Understanding these contrasting mechanisms is vital for developing targeted therapies against neonatal bacterial meningitis.
Abstract:
Escherichia coli K1 and Group B Streptococcus (GBS) are the most common bacteria that cause meningitis during the neonatal period. Complement, the first line of defence in the host, acts on these bacteria to opsonize with various components of complement for subsequent presentation to phagocytes. To counteract these opsonization effects, E. coli and GBS bind to the complement regulators C4 binding protein and Factor H, respectively. Nonetheless, the deposition of complement components on these two bacteria from neonatal serum and their effect on the host cell interaction is unclear. Here we demonstrated that the deposition of complement proteins from adult serum prevented the invasion of E. coli into human brain microvascular endothelial cells, whereas the invasion of GBS was enhanced. In contrast, treatment with cord serum had no effect on the invasion of both these bacteria. We also examined the effect of the deposited complement proteins on phagocytosis using THP-1 cells and THP-1 cells differentiated into macrophages. Escherichia coli treated with adult serum neither attached nor entered these cells, whereas GBS was phagocytosed and survived efficiently. We further demonstrate that the inhibitory effect of complement proteins is the result of the bound complement inhibitors C4b-binding protein, in the case of E. coli, and Factor H, in the case of GBS. Taken together, these results suggest that E. coli and GBS utilize contrasting mechanisms of complement-mediated interactions with their target cells for successful establishment of disease.
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