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A Murine Model of Group B Streptococcus Vaginal Colonization
Published on: November 16, 2016
Human Milk Oligosaccharides Inhibit Group B Streptococcal Growth by Binding PcsB, an Essential Cell Wall Separation
Julie A Talbert1, Thomas L Kalmer1, Lee S Cantrell2
1Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37240, United States.
Human milk oligosaccharides (HMOs) inhibit Group B Streptococcus (GBS) by targeting the essential PcsB protein. This interaction disrupts bacterial cell division, offering a novel mechanism for antimicrobial action.
Area of Science:
- Microbiology
- Biochemistry
- Glycoscience
Background:
- Human milk oligosaccharides (HMOs) are known for their protective effects in the neonatal gut.
- Group B Streptococcus (GBS) is a significant cause of invasive perinatal infections.
Purpose of the Study:
- To elucidate the mechanism by which HMOs exert antimicrobial activity against GBS.
- To identify the specific molecular targets of HMOs in GBS.
Main Methods:
- Untargeted proteomics to identify bacterial protein changes.
- Protein domain purification and functional assays.
- In silico molecular docking and dynamics simulations.
- Microscale thermophoresis and turbidimetric assays.
Main Results:
- Proteomics revealed downregulation of PcsB, a key enzyme in bacterial cell division.
- Purified PcsB domain restored GBS growth in the presence of HMOs, confirming PcsB as an interaction partner.
- In silico and experimental assays identified specific fucosylated HMOs (LNFPI, LNFPIII) binding to PcsB.
- HMOs were shown to inhibit the enzymatic activity of PcsB's CHAP domain.
Conclusions:
- HMOs inhibit GBS growth by directly binding to the PcsB protein at its catalytic site.
- This binding event interferes with essential cell wall separation and division processes in GBS.
- The findings reveal a novel mechanism for HMO-mediated antimicrobial activity against GBS.
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