Bacterial Pili exploit integrin machinery to promote immune activation and efficient blood-brain barrier penetration.
Open accessAbstract
Group B Streptococcus (GBS) is the leading cause of meningitis in newborn infants. Bacterial cell surface appendages, known as pili, have been recently described in streptococcal pathogens, including GBS. The pilus tip adhesin, PilA, contributes to GBS adherence to blood-brain barrier (BBB) endothelium; however, the host receptor and the contribution of PilA in central nervous system (CNS) disease pathogenesis are unknown. Here we show that PilA binds collagen, which promotes GBS interaction with the α2β1 integrin resulting in activation of host chemokine expression and neutrophil recruitment during infection. Mice infected with the PilA-deficient mutant exhibit delayed mortality, a decrease in neutrophil infiltration and bacterial CNS dissemination. We find that PilA-mediated virulence is dependent on neutrophil influx as neutrophil depletion results in a decrease in BBB permeability and GBS–BBB penetration. Our results suggest that the bacterial pilus, specifically the PilA adhesin, has a dual role in immune activation and bacterial entry into the CNS. Group BStreptococcuscauses meningitis in newborn infants but how the bacterium crosses the blood-brain barrier is unknown. Here, the bacterial pili adhesion molecule, PilA, is shown to bind to collagen and promote binding of the bacteria to integrins expressed on the blood-brain endothelium.
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Bacterial presence in the meninges induces a strong inflammatory response, including production of multiple cytokines (TNF-alpha, IL-1-beta, and IL-6), and a massive infiltration of neutrophils, and these cytokines and neutrophils work to quell the infection but also drive the breakdown of endothelial cell tight junctions.
“Bacterial presence in the meninges induces a strong inflammatory response, including production of multiple cytokines (tumor necrosis factor (TNF)-alpha, interleukin (IL)-1-beta, and IL-6), and a massive infiltration of neutrophils”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Banerjee et al., 2011
GBS pilus protein PilA and Srr-1 interact with host ECM to promote BBB interactions and meningitis.
“Recently, we have demonstrated that the GBS pilus protein PilA and Srr-1 interact with components of the host extracellular matrix (ECM) to promote BBB interactions and the development of meningitis (8,9).”
From Bacterial induction of Snail1 contributes to blood-brain barrier disruption (2015) · cites this paper as [8]
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- Authors
- Banerjee, A., Kim, B. J., Carmona, E. M., Cutting, A. S., Gurney, M. A., Carlos, C., Feuer, R., Prasadarao, N. V., & Doran, K. S.
- Affiliations
- San Diego State University (US)
- University of Southern California (US)
- Corresponding author
- Doran, Kelly S.
- Venue
- Nature Communications
- Published
- 2011-09-06
- Volume
- 2
- Issue
- 1
- Pages
- 462-462
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC3195231
- OpenAlex
- W1997334188
- Cited by
- 142
- References
- 61
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 19 · 2023: 2 · 2022: 9 · 2021: 14 · 2020: 8 · 2019: 9 · 2018: 6 · 2017: 13 · 2016: 6 · 2015: 9 · 2014: 5 · 2013: 7 · 2012: 10
- FWCI
- 8.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (AI40567)
- University of California, San Diego
- National Institute of General Medical Sciences (T34GM008303)
- National Institute of Allergy and Infectious Diseases (R01AI040567, AI40567, R29AI040567)
- National Institute of Neurological Disorders and Stroke (R01NS051247, R01NS054108)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Neonatal and Maternal Infections
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Keywords
- Streptococcus agalactiae, bacterial pili, blood-brain barrier penetration, alpha2beta1 integrin, collagen binding, neutrophil recruitment, chemokine expression, meningitis, neonates, bacterial virulence, endothelial cell adhesion
- MeSH terms
- Animals, Bacterial Adhesion, Blood-Brain Barrier, Chemotaxis, Leukocyte, Neutrophils, Fimbriae, Bacterial, Streptococcus agalactiae, Signal Transduction, Interleukin-8, Meningitis, Bacterial, Chemokines, Integrin alpha2beta1, Mice, Focal Adhesion Protein-Tyrosine Kinases
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