Related Experiment Video
Updated: Aug 9, 2026
Invasion of Human Cells by a Bacterial Pathogen
Published on: March 21, 2011
Genetic dissection of the Streptococcus pyogenes M1 protein: regions involved in fibronectin binding and
D Cue1, H Lam, P P Cleary
1Department of Microbiology, University of Minnesota, Minneapolis, MN, U.S.A.
Abstract:
Entry of serotype M1 Streptococcus pyogenes into host cells depends on binding of the host glycoprotein fibronectin (Fn) by the bacterial M1 protein. The present study was undertaken to localize the Fn binding region in M1 and assess other potential functions of M1. A set of recombinant M1 protein fragments were assayed for their capacities to bind Fn and inhibit ingestion of streptococci by epithelial cells. M1 protein, M6 protein and internally-deleted derivatives of M1 were expressed on the surface of Lactococcus lactis. Lactococci that expressed M1 or M6 protein bound Fn and were efficiently taken up by epithelial cells. Deletion of both the N-terminal A and B repeats regions of M1 abrogated Fn binding and intracellular invasion. Deletion of either the A domain (M1DeltaA) or B repeats (M1DeltaB) significantly reduced, but did not completely eliminate, Fn binding indicating that M1 protein may possess two independent Fn binding sites. Fn binding by the M1DeltaA or M1DeltaB proteins was insufficient for efficient invasion, however, suggesting that M protein binding alters the structure of Fn that, in turn, affects the interaction between Fn and epithelial cells. Although expression of M1, M6 or M1DeltaB proteins led to aggregation of lactococcal cells, aggregation did not significantly contribute to invasion efficiency.
Insights
The M1 protein of Streptococcus pyogenes binds fibronectin (Fn) using its N-terminal regions, which is crucial for bacterial entry into host cells. This binding interaction is key for invasion, not cell aggregation.
Area of Science:
- Microbiology
- Molecular Biology
- Cell Biology
Background:
- Streptococcus pyogenes serotype M1 invades host cells.
- This invasion is mediated by the M1 protein binding to host fibronectin (Fn).
Purpose of the Study:
- To identify the fibronectin binding region within the M1 protein.
- To investigate other functions of the M1 protein related to host cell invasion.
Main Methods:
- Recombinant M1 protein fragments were created and tested for Fn binding.
- M1 and its derivatives were expressed on Lactococcus lactis to assess Fn binding and epithelial cell uptake.
- Specific domains (A, B repeats) of M1 were deleted to analyze their role in Fn binding and invasion.
Main Results:
- Deletion of both N-terminal A and B repeat regions of M1 abolished Fn binding and invasion.
- Partial deletions (M1DeltaA, M1DeltaB) reduced Fn binding, suggesting two binding sites.
- Reduced Fn binding by M1 variants was insufficient for efficient host cell invasion.
- Bacterial cell aggregation did not significantly contribute to invasion efficiency.
Conclusions:
- The N-terminal A and B repeat regions of the M1 protein are essential for fibronectin binding and host cell invasion.
- M1 protein binding to Fn likely alters Fn structure, facilitating epithelial cell interaction and invasion.
- M1 protein possesses at least two distinct fibronectin binding sites.
Related Concept Videos
01:20Determinants of Bacterial Pathogenicity and Virulence
01:27Streptococcal Pharyngitis