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Role of fibronectin-binding MSCRAMMs in bacterial adherence and entry into mammalian cells
D Joh1, E R Wann, B Kreikemeyer
1Center for Extracellular Matrix Biology, Albert B. Alkek Institute of Biosciences and Technology, Texas A&M University System, Houston 77030, USA.
Abstract:
Most bacterial infections are initiated by the adherence of microorganisms to host tissues. This process involves the interaction of specific bacterial surface structures, called adhesins, with host components. In this review, we discuss a group of microbial adhesins known as Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs) which recognize and bind FN. The interaction of bacteria with FN is believed to contribute significantly to the virulence of a number of microorganisms, including staphylococci and streptococci. Several FN-binding MSCRAMMs of staphylococci and streptococci exhibit a similar structural organization and mechanism of ligand recognition. The ligand-binding domain consists of tandem repeats of a approximately 45 amino acid long unit which bind to the 29-kDa N-terminal region of FN. The binding mechanism is unusual in that the repeat units are unstructured and appear to undergo a conformational change upon ligand binding. Apart from supporting bacterial adherence, FN is also involved in bacterial entry into non-phagocytic mammalian cells. A sandwich model has been proposed in which FN forms a molecular bridge between MSCRAMMs on the bacterial surface and integrins on the host cell. However, the precise mechanism of bacterial invasion and the roles of FN and integrins in this process have yet to be fully elucidated.
Insights
Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs) bind fibronectin (FN), aiding bacterial adherence and invasion. This interaction involves unique structural repeats and a proposed "sandwich model" with host cell integrins.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Bacterial infections often begin with microbial adherence to host tissues.
- Adhesins, specific bacterial surface structures, mediate this interaction with host components.
- Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs) are key adhesins that bind fibronectin (FN).
Purpose of the Study:
- To review the role of FN-binding MSCRAMMs in bacterial adherence and invasion.
- To discuss the structure and ligand-binding mechanism of these MSCRAMMs.
- To explore the proposed "sandwich model" of bacterial entry involving FN and host cell integrins.
Main Methods:
- Review of existing literature on MSCRAMMs, fibronectin binding, and bacterial invasion.
- Analysis of structural data for FN-binding MSCRAMMs.
- Discussion of proposed models for bacterial-host cell interactions.
Main Results:
- FN-binding MSCRAMMs from staphylococci and streptococci share structural similarities.
- Their ligand-binding domain features tandem repeats that bind the N-terminal region of FN.
- These repeat units are unstructured and undergo conformational changes upon FN binding.
Conclusions:
- FN-MSCRAMM interaction is crucial for bacterial virulence and adherence.
- FN mediates bacterial entry into non-phagocytic cells via a proposed "sandwich model" with integrins.
- Further research is needed to fully elucidate the mechanisms of bacterial invasion involving FN and integrins.