Chlamydia pneumoniae, a notorious pathogen, has developed remarkable strategies to manipulate human cells to its advantage. Researchers have unveiled the intricate mechanisms the bacteria employ, including the use of “molecular mimicry” to hijack the host’s endocytic machinery. This captivating discovery sheds light on how these microbes can contribute to conditions like Alzheimer’s disease, Reiter’s disease, and arteriosclerosis. Understanding these strategies could pave the way for novel therapeutic approaches.
Chlamydia’s Ingenious Exploitation of Host Cells
Bacteria, the notorious pathogens, have developed various strategies to leverage human cells as hosts for their own advantage. Researchers at Heinrich Heine University Düsseldorf (HHU) have uncovered the intricate attack methods employed by the bacterium Chlamydia pneumoniae (C. pneumoniae).
The team, led by Senior Professor Dr. Johannes H. Hegemann, examined the infection mechanisms of this pathogen. Their findings, published in Nature Communications, reveal how C. pneumoniae uses “molecular mimicry” to infiltrate and manipulate the host cell. This bacterium can only reproduce inside a host cell, and it has mastered the art of hijacking the cell’s endocytic machinery to achieve this goal.
The Chlamydia Infiltration: Exploiting the Host’s Endocytic Machinery
When C. pneumoniae binds to the outside of a human cell, it injects a chlamydial protein called ‘SemD’ into its future host. This protein then binds to the membrane of the vesicle that forms during the endocytic process, activating the actin cytoskeleton. This allows the plasma membrane to fully engulf the large Chlamydium, a feat that is not normally intended for the transport of such large structures.
Interestingly, the SemD protein is optimally tailored to the human protein N-WASP, the key activator of the endocytic process. In fact, the binding site of SemD looks exactly like the human protein Cdc42, which normally activates N-WASP. SemD even displaces Cdc42 from N-WASP, allowing it to bind more effectively and hijack the endocytic machinery for the bacterium’s own benefit.
Unraveling the Structural Secrets of Chlamydia’s Molecular Mimicry
To understand the structural and functional mechanisms behind this ingenious infiltration strategy, the researchers cultivated tiny crystals of the SemD protein with N-WASP and examined their structure. This was a collaborative effort between the research group at the Institute for Functional Microbial Genomics, the Center for Structural Studies (CSS), the Center for Advanced Imaging (CAi), and the Institute of Biochemistry and Molecular Biology II at the Medical Faculty.
The researchers hope that this newfound knowledge will pave the way for the development of agents that can prevent the specific interaction between the bacterial and human proteins, effectively blocking C. pneumoniae infections. This groundbreaking discovery not only sheds light on the sophisticated tactics employed by Chlamydia but also opens up new avenues for potential therapeutic interventions.
