Internalin
A family of proteins associated with bacterial pathogenesis
Internalin refers to a family of proteins that are primarily associated with the pathogenesis of certain bacteria, notably Listeria monocytogenes. These proteins play a crucial role in the bacteria's ability to invade host cells, facilitating infection and spread within the host organism.
Structure and Function
Internalins are characterized by the presence of leucine-rich repeats (LRRs), which are structural motifs that mediate protein-protein interactions. The LRRs in internalins are crucial for their ability to bind to host cell receptors, thereby promoting bacterial entry into the host cells.
The most well-studied internalin is Internalin A (InlA), which binds to the host cell receptor E-cadherin. This interaction is essential for the invasion of epithelial cells by Listeria monocytogenes. Another important member of this family is Internalin B (InlB), which interacts with the host receptor Met, a receptor tyrosine kinase, facilitating bacterial entry into a variety of cell types.
Role in Pathogenesis
Internalins are virulence factors that enable Listeria monocytogenes to breach the intestinal barrier, cross the blood-brain barrier, and infect the placenta. This ability to invade different tissues makes Listeria infections particularly dangerous, especially in immunocompromised individuals, pregnant women, and the elderly.
The interaction between internalins and their respective host receptors triggers a series of cellular events that lead to the internalization of the bacteria. This process involves cytoskeletal rearrangements and the formation of a phagocytic cup that engulfs the bacterium, allowing it to enter the host cell.
Genetic Regulation
The expression of internalins is tightly regulated by the bacterial cell in response to environmental cues. The prfA gene is a key regulator of virulence gene expression in Listeria monocytogenes, including the genes encoding internalins. The PrfA protein acts as a transcriptional activator, ensuring that internalins are expressed when the bacteria are in a host environment.
Clinical Implications
Understanding the function of internalins is critical for developing strategies to prevent and treat infections caused by Listeria monocytogenes. Targeting the interaction between internalins and their host receptors could provide a therapeutic approach to block bacterial invasion and reduce the severity of infection.
Research Directions
Ongoing research is focused on elucidating the detailed mechanisms of internalin-mediated invasion, the structural biology of internalin-receptor interactions, and the development of inhibitors that can block these interactions. Additionally, studies are exploring the role of internalins in the immune response and their potential as vaccine targets.
Also see
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Contributors: Prab R. Tumpati, MD