Internalin BEdit
Internalin B is a prominent virulence factor of the foodborne pathogen Listeria monocytogenes. As a member of the internalin protein family, Internalin B (InlB) promotes entry into non-phagocytic host cells by engaging the host receptor Met. The InlB protein is encoded by the inlB gene and is secreted and anchored to the bacterial surface, where its leucine-rich repeats mediate receptor binding. This interaction triggers signaling pathways that reorganize the host cell cytoskeleton and drive internalization of the bacterium, contributing to the ability of Listeria to traverse intestinal barriers and disseminate to susceptible tissues such as the liver, placenta, and central nervous system.
InlB functions in concert with other factors, most notably InlA, to facilitate invasion of a variety of cell types. The study of InlB and related proteins has offered important insights into receptor tyrosine kinase signaling, endocytosis, and bacterial pathogenesis. The discovery of Internalin B and its relatives helped establish a framework for understanding how surface proteins on Gram-positive pathogens engage host cell adhesion and signaling machinery. For broader context, see Listeria monocytogenes, Internalin family, and InlA.
Biology and mechanism
Structure and localization
Internalin B is anchored to the surface of Listeria monocytogenes via a cell wall–anchoring mechanism that involves an LPXTG motif recognized by the bacterial enzyme Sortase A. The protein is produced with an N-terminal signal peptide for export through the Sec pathway and features a high-density region of leucine-rich repeats that form a curved, ligand-binding surface. The combination of these features positions InlB to interact efficiently with host cell receptors on the exterior of target cells. See LPXTG motif and Leucine-rich repeat for related structural concepts.
Receptors and binding
The principal host receptor for InlB is the Met receptor, a receptor tyrosine kinase that responds to hepatocyte growth factor in normal physiology. Binding of InlB to Met stimulates receptor dimerization and autophosphorylation, initiating downstream signaling. This signaling cascade recruits and activates a network of effectors that control the actin cytoskeleton and vesicular trafficking. For background on Met signaling, see Met and PI3K; for cytoskeletal aspects, see Actin cytoskeleton and Rac1.
In addition to Met, some internalins can interact with alternative cellular targets in certain contexts, providing redundancy or tissue-specific entry pathways. InlA, for example, engages E-cadherin to promote invasion; the two internalins often act cooperatively during infection, see InlA.
Signaling and entry
Met engagement by InlB activates signaling through pathways such as PI3K/Akt and small GTPases like Rac1, leading to cytoskeletal rearrangements and membrane ruffling that envelop the bacterium. This enables a form of endocytosis that allows Listeria to penetrate non-professional phagocytes, escape from phagosomes, and replicate intracellularly. The broader topic of endocytosis and cytoskeletal remodeling is covered under Endocytosis and Actin cytoskeleton.
Host range and cell types
InlB contributes to Listeria’s ability to invade a range of cell types, including hepatocytes and epithelial cells lining the intestinal tract. Its activity complements InlA-mediated entry, broadening the pathogen’s tropism and helping explain how Listeria crosses barriers such as the intestinal epithelium and, in animal models, placental and blood-brain barriers. See Listeria monocytogenes, InlA, and placental infection for related themes.
Role in disease and pathogenicity
Pathogenesis and tissue tropism
InlB is a key determinant of intracellular invasion and dissemination. By activating Met signaling, InlB helps Listeria induce uptake into host cells and subsequently replicate within the cytoplasm. The combined action of InlB with other virulence factors shapes tissue tropism and disease potential, explaining why certain Listeria infections can invade the placenta or central nervous system under appropriate circumstances. For context on Listeria pathogenesis, see Listeria monocytogenes#Pathogenesis.
Regulation and strain variation
Expression of inlB is regulated in concert with other virulence genes by global regulators that sense environmental conditions encountered within the host, such as the transcriptional activator prfA and related regulators. Different strains of L. monocytogenes can vary in the level of InlB produced, influencing virulence and host cell entry efficiency. See prfA and Virulence factors for related regulatory concepts.
Interplay with other virulence factors
Internalin B does not act alone. Its contribution to invasion is often synergistic with InlA and other surface proteins, enhancing the efficiency of host cell entry and subsequent intracellular survival. The cooperative action of multiple internalins illustrates a broader principle of bacterial pathogenesis: redundancy and synergy among adhesins and invasins increase the reliability of host invasion. See InlA and Internalin family for broader context.
Regulation, research, and applications
Research use and molecular tools
Because InlB can trigger Met signaling and endocytosis, researchers have used InlB and related internalins as tools to study receptor tyrosine kinase signaling and endocytic pathways. Engineered variants and fusion constructs have been explored for cellular delivery and targeting applications, illustrating how bacterial virulence factors can inform cell biology and biotechnology. See Met and drug delivery for related topics, as well as cell biology techniques.
Vaccine and therapeutic considerations
Understanding InlB’s role in invasion informs both vaccine design and strategies to mitigate infection. Attenuated strains lacking key virulence determinants, or subunit vaccines targeting the InlB–Met interaction, are topics of ongoing research in the broader effort to prevent listeriosis and related diseases. See Listeria monocytogenes#Vaccines for related discussions.
Controversies and policy considerations
Dual-use research and oversight
Research on virulence factors such as InlB sits at a crossroads of scientific opportunity and dual-use risk. While probing the mechanisms of host invasion can yield benefits for vaccines, therapeutics, and basic biology, there is concern about enabling misuse through increased understanding or access to reagents. A risk-based, proportionate approach to oversight—one that safeguards public safety without unnecessarily hindering legitimate inquiry—is widely advocated in policy discussions. See biosecurity and gain-of-function research for related policy discussions.
Regulation and scientific progress
Some observers argue that excessive or ideologically driven constraints on research can slow innovation and competitiveness in biotechnology. From a practical perspective, policymakers are urged to emphasize evidence-based risk assessment, incremental oversight, and germane accountability rather than broad, reflexive restrictions. Proponents of balanced governance maintain that safe, well-governed research remains essential to public health and economic vitality. See science policy and biotechnology regulation for broader debates.
Critics and counterpoints
Critiques of overbroad political criticism of science contend that it can obscure legitimate safety concerns and hinder progress by conflating regulatory prudence with political ideology. The aim, in this view, is to maintain rigorous safety standards while preserving the ability of researchers to pursue meaningful, impactful work. See discussions under science communication and risk assessment for related perspectives.