The Pore-Forming Toxin Listeriolysin O Mediates a Novel Entry Pathway of L. monocytogenes into Human Hepatocytes Original paper
Researched by:
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Divine Aleru
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Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Microbes
Microbes
Microbes are microscopic organisms living in and on the human body, shaping health through digestion, vitamin production, and immune protection. When microbial balance is disrupted, disease can occur. This guide explains key microbe types—bacteria, viruses, fungi, protozoa, and archaea—plus major pathogenic and beneficial examples.
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Divine Aleru
Read More
Researched by:
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Divine Aleru
ID
Divine Aleru
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was studied?
The study focused on the role of the pore-forming toxin, listeriolysin O (LLO), in the invasion of human hepatocytes by Listeria monocytogenes. Specifically, it investigates how LLO mediates a novel entry pathway, where the toxin perforates host cell membranes, triggering internalization of the bacterium and other particles such as polystyrene beads into the cells.
Who was studied?
The study focused on Listeria monocytogenes and its ability to invade human hepatocytes, specifically HepG2 cells. The research also examined the effects of listeriolysin O (LLO), the pore-forming toxin, in mediating the entry process. Additionally, the study included the use of Listeria innocua as a control to confirm that LLO could independently induce cell entry.
What were the most important findings?
The study found that LLO plays a crucial role in L. monocytogenes entry into human hepatocytes (HepG2 cells). LLO was shown to be sufficient to induce bacterial internalization into host cells, an activity previously attributed only to other virulence factors like InlA and InlB. It was demonstrated that LLO facilitates bacterial entry through a pore-dependent mechanism, where it forms large oligomeric complexes on the host cell membrane, enabling the bacterium to cross into the cytoplasm. This process is dynamin- and F-actin-dependent but clathrin-independent. The study also showed that LLO can induce the internalization of non-invasive Listeria innocua, which further confirmed that LLO is sufficient by itself to induce bacterial uptake into host cells. Additionally, the LLO-induced internalization pathway is distinct from conventional endocytosis pathways, as it involves the actin cytoskeleton and tyrosine kinase signaling.
What are the greatest implications of this study?
The greatest implication of this study is the identification of a new entry strategy used by Listeria monocytogenes for host cell invasion. This research reveals that LLO acts as a key virulence factor not only for bacterial survival within host cells but also for initiating the internalization process, potentially broadening our understanding of bacterial pathogenesis. Furthermore, the study suggests that similar pore-forming toxins from other pathogens might utilize a similar mechanism for host cell entry, opening new avenues for therapeutic interventions targeting this entry strategy. The study also underscores the importance of LLO in modulating the actin cytoskeleton and providing a mechanism for bacterial internalization independent of classical receptor-mediated endocytosis.
Listeria monocytogenes
Listeria monocytogenes is an opportunistic pathogen capable of surviving in diverse environments, including soil, water, and decaying vegetation. L. monocytogenes has the unique ability to evade the immune system by moving directly from cell to cell within the host. This intracellular lifestyle allows the bacterium to avoid extracellular immune detection, contributing to its ability to cause invasive diseases like meningitis and septicemia, particularly in the elderly and immunocompromised.