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Updated: Jul 13, 2026

Imaging InlC Secretion to Investigate Cellular Infection by the Bacterial Pathogen Listeria monocytogenes
Published on: September 19, 2013
A PEST-like sequence in listeriolysin O essential for Listeria monocytogenes pathogenicity
1Department of Molecular and Cell Biology, Division of Infectious Diseases, School of Public Health, University of California, Berkeley, CA 94720, USA.
Abstract:
Establishment and maintenance of an intracellular niche are critical to the success of an intracellular pathogen. Here, the pore-forming protein listeriolysin O (LLO), secreted by Listeria monocytogenes, was shown to contain a PEST-like sequence (P, Pro; E, Glu; S, Ser; T, Thr) that is essential for the virulence and intracellular compartmentalization of this pathogen. Mutants lacking the PEST-like sequence entered the host cytosol but subsequently permeabilized and killed the host cell. LLO lacking the PEST-like sequence accumulated in the host-cell cytosol, suggesting that this sequence targets LLO for degradation. Transfer of the sequence to perfringolysin O transformed this toxic cytolysin into a nontoxic derivative that facilitated intracellular growth.
Insights
A PEST-like sequence in Listeria monocytogenes listeriolysin O (LLO) is crucial for pathogen virulence. This sequence targets LLO for degradation, preventing host cell damage and enabling intracellular survival.
Area of Science:
- Microbiology
- Cell Biology
- Pathogen-Host Interactions
Background:
- Intracellular pathogens require a protected niche for survival and replication within host cells.
- Listeria monocytogenes utilizes the pore-forming protein listeriolysin O (LLO) during its infection cycle.
Purpose of the Study:
- To investigate the role of a PEST-like sequence in LLO function, virulence, and intracellular compartmentalization.
- To determine the impact of this sequence on LLO's interaction with host cells.
Main Methods:
- Site-directed mutagenesis to create LLO mutants lacking the PEST-like sequence.
- Analysis of bacterial entry into host cells and subsequent intracellular fate.
- Assessment of host cell viability and integrity.
- Functional transfer of the PEST-like sequence to another cytolysin, perfringolysin O.
Main Results:
- LLO mutants lacking the PEST-like sequence entered the host cytosol but caused host cell permeabilization and death.
- LLO lacking the PEST-like sequence accumulated in the host cytosol, indicating it targets LLO for degradation.
- Transferring the PEST-like sequence to perfringolysin O rendered it non-toxic and promoted intracellular growth.
Conclusions:
- The PEST-like sequence in LLO is essential for Listeria monocytogenes virulence and proper intracellular compartmentalization.
- This sequence mediates LLO degradation, preventing premature host cell lysis and facilitating pathogen survival.
- The PEST-like sequence can be functionally transferred to other cytolysins to modulate their toxicity and promote intracellular growth.
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