Listeriolysin O
You don't need to be Editor-In-Chief to add or edit content to WikiDoc. You can begin to add to or edit text on this WikiDoc page by clicking on the edit button at the top of this page. Next enter or edit the information that you would like to appear here. Once you are done editing, scroll down and click the Save page button at the bottom of the page.
Listeriolysin O (LLO) is a hemolysin produced by the bacterium Listeria monocytogenes, the pathogen responsible for causing listeriosis. The toxin may be considered a virulence factor, since it is crucial for the virulence of L. monocytogenes.[1]
Contents |
Biochemistry
Listeriolysin O is a thiol-activated cholesterol-dependent pore forming toxin protein; hence, it is activated by reducing agents and inhibited by oxidizing agents.[1] However, LLO differs from other thiol-activated toxins, since its cytolytic activity is maximized at a pH of 5.5.[1].
By maximizing activity at a pH of 5.5, LLO is selectively activated within the acidic phagosomes (average pH ~ 5.9) of cells that have phagocytosed L. monocytogenes.[1] After LLO lyses the phagosome, the bacterium escapes into the cytosol, where it can grow intracellularly. Upon release from the phagosome, the toxin has reduced activity in the more basic cytosol.
Hence, LLO permits L. monocytogenes to escape from phagosomes into the cytosol without damaging the plasma membrane of the infected cell. This allows the bacteria to live intracellularly, where they are protected from extracellular immune system factors such as the complement system and antibodies.
LLO also causes dephosphorylation of histone H3 and deacetylation of histone H4 during the early phases of infection, prior to entry of L. monocytogenes into the host cell.[1] The pore-forming activity is not involved in causing the histone modifications. The alterations of the histones cause the down regulation of genes encoding proteins involved in the inflammatory response. Thus, LLO may be important in subverting the host immune response to L. monocytogenes.[1]
A PEST-like sequence is present in LLO and is considered essential for virulence, since mutants lacking the sequence lysed the host cell.[1] However, contrary to PEST's supposed role in protein degradation, evidence suggests that the PEST-like sequence may regulate LLO production in the cytosol rather than increase degradation of LLO.[1]
Regulation of expression
Listeriolysin O is encoded by the gene hly, which is part of a pathogenicity island called LIPI-1.[1] Transcription of hly, as well as other virulence factors of L. monocytogenes within LIPI-1, is activated by the protein encoded by prfA gene. prfA is thermoregulated, such that translation of prfA maximally occurs at 37°C and is nearly silent at 30°C.[1] Since 37°C is within the range of normal body temperature, PrfA protein, as well as listeriolysin O and other virulence factors regulated by PrfA, is only produced when L. monocytogenes is in a host.
References
External links
- Todar's Online Textbook of Bacteriology - "Listeria monocytogenes and Listeriosis"
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
