A PEST-like sequence in listeriolysin O essential for Listeria monocytogenes pathogenicity.
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.
Decatur
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Department of Molecular and Cell Biology, Division of Infectious Diseases, School of Public Health, University of California, Berkeley, CA 94720, USA.
Portnoy
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DA
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D006460:Hemolysin Proteins; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008089:Listeria monocytogenes / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D008088:Listeriosis / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D010588:Phagosomes / Q000382:microbiology; D010766:Phosphorylation; D017384:Sequence Deletion; D014774:Virulence
D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; C020452:Clostridium perfringens theta-toxin; D007770:L-Lactate Dehydrogenase; C038705:hlyA protein, Listeria monocytogenes