A bacterial pore-forming toxin forms aggregates in cells that resemble those associated with neurodegenerative diseases.
Listeria monocytogenes is a bacterial, facultative intracellular pathogen, which secretes a pore-forming toxin called listeriolysin O (LLO). LLO mediates the dissolution of the phagosomal membrane allowing L. monocytogenes to reach and grow in the host cytosolic compartment. In this study we report the localization of LLO secreted in infected cells. We described that LLO (i) forms small perinuclear aggregates, (ii) accumulates in large autophagosome-like structures and (iii) sequesters to large protein aggregates. The formation of protein aggregates required full LLO activity. Further characterization of protein aggregates indicated that they not only contained the active form of LLO but also polyubiquitinated proteins and p62, which are both common components of protein aggregates found in neurological diseases. Hence, a protein of bacterial origin could potentially follow the same fate as a toxic protein associated with neurodegenerative disease.
Viala
Julie P M
JP
Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Mochegova
Sofia N
SN
Meyer-Morse
Nicole
N
Portnoy
Daniel A
DA
D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006460:Hemolysin Proteins / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008856:Microscopy, Fluorescence; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism
D001427:Bacterial Toxins; C490981:Gtf2h1 protein, mouse; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D014157:Transcription Factors; D014452:Ubiquitins; D051758:Transcription Factor TFIIH; C038705:hlyA protein, Listeria monocytogenes