title: Regulated translation of listeriolysin O controls virulence of Listeria monocytogenes.
abstract: Listeria monocytogenes is an intracytosolic bacterial pathogen that escapes from the phagosome using a secreted cytolysin, listeriolysin O (LLO). In the host cytosol, LLO activity is minimized to prevent pore formation in the host plasma membrane; premature lysis of the infected host cell exposes the bacteria to extracellular immune defences of the host and is detrimental to infection. Here we identified nucleotide substitutions in the coding sequence of the LLO gene (hly) that did not alter the protein sequence, yet caused over-production of LLO, cytotoxicity and loss of virulence. These phenotypes were independent of the promoter and, under conditions in which the mutants produced more LLO protein than wild type, levels of hly mRNA were similar. Finally, negative regulation of LLO was maintained even when bacteria were engineered to produce elevated levels of the wild-type hly transcript. Together, our data demonstrate that translational regulation of LLO is critical for L. monocytogenes pathogenesis.
authors.affiliation: Graduate Group in Microbiology, University of California, Berkeley, CA 94720-3202, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Schnupf
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hofmann
authors.forename: Julie
authors.initials: J
authors.lastname: Norseen
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Glomski
authors.forename: Hal
authors.initials: H
authors.lastname: Schwartzstein
authors.forename: Amy L
authors.initials: AL
authors.lastname: Decatur
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics; D016923:Cell Death; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D003600:Cytosol / Q000382:microbiology; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D006460:Hemolysin Proteins; D008089:Listeria monocytogenes / Q000737:chemistry / Q000378:metabolism / Q000472:pathogenicity*; D008088:Listeriosis / Q000209:etiology*; D008264:Macrophages / Q000166:cytology / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016296:Mutagenesis; D009841:Oligonucleotides; D010641:Phenotype; D014176:Protein Biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014774:Virulence
chemical_list: D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D009841:Oligonucleotides; C038705:hlyA protein, Listeria monocytogenes