title: Altered Ca(2+) regulation of Yop secretion in Yersinia enterocolitica after DNA adenine methyltransferase overproduction is mediated by Clp-dependent degradation of LcrG.
abstract: DNA methylation by the DNA adenine methyltransferase (Dam) interferes with the coordinated expression of virulence functions in an increasing number of pathogens. While analyzing the effect of Dam on the virulence of the human pathogen Yersinia enterocolitica, we observed type III secretion of Yop effector proteins under nonpermissive conditions. Dam alters the Ca(2+) regulation of Yop secretion but does not affect the temperature regulation of Yop/Ysc expression. The phenotype is different from that of classical "Ca(2+)-blind" mutants of Yersinia, as Dam-overproducing (Dam(OP)) strains still translocate Yops polarly into eukaryotic cells. Although transcription of the lcrGV and yopN-tyeA operons is slightly upregulated, LcrG is absent from lysates of Dam(OP) bacteria, while the amounts of YopN and TyeA are not changed. We present evidence that clpXP expression increases after Dam overproduction and that the ClpP protease then degrades LcrG, thereby releasing a block in type III secretion. This is the first example of posttranslational regulation of type III secretion by the Clp protease and adds a new flavor to the complex regulatory mechanisms underlying the controlled release of effector proteins from bacterial cells.
authors.affiliation: ZMBE, Institut für Infektiologie, von-Esmarch-Str. 56, 48149 Münster, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Fälker
authors.forename: M Alexander
authors.initials: MA
authors.lastname: Schmidt
authors.forename: Gerhard
authors.initials: G
authors.lastname: Heusipp
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000096:biosynthesis; D004591:Electrophoresis, Polyacrylamide Gel; D049071:Endopeptidase Clp / Q000096:biosynthesis*; D015870:Gene Expression; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D052899:Pore Forming Cytotoxic Proteins; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000096:biosynthesis* / Q000235:genetics; D037521:Virulence Factors / Q000096:biosynthesis; D015008:Yersinia enterocolitica / Q000235:genetics / Q000378:metabolism*; D001616:beta-Galactosidase / Q000032:analysis / Q000235:genetics
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C088009:LcrG protein, Yersinia; D052899:Pore Forming Cytotoxic Proteins; D037521:Virulence Factors; C116117:YopT protein, Yersinia; C063239:yopE protein, Yersinia; C060772:yopM protein, Yersinia; C058693:Dam methyltransferase; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia; D001616:beta-Galactosidase; D049071:Endopeptidase Clp; D003546:Cysteine Endopeptidases; D002118:Calcium