Dam and its role in pathogenicity of Salmonella enterica.
ABSTRACT Dam methylation is an essential factor involved in the virulence of an increasing number of bacterial pathogens including Salmonella enterica. Lack of Dam methylation causes severe attenuation in animal models. It has been proposed that dysregulation of Dam activity is potentially a general strategy for the generation of vaccines against bacterial pathogens. In this review, we focus our attention on the role of methylation by Dam protein in regulating bacterial gene expression and virulence in Salmonella enterica.
Full-textDOI: · Available from: Sebastian Sarnacki, Jun 02, 2015
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ABSTRACT: Recent studies have revealed that bacterial protein methylation is a widespread post-translational modification that is required for virulence in selected pathogenic bacteria. In particular, altered methylation of outer-membrane proteins has been shown to modulate the effectiveness of the host immune response. In this study, 2D gel electrophoresis combined with MALDI-TOF MS identified a Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 protein, corresponding to ORF LIC11848, which undergoes extensive and differential methylation of glutamic acid residues. Immunofluorescence microscopy implicated LIC11848 as a surface-exposed outer-membrane protein, prompting the designation OmpL32. Indirect immunofluorescence microscopy of golden Syrian hamster liver and kidney sections revealed expression of OmpL32 during colonization of these organs. Identification of methylated surface-exposed outer-membrane proteins, such as OmpL32, provides a foundation for delineating the role of this post-translational modification in leptospiral virulence.Microbiology 12/2011; 158(Pt 3):622-35. DOI:10.1099/mic.0.054767-0 · 2.84 Impact Factor
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ABSTRACT: DNA methylation regulates gene expression in many organisms. In eukaryotes, DNA methylation is associated with gene repression, while it exerts both activating and repressive effects in the Proteobacteria through largely locus-specific mechanisms. Here, we identify a critical DNA methyltransferase in M. tuberculosis, which we term MamA. MamA creates N(6)-methyladenine in a six base pair recognition sequence present in approximately 2,000 copies on each strand of the genome. Loss of MamA reduces the expression of a number of genes. Each has a MamA site located at a conserved position relative to the sigma factor -10 binding site and transcriptional start site, suggesting that MamA modulates their expression through a shared, not locus-specific, mechanism. While strains lacking MamA grow normally in vitro, they are attenuated in hypoxic conditions, suggesting that methylation promotes survival in discrete host microenvironments. Interestingly, we demonstrate strikingly different patterns of DNA methyltransferase activity in different lineages of M. tuberculosis, which have been associated with preferences for distinct host environments and different disease courses in humans. Thus, MamA is the major functional adenine methyltransferase in M. tuberculosis strains of the Euro-American lineage while strains of the Beijing lineage harbor a point mutation that largely inactivates MamA but possess a second functional DNA methyltransferase. Our results indicate that MamA influences gene expression in M. tuberculosis and plays an important but strain-specific role in fitness during hypoxia.PLoS Pathogens 07/2013; 9(7):e1003419. DOI:10.1371/journal.ppat.1003419 · 8.06 Impact Factor
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ABSTRACT: Background Bacterial insertion sequences (IS) of IS200/IS605 and IS607 family often encode a transposase (TnpA) and a protein of unknown function, TnpB. Results Here we report two groups of TnpB-like proteins (Fanzor1 and Fanzor2) that are widespread in diverse eukaryotic transposable elements (TEs), and in large double-stranded DNA (dsDNA) viruses infecting eukaryotes. Fanzor and TnpB proteins share the same conserved amino acid motif in their C-terminal half regions: D-X(125, 275)-[TS]-[TS]-X-X-[C4 zinc finger]-X(5,50)-RD, but are highly variable in their N-terminal regions. Fanzor1 proteins are frequently captured by DNA transposons from different superfamilies including Helitron, Mariner, IS4-like, Sola and MuDr. In contrast, Fanzor2 proteins appear only in some IS607-type elements. We also analyze a new Helitron2 group from the Helitron superfamily, which contains elements with hairpin structures on both ends. Non-autonomous Helitron2 elements (CRe-1, 2, 3) in the genome of green alga Chlamydomonas reinhardtii are flanked by target site duplications (TSDs) of variable length (approximately 7 to 19 bp). Conclusions The phylogeny and distribution of the TnpB/Fanzor proteins indicate that they may be disseminated among eukaryotic species by viruses. We hypothesize that TnpB/Fanzor proteins may act as methyltransferases.Mobile DNA 04/2013; 4(1):12. DOI:10.1186/1759-8753-4-12 · 2.43 Impact Factor