Anthrax SET Protein

Mujtaba, Shiraz; Winer, Benjamin Y.; Jaganathan, Anbalagan; Patel, Jigneshkumar; Sgobba, Miriam; Schuch, Raymond; Gupta, Yogesh K.; Haider, Shozeb; Wang, Rong; Fischetti, Vincent A.

doi:10.1074/jbc.m113.467696

Cited by 45 publications

(21 citation statements)

References 59 publications

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“…Methylation analysis of randomly selected genetic loci using MeDIP (Methylated DNA Immunoprecipitation) and bisulfite sequencing revealed these changes to be at cytosines present in non-CpG rather than the CpG dinucleotide context. These findings mirror our previous finding where the mycobacterial protein Rv2966c was found to be targeting non-CpG dinucleotides 8 and reiterates the hypothesis that bacteria use non-canonical epigenetic strategies during infection 9 10 11 12 13 .…”

supporting

confidence: 89%

Genome-wide non-CpG methylation of the host genome during M. tuberculosis infection

Sharma

Sowpati

Singh

et al. 2016

Sci Rep

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A mammalian cell utilizes DNA methylation to modulate gene expression in response to environmental changes during development and differentiation. Aberrant DNA methylation changes as a correlate to diseased states like cancer, neurodegenerative conditions and cardiovascular diseases have been documented. Here we show genome-wide DNA methylation changes in macrophages infected with the pathogen M. tuberculosis. Majority of the affected genomic loci were hypermethylated in M. tuberculosis infected THP1 macrophages. Hotspots of differential DNA methylation were enriched in genes involved in immune response and chromatin reorganization. Importantly, DNA methylation changes were observed predominantly for cytosines present in non-CpG dinucleotide context. This observation was consistent with our previous finding that the mycobacterial DNA methyltransferase, Rv2966c, targets non-CpG dinucleotides in the host DNA during M. tuberculosis infection and reiterates the hypothesis that pathogenic bacteria use non-canonical epigenetic strategies during infection.

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supporting

confidence: 89%

Genome-wide non-CpG methylation of the host genome during M. tuberculosis infection

Sharma

Sowpati

Singh

et al. 2016

Sci Rep

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“…These phenotypes are unique to lcpB3 and suggest a direct contribution to the bacterial cell cycle compared, for example, to the small cell phenotype observed upon overexpression of the virulence gene set (59). Both the lcpD and lcpB3 mutants assembled reduced amounts of Sap, the predominant S-layer protein, in their envelope, although the spatial distribution of Sap was not affected.…”

Section: Discussionmentioning

confidence: 93%

LytR-CpsA-Psr Enzymes as Determinants of Bacillus anthracis Secondary Cell Wall Polysaccharide Assembly

et al. 2014

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bBacillus anthracis, the causative agent of anthrax, replicates as chains of vegetative cells by regulating the separation of septal peptidoglycan. Surface (S)-layer proteins and associated proteins (BSLs) function as chain length determinants and bind to the secondary cell wall polysaccharide (SCWP). In this study, we identified the B. anthracis lcpD mutant, which displays increased chain length and S-layer assembly defects due to diminished SCWP attachment to peptidoglycan. In contrast, the B. anthracis lcpB3 variant displayed reduced cell size and chain length, which could be attributed to increased deposition of BSLs. In other bacteria, LytR-CpsA-Psr (LCP) proteins attach wall teichoic acid (WTA) and polysaccharide capsule to peptidoglycan. B. anthracis does not synthesize these polymers, yet its genome encodes six LCP homologues, which, when expressed in S. aureus, promote WTA attachment. We propose a model whereby B. anthracis LCPs promote attachment of SCWP precursors to discrete locations in the peptidoglycan, enabling BSL assembly and regulated separation of septal peptidoglycan. Bacillus anthracis, the causative agent of anthrax, is a sporeforming, Gram-positive bacterium that germinates in host infected tissues and replicates as elongated chains of vegetative forms (1, 2). This unique growth pattern appears to be caused by the regulated separation of septal peptidoglycan, which generates bacterial chains whose mere size precludes clearance by host phagocytes (3-5). The genetic determinants for B. anthracis chain formation are conserved among pathogenic species of the Bacillus cereus group and, as demonstrated with B. cereus G9241, likely contribute to disease pathogenesis (6, 7). Hallmarks of pathogenic Bacillus species are virulence plasmids, pXO-1 and pXO-2 in B. anthracis (8, 9), providing for toxin production and capsulation (10, 11) as well as the chromosomally encoded surface (S)-layer locus (12). Two S-layer proteins of B. anthracis, Sap and EA1, are endowed with S-layer homology (SLH) domains, which retain these proteins in the bacterial envelope by binding to the secondary cell wall polysaccharide (SCWP) (13-15). S-layer protein crystallization domains, responsible for the spontaneous assembly of these polypeptides into a paracrystalline array (16), form a twodimensional lattice that can be thought of as bacterial integument (17)(18)(19).The structural genes of S-layer proteins, sap and eag, are flanked by genes encoding determinants for S-layer protein secretion (secA2 and slaP) (12) or pyruvylation (csaB) (14) as well as acetylation of the SCWP (patA1/2 and patB1/2) (20). CsaB-mediated pyruvylation of the terminal N-acetylmannosamine (ManNAc) of the SCWP (21), with the repeat struc- (22), is a prerequisite for the assembly of S-layer proteins and 22 B. anthracis S-layer-associated proteins (BSLs) (14). PatAB1/2-mediated acetylation of SCWP molecules affects the assembly of EA1 and of some but not all BSLs (20). Recent studies have begun to identify genes for SCWP synthesis, which, unlike py...

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“…Listeria monocytogenes caused rapid global deacetylation of histone H4 and specific deacetylation of histone H3K18 in HeLa cells (Eskandarian et al, 2013). Some bacteria could even produce effector molecules that could directly modulate epigenetic histone marks of the host (Li et al, 2013;Mujtaba et al, 2013;Rolando, Gomez-Valero, & Buchrieser, 2015). One limitation of our study is that we could not determine which type of bacteria play the main role in our model of systemic bacterial infection because sublethal CLP caused poly-bacterial peritonitis.…”

Section: Discussionmentioning

confidence: 96%

Bacteria-induced susceptibility toCandida albicanssuper-infection in mice via monocyte methyltransferase Setdb2

Chen

Zheng

et al. 2018

Cellular Microbiology

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Systemic bacterial infections are prone to secondary Candida albicans super-infection. However, the molecular mechanisms involved remain poorly understood. In this study, a model comprising sublethal cecal ligation and puncture plus C. albicans intravenous injection was applied to mimic the situation in super-infection. Compared with mice without systemic bacterial infection, mice with systemic bacterial infection had lower antifungal gene expression (including Il1b, Tnf, Il6, Ifnb, Ifng, Cxcl1, and Ccr2) in monocytes and less inflammatory monocytes and neutrophils infiltrating into the kidney when challenged with C. albicans. Further, lentivirus-mediated Setdb2-knockout and overexpression experiments verified that Setdb2 levels in monocytes correlated negatively with antifungal gene expression and survival rates. Transcriptional repression was probably achieved by Setdb2 through H3 methylation at lysine 9 in promoter regions of these antifungal genes.

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Anthrax SET Protein

Cited by 45 publications

References 59 publications

Genome-wide non-CpG methylation of the host genome during M. tuberculosis infection

Genome-wide non-CpG methylation of the host genome during M. tuberculosis infection

LytR-CpsA-Psr Enzymes as Determinants of Bacillus anthracis Secondary Cell Wall Polysaccharide Assembly

Bacteria-induced susceptibility toCandida albicanssuper-infection in mice via monocyte methyltransferase Setdb2

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