Dam- and OxyR-Dependent Phase Variation of
            <i>agn43</i>
            : Essential Elements and Evidence for a New Role of DNA Methylation

Wallecha, Anu; Munster, Vincent J.; Correnti, Jason; Chan, Teresa W.; Woude, Marjan W. van der

doi:10.1128/jb.184.12.3338-3347.2002

Cited by 100 publications

(93 citation statements)

References 44 publications

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“…This plasmid contains the E. coli dam gene cloned directly downstream of the IPTG-inducible lacZ promoter. Overexpression of the Dam methylase after IPTG induction results in methylation at the GATC sites located within the flu gene promoter and this prevents repression by OxyR (Haagmans & van der Woude, 2000;Wallecha et al, 2002). In E. coli MG1655 transformed with pFCH2235, motility was completely ablated, in contrast to the rapid motility of MG1655 (Fig.…”

Section: Enhanced Ag43 Expression Through Dam Methylation Impairs Motmentioning

confidence: 82%

Antigen-43-mediated autoaggregation impairs motility in Escherichia coli

2006

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Functional interaction between bacterial surface-displayed autoaggregation proteins such as antigen 43 (Ag43) of Escherichia coli and motility organelles such as flagella has not previously been described. Here, it has been demonstrated for the first time that Ag43-mediated aggregation can inhibit bacterial motility. Ag43 overexpression produces a dominant aggregation phenotype that overrides motility in the presence of low levels of flagella. In contrast, induction of an increased flagellation state prevents Ag43-mediated aggregation. This phenomenon was observed in naturally occurring subpopulations of E. coli as phase variants expressing and not expressing Ag43 revealed contrasting motility phenotypes. The effects were shown to be part of a general mechanism because other short adhesins capable of mediating autoaggregation (AIDA-I and TibA) also impaired motility. These novel insights into the function of bacterial autoaggregation proteins suggest that a balance between these two systems, i.e. autoaggregation and flagellation, influences motility. INTRODUCTIONThe ability of bacteria to colonize and cause infection is often linked to the expression of specific surface structures. Examples include fimbriae that mediate attachment, flagella that mediate motility, aggregation factors that mediate cell clumping, and a capsule, which provides protection against phagocytosis and host defences. Although the function of these surface structures is often antagonistic, very little is understood regarding the molecular interactions that contribute to their contrasting phenotypes.Antigen 43 (Ag43) is an autotransporter (AT) protein of Escherichia coli that promotes bacterial cell-to-cell aggregation (Diderichsen, 1980;Hasman et al., 1999;Henderson & Owen, 1999;Owen, 1983). It can be expressed on the E. coli cell surface in very high numbers (up to 50 000 copies per cell), resulting in a characteristic frizzy colony morphology (Hasman et al., 2000;Henderson & Owen, 1999;Owen, 1992). Ag43-mediated aggregation is a distinct phenotype that can be visualized macroscopically as flocculation and settling of cells in static liquid suspensions. The protein belongs to the AIDA group of AT proteins and exhibits a high degree of homology to several other members of the AT protein family, namely the AIDA-I adhesin involved in diffuse adherence of enteropathogenic E. coli and the TibA adhesin of enterotoxigenic E. coli (Sherlock et al., 2004(Sherlock et al., , 2005. Ag43 is cleaved into two subunits (a and b), each constituting roughly half of the protein. The b subunit is believed to be an outer-membrane pore-forming component through which Ag43 a gains access to the bacterial surface. The a subunit, on the other hand, remains attached to the bacterial cell surface via interactions with the b subunit (Henderson et al., 2004). The expression of Ag43 is phase-variable with switching rates of~10 23 per cell per generation due to the concerted actions of Dam methylase (positive regulation) and OxyR (negative regulation) (Henderson & Owen,...

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Section: Enhanced Ag43 Expression Through Dam Methylation Impairs Motmentioning

confidence: 82%

Antigen-43-mediated autoaggregation impairs motility in Escherichia coli

2006

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“…OxyR induces the expression of virulence factors that allow pathogens to evade host innate immunity (74,90), while PerR has been shown to directly regulate an extracellular virulence factor (mitogen factor 3) in Streptococcus pyogenes (117). Other clinically relevant processes, such as biofilm formation (99,119) and the oxidation state-independent regulation of several epigenetically controlled promoters determining phase variation (9,113,114), are also regulated by OxyR.…”

Section: Role Of Oxyr Perr and Ohrr In Virulencementioning

confidence: 99%

Peroxide‐Sensing Transcriptional Regulators in Bacteria

Dubbs

Mongkolsuk

2016

Stress and Environmental Regulation of Gene Expression and Adaptation in Bacteria

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The ability to maintain intracellular concentrations of toxic reactive oxygen species (ROS) within safe limits is essential for all aerobic life forms. In bacteria, as well as other organisms, ROS are produced during the normal course of aerobic metabolism, necessitating the constitutive expression of ROS scavenging systems. However, bacteria can also experience transient high-level exposure to ROS derived either from external sources, such as the host defense response, or as a secondary effect of other seemingly unrelated environmental stresses. Consequently, transcriptional regulators have evolved to sense the levels of ROS and coordinate the appropriate oxidative stress response. Three well-studied examples of these are the peroxide responsive regulators OxyR, PerR, and OhrR. OxyR and PerR are sensors of primarily H 2 O 2 , while OhrR senses organic peroxide (ROOH) and sodium hypochlorite (NaOCl). OxyR and OhrR sense oxidants by means of the reversible oxidation of specific cysteine residues. In contrast, PerR senses H 2 O 2 via the Fe-catalyzed oxidation of histidine residues. These transcription regulators also influence complex biological phenomena, such as biofilm formation, the evasion of host immune responses, and antibiotic resistance via the direct regulation of specific proteins.

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“…Based on these observations, it was proposed that the Ag43 phase switch is controlled by competition between OxyR and Dam for binding and methylation within the agn43 regulatory region. Methylation of any two of the three agn43 regulatory GATC sites was sufficient to inhibit binding of OxyR in vitro and allow phase variation to occur in vivo (269), although all three sites appear to be required for attaining normal phase variation rates (271). Binding of OxyR protected all GATC sites from methylation (60) and repressed agn43 transcription in vitro (271).…”

Section: Phase-variable Outer Membrane Protein Ag43mentioning

confidence: 99%

“…6A). Transcription of agn43 begins at the "G" of the promoter-distal GATC-I site (269,271) (Fig. 6A).…”

Section: Phase-variable Outer Membrane Protein Ag43mentioning

confidence: 99%

Epigenetic Gene Regulation in the Bacterial World

Casadesús

Low

2006

Microbiol Mol Biol Rev

560

562

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SUMMARY Like many eukaryotes, bacteria make widespread use of postreplicative DNA methylation for the epigenetic control of DNA-protein interactions. Unlike eukaryotes, however, bacteria use DNA adenine methylation (rather than DNA cytosine methylation) as an epigenetic signal. DNA adenine methylation plays roles in the virulence of diverse pathogens of humans and livestock animals, including pathogenic Escherichia coli, Salmonella, Vibrio, Yersinia, Haemophilus, and Brucella. In Alphaproteobacteria, methylation of adenine at GANTC sites by the CcrM methylase regulates the cell cycle and couples gene transcription to DNA replication. In Gammaproteobacteria, adenine methylation at GATC sites by the Dam methylase provides signals for DNA replication, chromosome segregation, mismatch repair, packaging of bacteriophage genomes, transposase activity, and regulation of gene expression. Transcriptional repression by Dam methylation appears to be more common than transcriptional activation. Certain promoters are active only during the hemimethylation interval that follows DNA replication; repression is restored when the newly synthesized DNA strand is methylated. In the E. coli genome, however, methylation of specific GATC sites can be blocked by cognate DNA binding proteins. Blockage of GATC methylation beyond cell division permits transmission of DNA methylation patterns to daughter cells and can give rise to distinct epigenetic states, each propagated by a positive feedback loop. Switching between alternative DNA methylation patterns can split clonal bacterial populations into epigenetic lineages in a manner reminiscent of eukaryotic cell differentiation. Inheritance of self-propagating DNA methylation patterns governs phase variation in the E. coli pap operon, the agn43 gene, and other loci encoding virulence-related cell surface functions.

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Dam- and OxyR-Dependent Phase Variation of agn43 : Essential Elements and Evidence for a New Role of DNA Methylation

Cited by 100 publications

References 44 publications

Antigen-43-mediated autoaggregation impairs motility in Escherichia coli

Antigen-43-mediated autoaggregation impairs motility in Escherichia coli

Peroxide‐Sensing Transcriptional Regulators in Bacteria

Epigenetic Gene Regulation in the Bacterial World

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