Integration host factor (IHF) mediates repression of flagella in enteropathogenic and enterohaemorrhagic Escherichia coli

Yona-Nadler, Chen; Umanski, Tatiania; Aizawa, Shin‐Ichi; Friedberg, Devorah; Rosenshine, Ilan

doi:10.1099/mic.0.25970-0

Cited by 50 publications

(43 citation statements)

References 30 publications

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“…Addressing the potential for non-FliC-dependent inflammation is important, since several studies have suggested that EPEC deregulates FliC expression when exposed to culture media and/or epithelial cells. For example, integration host factor was found to repress the expression of flagellin in EPEC and EHEC when grown in DMEM (45). Similarly, studies of other bacterial pathogens suggest that while flagellin expression may occur at early stages of infection, or at specific tissue sites, flagellin expression may be reduced or even absent at later stages of infection, as was recently described for Salmonella enterica serovar Typhimurium (11).…”

Section: Discussionmentioning

confidence: 86%

Flagellin-Dependent and -Independent Inflammatory Responses following Infection by EnteropathogenicEscherichia coliandCitrobacter rodentium

Khan

Bouzari

et al. 2008

Infect Immun

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Enteropathogenic Escherichia coli (EPEC) and the murine pathogen Citrobacter rodentium belong to the attaching and effacing (A/E) family of bacterial pathogens. These noninvasive bacteria infect intestinal enterocytes using a type 3 secretion system (T3SS), leading to diarrheal disease and intestinal inflammation. While flagellin, the secreted product of the EPEC fliC gene, causes the release of interleukin 8 (IL-8) from epithelial cells, it is unclear whether A/E bacteria also trigger epithelial inflammatory responses that are FliC independent. The aims of this study were to characterize the FliC dependence or independence of epithelial inflammatory responses to direct infection by EPEC or C. rodentium. Following infection of Caco-2 intestinal epithelial cells by wild-type and ⌬fliC EPEC, a rapid activation of several proinflammatory genes, including those encoding IL-8, monocyte chemoattractant protein 1, macrophage inflammatory protein 3␣ (MIP3␣), and ␤-defensin 2, occurred in a FliC-dependent manner. These responses were accompanied by mitogen-activated protein kinase activation, as well as the Toll-like receptor 5 (TLR5)-dependent activation of NF-B. At later infection time points, a subset of these proinflammatory genes (IL-8 and MIP3␣) was also induced in cells infected with ⌬fliC EPEC. The nonmotile A/E pathogen C. rodentium also triggered similar innate responses through a TLR5-independent but partially NF-B-dependent mechanism. Moreover, the EPEC FliC-independent responses were increased in the absence of the locus of enterocyte effacement-encoded T3SS, suggesting that translocated bacterial effectors suppress rather than cause the FliC-independent inflammatory response. Thus, we demonstrate that infection of intestinal epithelial cells by A/E pathogens can trigger an array of proinflammatory responses from epithelial cells through both FliC-dependent and -independent pathways, expanding our understanding of the innate epithelial response to infection by these pathogens.

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Section: Discussionmentioning

confidence: 86%

Flagellin-Dependent and -Independent Inflammatory Responses following Infection by EnteropathogenicEscherichia coliandCitrobacter rodentium

Khan

Bouzari

et al. 2008

Infect Immun

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“…This region is 123 bp in size, between nucleotides Ϫ159 and Ϫ36 relative to the transcription start site (Fig. 1), and contains an IHF-binding site that is required for LEE1 expression (11,34). However, 9F-gfp also contains the putative ler ribosome binding site and a part of the ler coding region, which could interfere with the translation of gfp.…”

Section: Resultsmentioning

confidence: 99%

“…GadX regulates LEE gene expression indirectly by affecting PerC expression (26). The IHF and H-NS regulation of the LEE1 promoter correlates with direct interaction of these proteins with the LEE1 regulatory region (11,32,34). We predict that at least some of the other LEE regulators, including PerC, GrlA, GrlR, Fis, BipA, or quorum-sensing factor, directly regulate the LEE1 promoter by binding to the LEE1 regulatory region.…”

Section: Discussionmentioning

confidence: 99%

Ler Is a Negative Autoregulator of theLEE1Operon in EnteropathogenicEscherichia coli

et al. 2005

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Enteropathogenic Escherichia coli (EPEC) causes severe diarrhea in young children. Essential for colonization of the host intestine is the LEE pathogenicity island, which comprises a cluster of operons encoding a type III secretion system and related proteins. The LEE1 operon encodes Ler, which positively regulates many EPEC virulence genes in the LEE region and elsewhere in the chromosome. We found that Ler acts as a specific autorepressor of LEE1 transcription. We further show that Ler specifically binds upstream of the LEE1 operon in vivo and in vitro. A comparison of the Ler affinities to different DNA regions suggests that the autoregulation mechanism limits the steady-state level of Ler to concentrations that are just sufficient for activation of the LEE2 and LEE3 promoters and probably other LEE promoters. This mechanism may reflect the need of EPEC to balance maximizing the colonization efficiency by increasing the expression of the virulence genes and minimizing the immune response of the host by limiting their expression. In addition, we found that the autoregulation mechanism reduces the cell-to-cell variability in the levels of LEE1 expression. Our findings point to a new negative regulatory circuit that suppresses the noise and optimizes the expression levels of ler and other LEE1 genes.Colonizing enteropathogens compete with the gut flora to gain a foothold in the host tissue by expressing powerful colonization factors. However, to reduce the immune response of the host, the pathogen should minimize the expression of the colonization factors. To resolve this dilemma, pathogens evolved regulatory mechanisms that optimize the expression levels and timing, thus maintaining expression of just enough colonization factors and only when needed. Another layer of complexity is added when the colonization is dependent on the assembly of organelles like the type III secretion systems (TTSS), which are composed of ϳ30 different proteins of various relative amounts and encoded by several operons. In these cases, an orderly expression program is required for efficient assembly of the organelle.Enteropathogenic Escherichia coli (EPEC) causes severe diarrhea in young children. It employs the TTSS as a molecular syringe to inject a battery of toxic or colonization proteins into the membrane and cytoplasm of infected host cells (4). The TTSS and some of the effectors are encoded by a 35.6-kbp pathogenicity island, termed the locus for enterocyte effacement (LEE). The LEE consists of 41 genes, organized in five major operons (LEE1 to LEE5) and several additional transcriptional units (10,19). Ler, an H-NS paralog, encoded by the first gene of the LEE1 operon, is a key regulator of the LEE regulon, positively regulating expression of LEE2, LEE3, LEE4, LEE5, espG, and map (11,19,24,30). The regulation of ler (LEE1 operon) is complex and involves many factors, including H-NS, integration host factor (IHF), Fis, PerC, BipA, GrlA, GrlR, GadX, and quorum sensing (2,7,11,13,14,17,19,26,28,30,32). Most of these factors appe...

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“…Many of these environmental influences affect the transcription of flagellar genes and control in particular the expression of the master regulator, FlhDC. The regulators of the flhDC operon include cyclic AMP (cAMP)-cAMP receptor protein (CRP), H-NS (4), OmpR (2), LrhA (5), integration host factor (IHF) (2,6), RpoN (7), and Fur (8). Other regulators affect cell motility by controlling fliA expression.…”

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confidence: 99%

Repression of Flagellar Genes in Exponential Phase by CsgD and CpxR, Two Crucial Modulators of Escherichia coli Biofilm Formation

et al. 2014

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e Escherichia coli adapts its lifestyle to the variations of environmental growth conditions, swapping between swimming motility or biofilm formation. The stationary-phase sigma factor RpoS is an important regulator of this switch, since it stimulates adhesion and represses flagellar biosynthesis. By measuring the dynamics of gene expression, we show that RpoS inhibits the transcription of the flagellar sigma factor, FliA, in exponential growth phase. RpoS also partially controls the expression of CsgD and CpxR, two transcription factors important for bacterial adhesion. We demonstrate that these two regulators repress the transcription of fliA, flgM, and tar and that this regulation is dependent on the growth medium. CsgD binds to the flgM and fliA promoters around their ؊10 promoter element, strongly suggesting direct repression. We show that CsgD and CpxR also affect the expression of other known modulators of cell motility. We propose an updated structure of the regulatory network controlling the choice between adhesion and motility.M icroorganisms adapt to changes in their environment in many different ways. Among others, they adjust gene expression, modify their metabolism, and change their surface properties by displaying particular surface proteins. The latter phenomenon is directly linked to the choice of a particular "lifestyle," adhesion (biofilm formation) or motility (planktonic growth). In Escherichia coli, expression of flagella at the cell surface predestines the cell for motility. More than 50 genes are involved in the synthesis of flagella. These genes are classified into three groups according to their temporal expression sequence. The master regulator of flagellar synthesis, FlhDC, is expressed first, and the corresponding genes constitute the class 1 flagellar operon. FlhDC activates the expression of class 2 genes, encoding the inner part of the flagellum as well as the flagellar sigma factor FliA ( 28 or F ) and the FlgM protein (anti-28 ). The class 3 genes are transcribed by 28 -RNA polymerase (RNAP) and encode the outer components of the flagellum as well as chemotaxis proteins (for a review, see reference 1).Flagellar synthesis is tightly controlled by several environmental conditions, including osmolarity (2) and temperature (3). Many of these environmental influences affect the transcription of flagellar genes and control in particular the expression of the master regulator, FlhDC. The regulators of the flhDC operon include cyclic AMP (cAMP)-cAMP receptor protein (CRP), H-NS (4), OmpR (2), LrhA (5), integration host factor (IHF) (2, 6), RpoN (7), and Fur (8). Other regulators affect cell motility by controlling fliA expression. These factors include NsrR (9), signaling molecules such as cyclic diguanylic acid (c-di-GMP) (reviewed in reference 10), the alarmone polyphosphate guanosine [(p)ppGpp] (11), and quorum-sensing molecules such as autoinducer-2 (AI-2) (12)(13)(14).Transcriptomic data show that the stationary sigma factor RpoS ( 38 ) represses the transcription of flagellar gene...

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Integration host factor (IHF) mediates repression of flagella in enteropathogenic and enterohaemorrhagic Escherichia coli

Cited by 50 publications

References 30 publications

Flagellin-Dependent and -Independent Inflammatory Responses following Infection by EnteropathogenicEscherichia coliandCitrobacter rodentium

Flagellin-Dependent and -Independent Inflammatory Responses following Infection by EnteropathogenicEscherichia coliandCitrobacter rodentium

Ler Is a Negative Autoregulator of theLEE1Operon in EnteropathogenicEscherichia coli

Repression of Flagellar Genes in Exponential Phase by CsgD and CpxR, Two Crucial Modulators of Escherichia coli Biofilm Formation

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