The GrlR-GrlA Regulatory System Coordinately Controls the Expression of Flagellar and LEE-Encoded Type III Protein Secretion Systems in Enterohemorrhagic<i>Escherichia coli</i>

Iyoda, Sunao; Koizumi, Nobuo; Satou, Hitomi; Lu, Yan; Saitoh, Takehito; Ohnishi, Makoto; Watanabe, Haruo

doi:10.1128/jb.00352-06

Cited by 91 publications

(122 citation statements)

References 81 publications

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“…Mucin on agar plates repressed motility, and transcriptome analysis and quantitative PCR confirmed these data (27). In addition, the GrlA regulator, expressed from the LEE, decreased flagella biosynthesis by downregulating fliC and flhDC (28) (Fig. 2).…”

Section: Motilitysupporting

confidence: 52%

“…4). The GrlRA regulators constitute a complicated feedback loop whereby GrlA directly activates ler expression, and GrlR acts posttranslationally to reduce the cellular quantity of the GrlA protein (28,61,64,65). Once expressed, Ler, in turn, acts as an H-NS antisilencer to increase the expression of LEE2, LEE3, LEE4, and LEE5 operons (Fig.…”

Section: Figure 4 Stimulation Of Lee and Non-lee Effector Molecules Rmentioning

confidence: 99%

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Enterohemorrhagic Escherichia coli Virulence Gene Regulation

Mellies

Lorenzen

2014

Microbiol Spectr

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Coordinated expression of enterohemorrhagic Escherichia coli virulence genes enables the bacterium to cause hemorrhagic colitis and the complication known as hemolytic-uremic syndrome. Horizontally acquired genes and those common to E. coli contribute to the disease process, and increased virulence gene expression is correlated with more severe disease in humans. Researchers have gained considerable knowledge about how the type III secretion system, secreted effectors, adhesin molecules, and the Shiga toxins are regulated by environmental signals and multiple genetic pathways. Also emergent from the data is an understanding of how enterohemorrhagic E. coli regulates response to acid stress, the role of flagellar motility, and how passage through the human host and bovine intestinal tract causes disease and supports carriage in the cattle reservoir, respectively. Particularly exciting areas of discovery include data suggesting how expression of the myriad effectors is coordinately regulated with their cognate type III secretion system and how virulence is correlated with bacterial metabolism and gut physiology.As a species, Escherichia coli is highly successful, adapting to inhabit the lower intestine of warm-blooded animals. Commensal E. coli, part of the normal biota, resides harmlessly in the gut, producing vitamin K. However, E. coli also causes three types of disease in humans: urinary tract infections, sepsis in newborns, and diarrheal disease. Enterohemorrhagic E. coli (EHEC) plays a prominent role in the third type of illness. It has been estimated that, for the pan genome of E. coli, the nonpathogenic and pathogenic strains only contain a core set of genes comprising approximately 20% of any one genome (1, 2). Much of the horizontally acquired genetic information is clustered within genomic islands in pathogens. As for EHEC, this has allowed the organism to not only attach and colonize the large intestine of humans and other animals, to outcompete commensal E. coli and other bacteria at the site of infection, but also to cause serious disease.Horizontally acquired genetic information in EHEC results in evolution into a specific pathotype-genotype dictates phenotype. How this genetic information is controlled is of equal importance for the success and virulence of the organism. Indeed, investigated differences in virulence gene regulation in two distinct EHEC isolate lineages, clade 8 and clade 2. A clade is a group of EHEC isolates with one ancestor and all its descendants. Eight clades of E. coli O157 isolates were defined by single nucleotide polymorphism (SNP) analyses, where clade 8 was a group of hypervirulent bacteria compared to the other seven clades (4). By examining multiple strains per lineage, the investigators found increased expression of horizontally acquired virulence genes in clade 8 versus clade 2. Genes expressed to higher levels in clade 8, which is associated with a greater number of cases of E. coli hemorrhagic

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Section: Motilitysupporting

confidence: 52%

Section: Figure 4 Stimulation Of Lee and Non-lee Effector Molecules Rmentioning

confidence: 99%

Enterohemorrhagic Escherichia coli Virulence Gene Regulation

Mellies

Lorenzen

2014

Microbiol Spectr

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“…On the other hand, bacterial cells expressing extracellular flagellar filaments have a disadvantage because flagellin, the fliC-encoded major subunit of flagella, is highly antigenic and activates toll-like receptor 5, leading to a pro-inflammatory response in the host (Hayashi et al, 2001a). It is also known that constitutive expression of flhDC greatly decreases efficient adhesion in EHEC (Iyoda et al, 2006). Thus, flagellar expression must be strictly and properly regulated in each phase of infection.…”

Section: A Multicopy Plasmid Carrying the Esr41 Gene Increased Cell Mmentioning

confidence: 99%

“…Though the most important virulence determinant responsible for severe illness is Shiga toxin, other virulence factors, including the Type 3 (T3) secretion system and T3 effectors, also contribute to the EHEC pathogenicity Frankel et al, 1998;Nataro and Kaper, 1998). The expression of these virulence factors is strictly regulated through a complicated and only partially understood regulatory network (Elliott et al, 2000;Honda et al, 2009;Iyoda and Watanabe, 2004;Iyoda et al, 2006;Sperandio et al, 2003). Despite the detailed knowledge of sRNAs/Hfq-mediated regulation in the E. coli K-12, little is known about the contribution of sRNA to regulation in EHEC.…”

Section: Introductionmentioning

confidence: 99%

A novel small regulatory RNA enhances cell motility in enterohemorrhagic Escherichia coli

Sudo

Soma

Muto

et al. 2014

J. Gen. Appl. Microbiol.

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Small regulatory RNAs (sRNAs) are conserved among a wide range of bacteria. They modulate the translational efficiency of target mRNAs through base-pairing with the help of RNA chaperone Hfq. The present study identified a novel sRNA, Esr41 (enterohemorrhagic Escherichia coli O157 small RNA #41), from an intergenic region of an enterohemorrhagic E. coli (EHEC) O157:H7 Sakai-specific sequence that is not present in the nonpathogenic E. coli K-12. Esr41 was detected as an RNA molecule approximately 70 nucleotides long with a 3 GC-rich palindrome sequence followed by a long poly(U), which is a characteristic of rho-independent terminators and is also a structural feature required for the action of Hfq. EHEC O157 harboring a multicopy plasmid carrying the esr41 gene increased cell motility and the expression of fliC, a gene encoding a major flagellar component. These results indicate that Esr41 stimulates fliC expression in EHEC O157. Furthermore, the increase in cell motility induced by Esr41 was also observed in the E. coli K-12, suggesting that target genes controlled by Esr41 are present in both EHEC O157 and K-12.Key words cell motility; EHEC O157 : H7 Sakai; flagella; small regulatory RNA IntroductionSmall regulatory RNAs (sRNAs) play crucial roles in bacterial stress responses and virulence (Gottesman, 2004;Papenfort and Vogel, 2010;Waters and Storz, 2009). Many sRNAs are induced under specific physiological conditions and control the expression of target genes, primarily at the post-transcriptional levels (Gottesman, 2004;Wassarman, 2002). sRNAs are classified as cis-acting sRNAs or transacting sRNAs. Cis-acting sRNAs are encoded on the strand opposite to the sense strand of the target gene and regulate the target gene expression by perfect base-pairing with its mRNA (Kawano et al., 2005). Trans-acting sRNAs are usually encoded in a different region from that of the target genes and regulate the expression of the target genes by partial base-pairing with their mRNAs. One major class of sRNA binds to RNA chaperone Hfq, which facilitates base-pairing between sRNA and the target mRNA to regulate its translation, mostly negatively but also positively in some cases (Aiba, 2007;Vogel and Luisi, 2011).A comprehensive identification of sRNA has been performed in many bacteria, such as Escherichia coli and None of the authors of this manuscript has any financial or personal relationship with other people or organizations that could inappropriately influence their work.

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“…Ler further activates the LEE-encoded regulators GrlA and GrlR, which in turn activate and repress ler transcription, respectively (5)(6)(7)(8)(9)(10). Numerous non-LEE-encoded regulators also converge on ler and grlA promoters to coordinate LEE-dependent colonization with environmental/physiological cues (11)(12)(13)(14)(15)(16)(17)(18)(19).…”

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confidence: 99%

Global Regulator of Virulence A (GrvA) Coordinates Expression of Discrete Pathogenic Mechanisms in Enterohemorrhagic Escherichia coli through Interactions with GadW-GadE

et al. 2016

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Global regulator of virulence A (GrvA) is a ToxR-family transcriptional regulator that activates locus of enterocyte effacement (LEE)-dependent adherence in enterohemorrhagic Escherichia coli (EHEC). LEE activation by GrvA requires the Rcs phosphorelay response regulator RcsB and is sensitive to physiologically relevant concentrations of bicarbonate, a known stimulant of virulence systems in intestinal pathogens. This study determines the genomic scale of GrvA-dependent regulation and uncovers details of the molecular mechanism underlying GrvA-dependent regulation of pathogenic mechanisms in EHEC. In a grvA-null background of EHEC strain TW14359, RNA sequencing analysis revealed the altered expression of over 700 genes, including the downregulation of LEE-and non-LEE-encoded effectors and the upregulation of genes for glutamate-dependent acid resistance (GDAR). Upregulation of GDAR genes corresponded with a marked increase in acid resistance. GrvA-dependent regulation of GDAR and the LEE required gadE, the central activator of GDAR genes and a direct repressor of the LEE. Control of gadE by GrvA was further determined to occur through downregulation of the gadE activator GadW. This interaction of GrvA with GadW-GadE represses the acid resistance phenotype, while it concomitantly activates the LEE-dependent adherence and secretion of immune subversion effectors. The results of this study significantly broaden the scope of GrvA-dependent regulation and its role in EHEC pathogenesis. IMPORTANCEEnterohemorrhagic Escherichia coli (EHEC) is an intestinal human pathogen causing acute hemorrhagic colitis and life-threatening hemolytic-uremic syndrome. For successful transmission and gut colonization, EHEC relies on the glutamate-dependent acid resistance (GDAR) system and a type III secretion apparatus, encoded on the LEE pathogenicity island. This study investigates the mechanism whereby the DNA-binding regulator GrvA coordinates activation of the LEE with repression of GDAR. Investigating how these systems are regulated leads to an understanding of pathogenic behavior and novel strategies aimed at disease prevention and control.

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The GrlR-GrlA Regulatory System Coordinately Controls the Expression of Flagellar and LEE-Encoded Type III Protein Secretion Systems in EnterohemorrhagicEscherichia coli

Cited by 91 publications

References 81 publications

Enterohemorrhagic Escherichia coli Virulence Gene Regulation

Enterohemorrhagic Escherichia coli Virulence Gene Regulation

A novel small regulatory RNA enhances cell motility in enterohemorrhagic Escherichia coli

Global Regulator of Virulence A (GrvA) Coordinates Expression of Discrete Pathogenic Mechanisms in Enterohemorrhagic Escherichia coli through Interactions with GadW-GadE

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