Control freaks—signals and cues governing the regulation of virulence in attaching and effacing pathogens

Turner, Natasha C. A.; Connolly, James P. R.; Roe, Andrew J.

doi:10.1042/bst20180546

Cited by 24 publications

(28 citation statements)

References 94 publications

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“…The gastrointestinal environment is complex and profoundly impacted by the membership of the resident microbiota, host genetics, diet, and enteric diseases. Bacterial enteric pathogens evolved intricate regulatory systems to integrate multiple cues toward exquisite control of the expression of their virulence repertoire (3,27). The significance of this molecular circuitry is conspicuous in EHEC, which colonizes the densely populated colon with a remarkable low infectious dose (50 CFUs) (1,3).…”

Section: Discussionmentioning

confidence: 99%

“…EHEC integrates metabolism and virulence at multiple levels, with nutrients also serving as signals to modulate virulence gene expression (3,4). We previously performed a comprehensive HTS screen to map metabolic pathways that impacted virulence expression (with emphasis on LEE gene expression) in EHEC (4).…”

Section: Discussionmentioning

confidence: 99%

“…1A). Transcription of ler is controlled by several host and microbiota-derived signals such as epinephrine, norepinephrine, succinate, fucose, serine, cysteine, and ethanolamine among others (3).…”

mentioning

confidence: 99%

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l -Arginine sensing regulates virulence gene expression and disease progression in enteric pathogens

Menezes‐Garcia

Kumar

Zhu

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Microbiota, host and dietary metabolites/signals compose the rich gut chemical environment, which profoundly impacts virulence of enteric pathogens. EnterohemorrhagicEscherichia coli(EHEC) engages a syringe-like machinery named type-III secretion system (T3SS) to inject effectors within host cells that lead to intestinal colonization and disease. We previously conducted a high-throughput screen to identify metabolic pathways that affect T3SS expression. Here we show that in the presence of arginine, the arginine sensor ArgR, identified through this screen, directly activates expression of the genes encoding the T3SS. Exogenously added arginine induces EHEC virulence gene expression in vitro. Congruently, a mutant deficient in arginine transport (ΔartP) had decreased virulence gene expression. ArgR also augments murine disease caused byCitrobacter rodentium, which is a murine pathogen extensively employed as a surrogate animal model for EHEC. The source of arginine sensed byC. rodentiumis not dietary. At the peak ofC. rodentiuminfection, increased arginine concentration in the colon correlated with down-regulation of the host SLC7A2 transporter. This increase in the concentration of colonic arginine promotes virulence gene expression inC. rodentium. Arginine is an important modulator of the host immune response to pathogens. Here we add that arginine also directly impacts bacterial virulence. These findings suggest that a delicate balance between host and pathogen responses to arginine occur during disease progression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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l -Arginine sensing regulates virulence gene expression and disease progression in enteric pathogens

Menezes‐Garcia

Kumar

Zhu

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…The LEE is undoubtedly the most investigated PAI in DEC, and readers are referred to recent reviews solely dedicated to this PAI for detailed information (Kirsch et al, 2004;Parham et al, 2005a;Schmidt, 2010;Stevens and Frankel, 2014;Connolly et al, 2015;Franzin and Sircili, 2015;Kendall, 2016;Furniss and Clements, 2018;Turner et al, 2019). The presence of the LEE is the hallmark of EPEC, but it is also found in tEHEC (McDaniel et al, 1995;McDaniel and Kaper, 1997).…”

Section: Lee Paimentioning

confidence: 99%

Pathogenicity Factors of Genomic Islands in Intestinal and Extraintestinal Escherichia coli

Desvaux¹,

Dalmasso²,

Beyrouthy³

et al. 2020

Front. Microbiol.

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Escherichia coli is a versatile bacterial species that includes both harmless commensal strains and pathogenic strains found in the gastrointestinal tract in humans and warmblooded animals. The growing amount of DNA sequence information generated in the era of "genomics" has helped to increase our understanding of the factors and mechanisms involved in the diversification of this bacterial species. The pathogenic side of E. coli that is afforded through horizontal transfers of genes encoding virulence factors enables this bacterium to become a highly diverse and adapted pathogen that is responsible for intestinal or extraintestinal diseases in humans and animals. Many of the accessory genes acquired by horizontal transfers form syntenic blocks and are recognized as genomic islands (GIs). These genomic regions contribute to the rapid evolution, diversification and adaptation of E. coli variants because they are frequently subject to rearrangements, excision and transfer, as well as to further acquisition of additional DNA. Here, we review a subgroup of GIs from E. coli termed pathogenicity islands (PAIs), a concept defined in the late 1980s by Jörg Hacker and colleagues in Werner Goebel's group at the University of Würzburg, Würzburg, Germany. As with other GIs, the PAIs comprise large genomic regions that differ from the rest of the genome by their G + C content, by their typical insertion within transfer RNA genes, and by their harboring of direct repeats (at their ends), integrase determinants, or other mobility loci. The hallmark of PAIs is their contribution to the emergence of virulent bacteria and to the development of intestinal and extraintestinal diseases. This review summarizes the current knowledge on the structure and functional features of PAIs, on PAI-encoded E. coli pathogenicity factors and on the role of PAIs in host-pathogen interactions.

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“…This pathogenesis is facilitated by colonization of the colon using a type 3 secretion system (T3SS) encoded on a pathogenicity island known as the locus of enterocyte effacement (LEE) (7). This cellular attachment mechanism is independent of any specific tissue-receptor tropism and is instead governed by numerous transcriptional regulators in the cell, which converge on the LEE to control its expression in response to niche-specific signals such as nutrients, pH, and quorum-sensing molecules (8–10). Furthermore, this T3SS delivers non–LEE-encoded effector (NLE) proteins into host cells, which are encoded on cryptic prophages scattered throughout the genome, which must also be integrated into the global regulatory circuit of the cell (11).…”

mentioning

confidence: 99%

Distinct intraspecies virulence mechanisms regulated by a conserved transcription factor

Connolly

O’Boyle

Turner

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Tailoring transcriptional regulation to coordinate the expression of virulence factors in tandem with the core genome is a hallmark of bacterial pathogen evolution. Bacteria encode hundreds of transcription factors forming the base-level control of gene regulation. Moreover, highly homologous regulators are assumed to control conserved genes between members within a species that harbor the same genetic targets. We have explored this concept in 2 Escherichia coli pathotypes that employ distinct virulence mechanisms that facilitate specification of a different niche within the host. Strikingly, we found that the transcription factor YhaJ actively regulated unique gene sets between intestinal enterohemorrhagic E. coli (EHEC) and extraintestinal uropathogenic E. coli (UPEC), despite being very highly conserved. In EHEC, YhaJ directly activates expression of type 3 secretion system components and effectors. Alternatively, YhaJ enhances UPEC virulence regulation by binding directly to the phase-variable type 1 fimbria promoter, driving its expression. Additionally, YhaJ was found to override the universal GAD acid tolerance system but exclusively in EHEC, thereby indirectly enhancing type 3 secretion pleiotropically. These results have revealed that within a species, conserved regulators are actively repurposed in a “personalized” manner to benefit particular lifestyles and drive virulence via multiple distinct mechanisms.

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Control freaks—signals and cues governing the regulation of virulence in attaching and effacing pathogens

Cited by 24 publications

References 94 publications

l -Arginine sensing regulates virulence gene expression and disease progression in enteric pathogens

l -Arginine sensing regulates virulence gene expression and disease progression in enteric pathogens

Pathogenicity Factors of Genomic Islands in Intestinal and Extraintestinal Escherichia coli

Distinct intraspecies virulence mechanisms regulated by a conserved transcription factor

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