EspJ Is a Prophage-Carried Type III Effector Protein of Attaching and Effacing Pathogens That Modulates Infection Dynamics

Dahan, Sivan; Wiles, Siouxsie; Ragione, Roberto M. La; Best, Angus; Woodward, Martin J.; Stevens, Mark P.; Shaw, Robert K.; Chong, Y. F.; Knutton, Stuart; Phillips, Alan D.; Frankel, Gad

doi:10.1128/iai.73.2.679-686.2005

Cited by 73 publications

(61 citation statements)

References 49 publications

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“…1A). This locus spans 12.6 kb and also contains the gene coding for the T3SS-translocated effector EspJ, which is found in a different location in EHEC and EPEC (11). Besides the described effector genes, in this locus we found an open reading frame of 293 codons immediately upstream of nleF, whose product shares 15% FIG.…”

Section: Resultsmentioning

confidence: 96%

Regulation of Expression and Secretion of NleH, a New Non-Locus of Enterocyte Effacement-Encoded Effector in Citrobacter rodentium

et al. 2008

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Together with enterohemorrhagic Escherichia coli and enteropathogenic Escherichia coli, Citrobacter rodentium is a member of the attaching-and-effacing (A/E) family of bacterial pathogens. A/E pathogens use a type III secretion system (T3SS) to translocate an assortment of effector proteins, encoded both within and outside the locus of enterocyte effacement (LEE), into the colonized host cell, leading to the formation of A/E lesions and disease. Here we report the identification and characterization of a new non-LEE encoded effector, NleH, in C. rodentium. NleH is conserved among A/E pathogens and shares identity with OspG, a type III secreted effector protein in Shigella flexneri. Downstream of nleH, genes encoding homologues of the non-LEE-encoded effectors EspJ and NleG/NleI are found. NleH secretion and translocation into Caco-2 cells requires a functional T3SS and signals located at its amino-terminal domain. Transcription of nleH is not significantly reduced in mutants lacking the LEE-encoded regulators Ler and GrlA; however, NleH protein levels are highly reduced in these strains, as well as in escN and cesT mutants. Inactivation of Lon, but not of ClpP, protease restores NleH levels even in the absence of CesT. Our results indicate that the efficient engagement of NleH in active secretion is needed for its stability, thus establishing a posttranslational regulatory mechanism that coregulates NleH levels with the expression of LEE-encoded proteins. A C. rodentium nleH mutant shows a moderate defect during the colonization of C57BL/6 mice at early stages of infection.

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Section: Resultsmentioning

confidence: 96%

Regulation of Expression and Secretion of NleH, a New Non-Locus of Enterocyte Effacement-Encoded Effector in Citrobacter rodentium

et al. 2008

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“…The espJ-tccP operon , for instance, was downregulated in TW14359 (,1.5-fold), an unexpected result given that TccP plays a critical role in EHEC pedestal formation . However, espJ is not required for pedestal formation, and the deletion of espJ in Citrobacter rodentium and O157 : H7 resulted in more persistent colonization of mice and lamb, respectively (Dahan et al, 2005). Indeed, the expression of the espJ-tccP operon is influenced by multiple environmental signals, and its regulation is unknown .…”

Section: Discussionmentioning

confidence: 99%

Differences in adherence and virulence gene expression between two outbreak strains of enterohaemorrhagic Escherichia coli O157 : H7

et al. 2010

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The Escherichia coli O157 : H7 TW14359 strain was implicated in a multi-state outbreak in North America in 2006, which resulted in high rates of severe disease. Similarly, the O157 : H7 RIMD0509952 (Sakai) strain caused the largest O157 : H7 outbreak to date. Both strains were shown to represent divergent phylogenetic lineages. Here we compared global gene expression patterns before and after epithelial cell exposure, as well as the ability to adhere to and invade epithelial cells, between the two outbreak strains. Epithelial cell assays demonstrated a 2.5-fold greater adherence of the TW14359 strain relative to Sakai, while whole-genome microarrays detected significant differential expression of 914 genes, 206 of which had a fold change ≥1.5. Interestingly, most locus of enterocyte effacement (LEE) genes were upregulated in TW14359, whereas flagellar and chemotaxis genes were primarily upregulated in Sakai, suggesting discordant expression of these genes between the two strains. The Shiga toxin 2 genes were also upregulated in the TW14359 strain, as were several pO157-encoded genes that promote adherence, including type II secretion genes and their effectors stcE and adfO. Quantitative RT-PCR confirmed the expression differences detected in the microarray analysis, and expression levels were lower for a subset of LEE genes before versus after exposure to epithelial cells. In all, this study demonstrated the upregulation of major and ancillary virulence genes in TW14359 and of flagellar and chemotaxis genes in Sakai, under conditions that precede intimate bacterial attachment to epithelial cells. Differences in the level of adherence to epithelial cells were also observed, implying that these two phylogenetically divergent O157 : H7 outbreak strains vary in their ability to colonize, or initiate the disease process.

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“…tccP is carried on prophage CP-933U, forming an operon with the upstream gene espJ (10), which encodes another effector protein. EspJ was shown to influence the dynamics of clearance of the pathogen from the host's intestinal tract, suggesting a role in host survival and pathogen transmission in vivo; EspJ is not required for A/E lesion formation in cultured cells and ex vivo (5). Significantly, while espJ has been found in all the genomes of the sequenced A/E lesionforming bacteria, tccP was exclusively found in the genomes of two sequenced EHEC O157:H7 isolates, EDL933 (25) and Sakai (17) strains.…”

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Distribution of tccP in Clinical Enterohemorrhagic and Enteropathogenic Escherichia coli Isolates

et al. 2005

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Enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) are diarrheagenic pathogens that colonize the gut through the formation of attaching and effacing lesions, which depend on the translocation of effector proteins via a locus of enterocyte effacement-encoded type III secretion system. Recently, two effector proteins, EspJ and TccP, which are encoded by adjacent genes on prophage CP-933U in EHEC O157:H7, have been identified. TccP consists of a unique N-terminus region and several proline-rich domains. In this project we determined the distribution of tccP in O157:H7, in non-O157 EHEC, and in typical and atypical EPEC isolates. All the EHEC O157:H7 strains tested were tccP ؉ . Unexpectedly, tccP was also found in non-O157 EHEC, and in typical and atypical EPEC isolates, particularly in strains belonging to serogroups O26 (EHEC), O119 (typical EPEC), and O55 (atypical EPEC). We recorded some variation in the length of tccP, which reflects diversity in the number of the proline-rich repeats. These results show the existence of a class of "attaching and effacing" pathogens which express a combination of EPEC and EHEC virulence determinants.

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EspJ Is a Prophage-Carried Type III Effector Protein of Attaching and Effacing Pathogens That Modulates Infection Dynamics

Cited by 73 publications

References 49 publications

Regulation of Expression and Secretion of NleH, a New Non-Locus of Enterocyte Effacement-Encoded Effector in Citrobacter rodentium

Regulation of Expression and Secretion of NleH, a New Non-Locus of Enterocyte Effacement-Encoded Effector in Citrobacter rodentium

Differences in adherence and virulence gene expression between two outbreak strains of enterohaemorrhagic Escherichia coli O157 : H7

Distribution of tccP in Clinical Enterohemorrhagic and Enteropathogenic Escherichia coli Isolates

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