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Review
. 2016 Sep 21:6:105.
doi: 10.3389/fcimb.2016.00105. eCollection 2016.

The Tip of the Iceberg: On the Roles of Regulatory Small RNAs in the Virulence of Enterohemorrhagic and Enteropathogenic Escherichia coli

Shantanu Bhatt  1 , Marisa Egan  1 , Valerie Jenkins  1 , Sarah Muche  1 , Jihad El-Fenej  1
Affiliations
Review

The Tip of the Iceberg: On the Roles of Regulatory Small RNAs in the Virulence of Enterohemorrhagic and Enteropathogenic Escherichia coli

Shantanu Bhatt et al. Front Cell Infect Microbiol. .

Abstract

Enterohemorrhagic and enteropathogenic Escherichia coli are gastrointestinal pathogens that disrupt the intestinal microvilli to form attaching and effacing (A/E) lesions on infected cells and cause diarrhea. This pathomorphological trait is encoded within the pathogenicity island locus of enterocyte effacement (LEE). The LEE houses a type 3 secretion system (T3SS), which upon assembly bridges the bacterial cytosol to that of the host and enables the bacterium to traffic dozens of effectors into the host where they hijack regulatory and signal transduction pathways and contribute to bacterial colonization and disease. Owing to the importance of the LEE to EHEC and EPEC pathogenesis, much of the research on these pathogens has centered on its regulation. To date, over 40 proteinaceous factors have been identified that control the LEE at various hierarchical levels of gene expression. In contrast, RNA-based regulatory mechanisms that converge on the LEE have only just begun to be unraveled. In this minireview, we highlight major breakthroughs in small RNAs (sRNAs)-dependent regulation of the LEE, with an emphasis on their mechanisms of action and/or LEE-encoded targets.

Keywords: EHEC; EPEC; LEE; posttranscriptional; sRNA; transcriptional.

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Figures

Figure 1
Figure 1
Hfq and sRNA-dependent regulation of the LEE in EHEC and EPEC. The locus of enterocyte effacement (LEE) pathogenicity island includes the multicistronic operons LEE1-5, the bicistronic operon grlRA, and multiple monocistronic transcription units. In an inducible environment the master regulator Ler orchestrates the synchronous transcriptional activation from the other LEE operons, including grlRA, which culminates with morphogenesis of A/E lesions. GrlA and GrlR participate in a complex positive and negative feedback loop with ler respectively to refine transcription from the LEE. In the EHEC strain EDL933 Hfq represses the LEE by destabilizing the grlRA mRNA as well as by targeting the 5′ UTR of ler. In EHEC 86-24 Hfq activates LEE via ler, and multiple trans-encoded sRNAs, integrated at different regulatory checkpoints, are involved in this regulation. These include sRNA350, sRNA103, sRNA56, GlmZ, and GlmY. In the EHEC strain Sakai the cis-encoded sRNA Arl silences LEE by repressing ler. In EPEC, Hfq represses the LEE by targeting grlRA. The figure has been modified from Bhatt et al. (2011).
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