The Type Three Secretion System 2-Encoded Regulator EtrB Modulates Enterohemorrhagic Escherichia coli Virulence Gene Expression

Abstract

bEnterohemorrhagic Escherichia coli O157:H7 (EHEC) is a foodborne pathogen that causes bloody diarrhea and hemolytic uremic syndrome throughout the world. A defining feature of EHEC pathogenesis is the formation of attaching and effacing (AE) lesions on colonic epithelial cells. Most of the genes that code for AE lesion formation, including a type three secretion system (T3SS) and effectors, are carried within a chromosomal pathogenicity island called the locus of enterocyte effacement (LEE). In this study, we report that a putative regulator, which is encoded in the cryptic E. coli type three secretion system 2 (ETT2) locus and herein renamed EtrB, plays an important role in EHEC pathogenesis. The etrB gene is expressed as a monocistronic transcript, and EtrB autoregulates expression. We provide evidence that EtrB directly interacts with the ler regulatory region to activate LEE expression and promote AE lesion formation. Additionally, we mapped the EtrB regulatory circuit in EHEC to determine a global role for EtrB. EtrB is regulated by the transcription factor QseA, suggesting that these proteins comprise a regulatory circuit important for EHEC colonization of the gastrointestinal tract.

Escherichia coli ST302: Genomic Analysis of Virulence Potential and Antimicrobial Resistance Mediated by Mobile Genetic Elements

“…ETT2 shares homology to the Salmonella type 3 secretion system located on the Salmonella pathogenicity island 1 (SPI-1). Though it is thought unlikely that ETT2 functions as a secretion system, it is known to influence virulence by regulating VAGs expression (Zhou et al, 2014;Luzader et al, 2016), promoting motility, adhesion, biofilm formation and serum survival (Zhou et al, 2014;Shulman et al, 2018), and enhancing invasion and intracellular survival (Yao et al, 2009). While most E. coli strains possess ETT2 gene clusters, the vast majority have undergone extensive deletions and mutations (Ren et al, 2004;Zhou et al, 2014).…”

Advances and Challenges in Studying Type III Secretion Effectors of Attaching and Effacing Pathogens

“…Moving forward, the employment of techniques that do not rely on homology offer less bias and are therefore preferable. Additionally, A/E pathogens that encode a second functional T3SS (named ETT2) may also secrete its own cognate effectors (Fox et al, 2020 ), and secretion substrates could be shared between the two T3SSs, as there is evidence for regulatory crossover (Zhang et al, 2004 ; Luzader et al, 2016 ).…”

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

“…Within EHEC, there is also a secondary non-functional E. coli type three secretion system 2 (ETT2), which has a putative regulator, EtrB [58]. EtrB has been shown to directly interact with ler to activate LEE expression and is positively regulated by QseA [58].…”

“…Within EHEC, there is also a secondary non-functional E. coli type three secretion system 2 (ETT2), which has a putative regulator, EtrB [58]. EtrB has been shown to directly interact with ler to activate LEE expression and is positively regulated by QseA [58]. ETT2 contains five predicted transcription factors including EtrA and EivF which have been shown to repress LEE expression [59].…”

“…ETT2 contains five predicted transcription factors including EtrA and EivF which have been shown to repress LEE expression [59]. EtrB modulates the expression of the T3SS by repressing expression of etrA and eivF and positively interacting directly with the LEE1 promoter region [58].…”