الفهرس 
Introduction
Chapter 1Only 14 pages are availabe for public view
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Abstract
EAEC is implicated as a major agent mediating pediatric diarrhea, suggesting that it is an important pathogen. The master transcription regulator, AggR, acts to positively regulate virulence gene expression in most EAEC strains, and AggR has been reported to be negatively regulated by Aar (27, 173).Hence, EAEC is increasingly recognized as an emerging enteric pathogen with high level of antibiotic resistance in Egypt. Studying the action of the key regulator and engineering AaR to reduce expression of these virulence determinants may offer promising approaches to defeat EAEC infections and to tackle the global challenge of antimicrobial resistance Here, we identified Egyptian typicalEAEC strains and atypical EAEC strains trying to find their virulence profile by doing Next-generation complete genome sequencing. In addition, we investigate the AggR regulon in different EAEC strains. Moreover, we examine the regulation of AaR by identifying the promoter element and knocking the AggR-binding sites and -10 element required for its regulation and activation by doing mutational analysis. Finally, we examined the inhibitory effect of AaR on different AggR regulated promoters using galactosidase assays and biofilm formation.
We suppose that AggR activation does not need any chemical inducer, and induction in EAEC appears to be stochastic. Moreover, this result argues Yasir et al. (2018)(24) findings in explaining and finding the exact way of AggR regulation, especially with AggR-dependent activation in laboratory E. coli K-12 strain, without any special induction conditions. Finally, we assume that this random way of AggR activation and regulation may be the cause that some EAEC strains like E43 and E44 do not have AggR , and why some strains are pathogenic causing disease and the other not. Moreover, this study highlighted the potential importance of strain differences in determining pathogenicity. Finally, we supposed that AaR acts on the basal level of AggR activation, and the differences in basal AggR-independent activities of the aggR promoter affects the frequency of AaR repressive effect. So, AaR plays as a bi-stable switch activated by AggR, and overexpression of AggR will lead to expression of AaR, evolving strain to strain to dampen down expression of virulence determinants and encourage the idea that working on E36-AaR and finding new more effective versions of AaR will help us to make EAEC harmless.
This study aimed to evaluate the contribution of AggR and Aar to the regulation of virulence gene expression. Understanding more about these proteins and their role(s) may facilitate the development of virulence attenuation strategies.As, EAEC is increasingly recognized as an emerging enteric pathogen with high level of antibiotic resistance in Egypt. Studying the action of the key regulator and engineering AaR to reduce expression of these virulence determinants may offer promising approaches to defeat EAEC infections and to tackle the global challenge of antimicrobial resistance