Posttranscriptional gene regulation in enterohemorrhagic Escherichia coli O157:H7 246 views

Bacteria must sense and respond to environmental cues to survive and replicate in diverse environments. Tight regulation of metabolic and virulence gene expression is required for pathogens to compete with the host microbiota, replicate, and subvert the immune system. The foodborne pathogen enterohemorrhagic Escherichia coli O157:H7 (EHEC) has a very low infectious dose, indicating successful adaptation to the various environments in the gastrointestinal (GI) tract. Whereas the role of transcriptional regulators in EHEC niche adaptation has been thoroughly elucidated, less is known about the contributions of posttranscriptional regulators. Furthermore, most posttranscriptional regulatory networks were characterized in the lab-adapted Escherichia coli K12 strain. However, EHEC encodes an additional 1.34 Mb of DNA compared to E. coli K12. Recent work has identified EHEC-specific regulatory factors; however, the contribution of the pathogen-specific factors to regulation of core-encoded and pathogenicity island-encoded genes remains unknown. Our goal was to provide the initial characterization of the pathogen-specific sRNA MavR. Furthermore, we describe a unique mechanism of sRNA-dependent regulation in which a sRNA binds to the coding region of an mRNA to prevent cleavage by RNase E thereby stabilizing the transcript. Furthermore, we identify a role for MavR in regulation of metabolism, motility, stress responses, type III secretion, and fitness in the gastrointestinal tract. Importantly, we provide evidence that a pathogen-specific sRNA regulates expression of core-encoded and non-core-encoded genes emphasizing the importance of studying posttranscriptional gene regulation in relevant pathogens.

PHD (Doctor of Philosophy)

EHEC; sRNA; posttranscriptional; gene regulation; enterohemorrhagic Escherichia coli

English

2021-06-07