Ler positively regulates the LEE genes by competition with its homolog, H-NS.[5] H-NS silences LEE genes via rigid filament structures bound to the DNA that Ler disrupts and replaces through unknown mechanisms.[5][6] Though little is known of the mechanism of Ler regulation, Ler interacts with DNA in specific ways. Ler binds DNA non-cooperatively, bends DNA in low concentrations, stiffens it in high concentration, and forms toroidal nucleoprotein complexes along DNA in vivo.[5][7]
Regulation
The regulation of Ler and its transcript, ler, is complex and many-fold. The plasmid encoded regulator (per) directly activates the region of the LEE1 operon which encodes Ler.[1] Integration host factor is also a direct activator of ler and binds upstream of its promoter.[8]
Jeannette Barba and her colleagues at the National Autonomous University of Mexico elucidated a positive regulatory loop between Ler, ler, GrlA, and grlRA. GrlA is also a LEE encoded regulator of the LEE pathogenicity island. They found that GrlA activates ler, and that Ler activates grlRA indicating a loop of activation wherein a protein product activates a transcript whose protein product activates the transcript of the original protein. Ler activates grlRA only if H-NS is present, this is not the case for GrlA activation of ler.[4]
Quorum sensing plays a role in Ler regulation. LuxS is an important protein involved in quorum sensing, particularly in the synthesis of autoinducer molecules. Quorum-sensing E. coli regulator A (QseA) is found in LuxS systems and activates transcription of ler.[3] Fis, a nucleoid associated protein essential for EPEC's ability to form attaching and effacing lesions, partly acts through activation of Ler expression.[9] BipA, a ribosomal binding GTPase and prolific regulator of EPEC virulence, transcriptionally regulates Ler from an upstream position where it also regulates other genes.[10]
The Ler protein also represses its own transcript on the LEE1 operon through DNA looping which prevents RNA polymerase from completing transcription.[11][12]
References
^ abcdMellies, J. L.; Elliott, S. J.; Sperandio, V.; Donnenberg, M. S.; Kaper, J. B. (July 1999). "The Per regulon of enteropathogenic Escherichia coli : identification of a regulatory cascade and a novel transcriptional activator, the locus of enterocyte effacement (LEE)-encoded regulator (Ler)". Molecular Microbiology. 33 (2): 296–306. doi:10.1046/j.1365-2958.1999.01473.x. ISSN0950-382X. PMID10411746. S2CID23881901.
^Goldberg, M. D.; Johnson, M.; Hinton, J. C. D.; Williams, P. H. (2001-08-01). "Role of the nucleoid-associated protein Fis in the regulation of virulence properties of enteropathogenic Escherichia coli". Molecular Microbiology. 41 (3): 549–559. doi:10.1046/j.1365-2958.2001.02526.x. ISSN1365-2958. PMID11532124.
