The locus of enterocyte effacement-encoded regulator (Ler) is a regulatory

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that controls

bacterial Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

pathogenicity of enteropathogenic ''Escherichia coli'' (EPEC) and enterohemorrhagic ''Escherichia coli'' (EHEC). More specifically, Ler regulates the

locus of enterocyte effacement The locus of enterocyte effacement (LEE) is a moderately conserved pathogenicity island consisting of 35,000 base pairs in the bacteria ''Escherichia coli'' genome. The LEE encodes the Type III secretion system and associated chaperones and effe ...

(LEE)

pathogenicity island Pathogenicity islands (PAIs), as termed in 1990, are a distinct class of genomic islands acquired by microorganisms through horizontal gene transfer. Pathogenicity islands are found in both animal and plant pathogens. Additionally, PAIs are found i ...

genes, which are responsible for creating

intestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...

attachment and effacing lesions and subsequent

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

: LEE1, LEE2, and LEE3. LEE1, 2, and 3 carry the information necessary for a type III secretion system. The transcript encoding the Ler protein is the open reading frame 1 on the LEE1 operon. The mechanism of Ler regulation involves competition with histone-like nucleoid structuring protein (H-NS), a negative regulator of the LEE pathogenicity island. Ler is regulated by many factors such as plasmid encoded regulator (Per), integration host factor, Fis, BipA, a positive regulatory loop involving GrlA, and quorum sensing mediated by ''luxS''. __TOC__

Mechanism

Ler positively regulates the LEE genes by competition with its homolog, H-NS. H-NS silences LEE genes via rigid filament structures bound to the DNA that Ler disrupts and replaces through unknown mechanisms. 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''.

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. Integration host factor is also a direct activator of ''ler'' and binds upstream of its promoter. Jeannette Barba and her colleagues at the

National Autonomous University of Mexico The National Autonomous University of Mexico ( es, Universidad Nacional Autónoma de México, UNAM) is a public research university in Mexico. It is consistently ranked as one of the best universities in Latin America, where it's also the bigges ...

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''. Quorum sensing plays a role in Ler regulation. LuxS is an important protein involved in quorum sensing, particularly in the synthesis of

autoinducer Autoinducers are signaling molecules that are produced in response to changes in cell-population density. As the density of quorum sensing bacterial cells increases so does the concentration of the autoinducer. Detection of signal molecules by ba ...

molecules. Quorum-sensing ''E. coli'' regulator A (QseA) is found in LuxS systems and activates transcription of ''ler''. Fis, a nucleoid associated protein essential for EPEC's ability to form attaching and effacing lesions, partly acts through activation of Ler expression. BipA, a ribosomal binding GTPase and prolific regulator of EPEC virulence, transcriptionally regulates Ler from an upstream position where it also regulates other genes. The Ler protein also represses its own transcript on the LEE1 operon through DNA looping which prevents RNA polymerase from completing transcription.

References

{{Reflist Locus Gene expression