Disease relevance of lef

• We studied the effects on Bacillus anthracis growth and the virulence gene (pagA, lef, and cya) expression of the QS inhibitor (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone, which is naturally synthesized by the marine alga Delisea pulchra, as well as a related compound and synthetic derivatives [1].
• Through quantitative reverse transcription-PCR assays, this toxin-inhibitory effect was shown to occur at the transcriptional level, since amounts of mRNA for pagA (PA), lef (LF), and cya (edema factor) were reduced [2].
• Bacillus anthracis plasmid pXO1 carries the structural genes for the three anthrax toxin proteins, cya (edema factor), lef (lethal factor), and pag (protective antigen) [3].

High impact information on lef

• Lethal factor (LF) is a protein (relative molecular mass 90,000) that is critical in the pathogenesis of anthrax [4].
• Lethal factor is a protease, one component of Bacillus anthracis exotoxin, which cleaves many of the mitogen-activated protein kinase kinases (MEKs) [5].
• When furanones were added to midlog-phase cultures of B. anthracis strains with LacZ reporters in pagA, lef, or cya, growth was inhibited, and expression of these virulence genes was inhibited to a proportionately greater extent [1].
• Lethal factor and edema factor, individually or in combination, are incapable of lysing red blood cells [6].
• Lethal factor active-site mutations affect catalytic activity in vitro [7].

Chemical compound and disease context of lef

• The Bacillus anthracis toxin genes, cya, lef, and pag, can be viewed as a regulon, in which transcription of all three genes is activated in trans by the same regulatory gene, atxA, in response to the same signal, CO2 [8].

Biological context of lef

• This region contains the three toxin genes (cya, lef, and pagA), regulatory elements controlling the toxin genes, three germination response genes, and 19 additional ORFs [9].
• Nucleotide sequence and analysis of the lethal factor gene (lef) from Bacillus anthracis [10].
• Whereas pXO2 harbours the cap operon coding for the capsule, pXO1 contains the pag, lef, and cya genes coding for protective antigen, lethal, and oedema factors, respectively, as well as the atxA regulatory gene [11].
• Lethal factor contains the highly conserved zinc-binding consensus sequence, HExxH, that is present in all known zinc metalloproteases [12].

Anatomical context of lef

• Lethal factor of Bacillus anthracis cleaves the N-terminus of MAPKKs: analysis of the intracellular consequences in macrophages [13].

Associations of lef with chemical compounds

• A kanamycin resistance cassette was inserted in each cya (encoding EF) and lef (encoding LF) gene, and the constructs were separately introduced into B. anthracis Sterne on a mobilizable shuttle plasmid [14].
• Lethal factor treated with EDTA and o-phenanthroline contained a similar number of zinc atoms, indicating that all three zinc atoms are tightly bound to the protein [12].

Other interactions of lef

• A dual-color PCR was set up with primers and probes for the chromosomal marker rpoB and the plasmid marker lef [15].

References