Target intelligence / Profile preview

Bacillus anthracis lethal factor (LF)

Target
LF
Molecular classification
Enzyme, Zinc-dependent metalloprotease, Bacterial toxin component
01

Overview

Bacillus anthracis lethal factor (LF) is one of three components of the anthrax toxin secreted by Bacillus anthracis—the bacterium responsible for anthrax[1][3][6]. LF is an 85-kDa zinc-dependent metalloprotease enzyme that enters host cells via complex formation with another toxin component, protective antigen (PA)[1][2][3]. Once inside, LF specifically cleaves the N-terminus of mitogen-activated protein kinase kinases (MAPKKs), thereby inhibiting critical intracellular signaling pathways. This disruption leads to lethal cellular effects, particularly rapid death of macrophages through lysis or apoptosis, and ultimately contributes to multisystem organ failure in anthrax infection[1][2][4]. LF is a validated therapeutic target for toxin-neutralizing strategies, including small-molecule inhibitors or monoclonal antibodies (none currently approved for direct human therapy)[4][6].

Other names
LFanthrax lethal factorlethal toxin factor
02

Mechanism of action

Zinc metalloprotease activity: LF enters host cells with the help of protective antigen, then cleaves MAPKKs inside the cytoplasm, disrupting the MAPK signaling pathway and leading to immune cell apoptosis or lysis[1][3][4].

03

Biological functions

Cleavage of mitogen-activated protein kinase kinases (MAPKKs)Disruption of cellular signaling pathwaysInduction of cell death (notably in macrophages)Contribution to host immune evasion
04

Disease associations

Infection (specifically anthrax)Sepsis and immune system dysregulation (as a consequence of infection)
05

Safety considerations

Rapid and severe cytotoxicity (notable for fast deterioration in anthrax)Irreversible cellular damage if not neutralized early in infectionLack of clinically approved direct LF inhibitors; adjunctive agents are experimental
06

Interacting drugs

Small molecule hydroxamate inhibitors (experimental)

1 more in the full profile.

07

Biomarkers

Circulating anthrax lethal factor protein levels (for anthrax diagnosis and severity monitoring)PA and LF serum concentrations in clinical context

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