# Identification of Potential Therapeutic Targets Against Anthrax-Toxin-Induced Liver and Heart Damage

## TL;DR

This study identifies genes and proteins that could serve as new treatments for anthrax toxin-induced damage in the liver and heart.

## Contribution

The study identifies novel therapeutic targets, including PAI-1 and specific genes, for anthrax toxin-induced organ damage.

## Key findings

- Anthrax edema toxin (EdTx) and lethal toxin (LeTx) cause liver and heart damage in mice.
- Knockdown of Rgs1, Hcar2, Fosl2, Cxcl2, and Cxcl3 protects hepatocytes from EdTx-induced toxicity.
- PAI-1 (Serpine1) is crucial for LeTx-induced toxicity and its knockout increases LeTx tolerance.

## Abstract

Anthrax represents a disease resulting from infection by toxin-secreting bacteria, Bacillus anthracis. This research aimed to identify new therapeutic targets to combat anthrax. We performed assays to assess cell viability, apoptosis, glycogen consumption, and compound uptake and release in hepatocytes and cardiomyocytes responding to anthrax toxins. Microarray analysis was carried out to identify the genes potentially involved in toxin-induced toxicity. Knockdown experiments were performed to validate the contributions of the identified genes. Our study showed that anthrax edema toxin (EdTx) and lethal toxin (LeTx) induced lethal damage in mouse liver and heart, respectively. Microarray assays showed that 218 genes were potentially involved in EdTx-mediated toxicity, and 18 genes were potentially associated with LeTx-mediated toxicity. Among these genes, the knockdown of Rgs1, Hcar2, Fosl2, Hcar2, Cxcl2, and Cxcl3 protected primary hepatocytes from EdTx-induced cytotoxicity. Plasminogen activator inhibitor 1 (PAI-1)-encoding Serpine1 constituted the most significantly upregulated gene in response to LeTx treatment in mouse liver. PAI-1 knockout mouse models had a higher tolerance to LeTx compared with wild-type counterparts, suggesting that PAI-1 is essential for LeTx-induced toxicity and might represent a therapeutic target in LeTx-induced tissue damage. These results provide potential therapeutic targets for combating anthrax-toxin-induced liver and heart damage.