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Environmental microbiology

Environmental microbiology

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Systemic mitochondrial disruption is a key event in the toxicity of bacterial pore-forming toxins to Caenorhabditis elegans

Published:1 September 2021 DOI: 10.1111/1462-2920.15376 PMID: 33368933
Jianwei Shi, Fengjuan Zhang, Ling Chen, Alejandra Bravo, Mario Soberón, Ming Sun

Abstract

Pore-forming toxins (PFTs) are important weapons of multiple bacterial pathogens to establish their infections. PFTs generally form pores in the plasma membrane of target cells; however, the intracellular pathogenic processes triggered after pore-formation remain poorly understood. Using Caenorhabditis elegans as a model and Bacillus thuringiensis nematicidal Cry PFTs, we show here that the localized PFT attack causes a systemic mitochondrial damage, important for the PFT toxicity. We find that PFTs punch pores only in gut cells of nematodes, but unexpectedly mitochondrial disruption is able to occur in distal unperforated regions, such as the head and muscle tissues. We demonstrate that PFTs affect the activity of the mitochondrial respiratory chain (MRC) complex I resulting in the loss of mitochondrial membrane potential (ΔΨm ), which causes further mitochondrial fragmentation and the reduction of total mitochondrial content. Worms with decreased ΔΨm or inhibited MRC activity show higher sensitivity to PFTs. The inhibition of mitochondrial fission or the increase of mitochondrial content markedly improves the survival of animals treated with PFTs. These findings suggest that mitochondrial changes underpin PFT-mediated toxicity against nematodes and that systemic mitochondrial disruption caused by localized pore-formation represents a conserved key intracellular event in the mode of action of PFTs.

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Materials
Procduct Name CAS Molecular Formula Supplier Price
FCCP 370-86-5 C10H5F3N4O 202 suppliers $9.00-$2240.00
FCCP 370-86-5 C10H5F3N4O 202 suppliers $9.00-$2240.00
FCCP 370-86-5 C10H5F3N4O 202 suppliers $9.00-$2240.00
FCCP 370-86-5 C10H5F3N4O 202 suppliers $9.00-$2240.00

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