Pore-forming toxins in infection and immunity

Abstract

The integrity of the plasma membranes is extremely crucial for the survival and proper functioning of the cells. Organisms from all kingdoms of life employ specialized pore-forming proteins and toxins (PFPs and PFTs) that perforate cell membranes, and cause detrimental effects. PFPs/PFTs exert their damaging actions by forming oligomeric pores in the membrane lipid bilayer. PFPs/PFTs play important roles in diverse biological processes. Many pathogenic bacteria secrete PFTs for executing their virulence mechanisms. The immune system of the higher vertebrates employs PFPs to kill pathogen-infected cells and transformed cancer cells. The most obvious consequence of membrane pore-formation by the PFPs/PFTs is the killing of the target cells due to the disruption of the permeability barrier function of the plasma membranes. PFPs/PFTs can also activate diverse cellular processes that include activation of the stress-response pathways, induction of programmed cell death, and inflammation. Upon attack by the PFTs, host cells may also activate pathways to repair the injured membranes, restore cellular homeostasis, and trigger inflammatory immune responses. In this article, we present an overview of the diverse cellular responses that are triggered by the PFPs/PFTs, and their implications in the process of pathogen infection and immunity.

Current Perspective on the Membrane-Damaging Action of Thermostable Direct Hemolysin, an Atypical Bacterial Pore-forming Toxin

“…Pore-forming toxins (PFTs) are the unique class of proteins that damage cell membranes by forming pores in the membrane lipid bilayer (Mondal et al, 2018). Pore-formation in the cell membranes allows unregulated flow of ions, water, and other molecules that, in turn, perturb the cellular homeostasis and ultimately lead to cell death Verma et al, 2021). Molecular architectures of the PFTs are designed in such a specialised manner that allow them to be compatible with two distinct physicochemical environments.…”

“…PFTs are ubiquitously found in all the kingdoms of life. Notably, bacterial PFTs constitute the largest class of bacterial protein toxins, and play significant roles in their virulence mechanisms (Verma et al, 2021). Thermostable direct hemolysin (TDH) is one such PFT secreted by the Gram-negative bacterial pathogen Vibrio parahaemolyticus that is recognised as one of the major causative agents of the seafood-borne acute gastroenteritis (Wang et al, 2015;Cai and Zhang, 2018).…”

The Curious Case of Earthworms and COVID-19

“…Obviously, similar considerations and investigations should be given to the two other earthworm PFPs, fetidin and eiseniapore, perhaps as a combined approach. To support the approach, it is well-known that pore-forming proteins have important biological functions and that these can be therapeutically effective, e.g., against cancer, inflammatory diseases, and immunomodulation [68,[73][74][75]. Given this, it seems prudent to take an extra look at this humble earthworm to help us develop new treatments, also in the light of the mutation in the spike protein.…”

Protein-lipid interaction at low pH induces oligomerisation of the MakA cytotoxin from Vibrio cholerae

“…Aftab Nadeem 1,2,3 *, Alexandra Berg 1,3,4 , Hudson Pace 2,5,7 , Athar Alam 2,3,5 , Eric Toh 1,2,3 , Jörgen Ådén 2,6 , Nikola Zlatkov 1,2,3 , Si Lhyam Myint 1,2,3 , Karina Persson 2,6 , Gerhard Gröbner 2,6 , Anders Sjöstedt 2,3,5 , Marta Bally 2,5,7 , Jonas Barandun 1,3,4 Nuclei were counterstained with Hoechst 33342. Scale bars, 10 μm.…”

“…Both extracellular and intracellular bacterial pathogens produce and secrete host membrane-attacking pore-forming toxins (PFTs) to counteract host defenses, to promote colonization and spread, and to kill other bacteria 3,4 . PFTs can be categorized into two main groups, α-PFTs and β-PFTs, based on whether the secondary structure of the membrane-penetrating domain contains α-helices or β-barrels, respectively 3 .…”