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

Pratima Verma,Kausik Chattopadhyay

doi:10.3389/fmolb.2021.717147

Abstract

Thermostable direct hemolysin (TDH) is the major virulence determinant of the gastroenteric bacterial pathogen Vibrio parahaemolyticus. TDH is a membrane-damaging pore-forming toxin (PFT). TDH shares remarkable structural similarity with the actinoporin family of eukaryotic PFTs produced by the sea anemones. Unlike most of the PFTs, it exists as tetramer in solution, and such assembly state is crucial for its functionality. Although the structure of the tetrameric assembly of TDH in solution is known, membrane pore structure is not available yet. Also, the specific membrane-interaction mechanisms of TDH, and the exact role of any receptor(s) in such process, still remain unclear. In this mini review, we discuss some of the unique structural and physicochemical properties of TDH, and their implications for the membrane-damaging action of the toxin. We also present our current understanding regarding the membrane pore-formation mechanism of this atypical bacterial PFT.

Highlights

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)
Being a potent PFT, Thermostable direct hemolysin (TDH) causes membrane damage that in turn can lead to the ion imbalance in the target cells
Available crystal structure has provided valuable insights regarding its structure-function relationship. It has revealed the unique structural fold adopted by TDH that has a striking resemblance to those of the actinoporin family of eukaryotic PFTs

Summary

Pratima Verma and Kausik Chattopadhyay *

Current Perspective on the Membrane-Damaging Action of Thermostable Direct Hemolysin, an Atypical Bacterial Pore-forming Toxin. TDH is a membranedamaging pore-forming toxin (PFT). The structure of the tetrameric assembly of TDH in solution is known, membrane pore structure is not available yet. The specific membrane-interaction mechanisms of TDH, and the exact role of any receptor(s) in such process, still remain unclear. In this mini review, we discuss some of the unique structural and physicochemical properties of TDH, and their implications for the membrane-damaging action of the toxin. We present our current understanding regarding the membrane pore-formation mechanism of this atypical bacterial PFT

INTRODUCTION

SECRETION AND REGULATION OF TDH

STRUCTURE AND PHYSICOCHEMICAL PROPERTIES OF TDH

PATHOPHYSIOLOGICAL FUNCTIONALITIES OF TDH

CONCLUSION