Vacuolating cytotoxin A (VacA) - A multi-talented pore-forming toxin from Helicobacter pylori.
Helicobacter pylori is associated with severe and chronic diseases of the stomach and duodenum such as peptic ulcer, non-cardial adenocarcinoma and gastric lymphoma, making Helicobacter pylori the only bacterial pathogen which is known to cause cancer. The worldwide rate of incidence for these diseases is extremely high and it is estimated that about half of the world's population is infected with H. pylori. Among the bacterial virulence factors is the vacuolating cytotoxin A (VacA), which represents an important determinant of pathogenicity. Intensive characterization of VacA over the past years has provided insight into an ample variety of mechanisms contributing to host-pathogen interactions. The toxin is considered as an important target for ongoing research for several reasons: i) VacA displays unique features and structural properties and its mechanism of action is unrelated to any other known bacterial toxin; ii) the toxin is involved in disease progress and colonization by H. pylori of the stomach; iii) VacA is a potential and promising candidate for the inclusion as antigen in a vaccine directed against H. pylori and iv) the vacA gene is characterized by a high allelic diversity, and allelic variants contribute differently to the pathogenicity of H. pylori. Despite the accumulation of substantial data related to VacA over the past years, several aspects of VacA-related activity have been characterized only to a limited extent. The biologically most significant effect of VacA activity on host cells is the formation of membrane pores and the induction of vacuole formation. This review discusses recent findings and advances on structure-function relations of the H. pylori VacA toxin, in particular with a view to membrane channel formation, oligomerization, receptor binding and apoptosis.
Department of Pharmacy, Division of Pharmacology, University of Malakand, Khyber Pakhtunkhwa 18550, Pakistan; Bacterial Toxin Research Cluster, Institute of Molecular Biosciences, Mahidol University, Nakornpathom 73170, Thailand. Electronic address: juniphdr@gmail.com.
Muhammad
M
Junaid
Bacterial Toxin Research Cluster, Institute of Molecular Biosciences, Mahidol University, Nakornpathom 73170, Thailand. Electronic address: aung.k.lynn@gmail.com.
Aung Khine
AK
Linn
Bacterial Toxin Research Cluster, Institute of Molecular Biosciences, Mahidol University, Nakornpathom 73170, Thailand. Electronic address: mohammad.jav@mahidol.ac.th.
Mohammad Bagher
MB
Javadi
Bacterial Toxin Research Cluster, Institute of Molecular Biosciences, Mahidol University, Nakornpathom 73170, Thailand. Electronic address: sarbastem@yahoo.com.
Sarbast
S
Al-Gubare
Department of Basic Medical Sciences, Khyber Medical University, Peshawar 25000, Pakistan. Electronic address: niazpharmacist@yahoo.com.
Niaz
N
Ali
Bacterial Toxin Research Cluster, Institute of Molecular Biosciences, Mahidol University, Nakornpathom 73170, Thailand. Electronic address: katzenmeier.ger@mahidol.ac.th.
Gerd
G
Katzenmeier
D000483:Alleles; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D002462:Cell Membrane / Q000187:drug effects*; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D049990:Membrane Transport Modulators / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D011110:Polymorphism, Genetic; D016062:Porosity / Q000187:drug effects; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals; D021381:Protein Transport; D059748:Proteolysis
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D049990:Membrane Transport Modulators; D010446:Peptide Fragments; D021382:Protein Sorting Signals; C074689:VacA protein, Helicobacter pylori
Helicobacter pylori; Pore-forming toxin; Structure; Vacuolating cytotoxin VacA; Virulence factor