Cellular Microbiology of Bacterial Toxins
Deadline for manuscript submissions: closed (15 January 2011) | Viewed by 88572
Interests: microbial toxins in host pathogen interactions; host epithelium and endothelium barriers; inflammation; cell cytoskeleton; toxin and bacterial entry; cell signaling : Rho GTPases; regulation by ubiquitination; MAP Kinases
Protein toxins secreted by pathogenic bacteria such as Anthrax, Tetanus and Diphtheria toxins are among the most potent poisons, but also valuable targets for developing efficient vaccines. These “molecular syringe” devices are composed of three functional parts sequentially involved in the three steps of the intoxication process: (1) plasma membrane interaction and endocytosis, (2) translocation through host cell membrane compartments and (3) targeting of key cellular signaling pathways. Another family of protein toxins acts directly on host cell plasma membrane by forming pores for corrupting specific signaling pathways.
This special issue on the Cellular Biology of Bacterial Toxins covers recent exciting findings on various aspects of the mode of action of several harmful toxins in relationship to key host cellular functions. Other complementary aspects have been covered in a recent special issue edited by Dr Yasuhiko Horiguchi.
(1) The first step of intoxication consists in the interaction of toxins with the plasma membrane of host cells. (i) Upon interaction, pore forming toxins directly interfere on intracellular signaling for instance via release of intracellular potassium. (ii) Other toxins, upon association with specific host cell surface receptors, are routed into various host cell compartments. Recent findings have elucidated new aspects on the entry and complex retrograde traffic of Shiga toxin and the closely related plant toxin Ricin.
(2) Upon reaching specific intracellular compartments, the translocation-domain of the toxins inserts into the lipid bilayer and drives the transport of the catalytic subunit into the cytosol. Major progress has been made in deciphering the structure of the pore of anthrax toxin and the translocation of the enzymatic components of this toxin through the pore. Evidences also suggest a hijacking of cellular components by diphtheria toxin to efficiently cross endosomal membranes.
(3) Once inside the cytosol the catalytic part of toxins directly corrupts the regulation of master regulators of host cells homeostasis. Deciphering the molecular mechanism of action of toxins thus informed us on the function and regulation of key cellular proteins. Recent findings have unveiled that some bacterial factors modify Rho GTPases by Adenylylation (AMPylation) and can interfere with cell signaling by ubiquitin and ubiquitin-like molecules. This also contributes to define the function of toxin targets in cell biology such as the crosstalk between regulations of actin and microtubule cytoskeleton.
Dr. Emmanuel Lemichez
- protein toxins
- pathogenic bacteria
- endocytosis and vesicle trafficking
- cell cycle
- actin cytoskeleton
- microtubule cytoskeleton
- Rho GTPases