Bacterial Toxins
Bacterial protein toxins are released by pathogens into the environment. Thereafter, the toxins target eukaryotic cells in order to damage the membrane, to induce pathogenic signaling by acting on membrane receptors or to disturb cell signaling and cell f
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Bacterial Toxins Gudula Schmidt and Klaus Aktories Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, AlbertLudwigs-Universität Freiburg, Freiburg, Germany
Uptake Protein toxins acting intracellularly are often composed of two subunits (A/B model). One subunit is catalytic (A-subunit) and the other is responsible for binding and cell entry (B-subunit). Following binding to an extracellular membrane receptor, the toxins are endocytosed. From the endosomes, the A-subunit is directly (pH dependent) transferred into the cytosol (e.g., diphtheria toxin and anthrax toxin) or the toxin is transported in a retrograde manner via the Golgi to the ER (e. g., cholera toxin), where translocation into the cytosol occurs (Schiavo and van der Goot 2001).
Mechanism of Action Toxins Modifying Target Proteins Protein toxins of this type are generally very potent and efficient, because they act catalytically on specific substrates. The toxins usually activate or inactivate key eukaryotic proteins involved in essential cellular functions by covalent
modification. One subfamily catalyzes the ADPribosylation of target proteins. For unknown reasons, many toxins of this subfamily modify eukaryotic GTPases. Examples are the diphtheria toxin from toxigenic Corynebacterium diphtheriae and the Pseudomonas aeruginosa exotoxin A, which ADP-ribosylate elongation factor 2 at diphthamide to cause inhibition of protein synthesis (Table 1). Pertussis toxin from Bordetella pertussis and cholera toxin from Vibrio cholerae act on heterotrimeric G proteins. Pertussis toxin consists of the catalytic subunit S1 and five binding subunits (S2, S3, 2 S4, and S5) with masses of 11–26 kDa. Cholera toxin consists of a 28 kDa A-subunit and five B-subunits (12 kDa). Although pertussis toxin ADP-ribosylates the α-subunits of the Gi subfamily of G proteins (exception Gz) at a cysteine residue, cholera toxin and the related E. coli heat labile toxins ADP-ribosylate α-subunits of the Gs subfamily at an arginine residue. Pertussis toxin– induced ADP-ribosylation blocks the interaction of the G protein with heptahelical receptors (GPCR). The ADP-ribosylation of Gs inhibits intrinsic GTPase activity and persistently activates the G protein. Increase in cellular cAMP, activation of protein kinase A, and subsequent disturbance of cellular electrolyte secretion is suggested to be the cause of cholera toxin– induced diarrhea. A recently characterized class of toxins (toxin complexes, TC) is produced by the entomopathogenic bacterium Photorhabdusluminescens. It resembles a
© Springer-Verlag Berlin Heidelberg New York 2020 S. Offermanns, W. Rosenthal (eds.), Encyclopedia of Molecular Pharmacology, https://doi.org/10.1007/978-3-030-21573-6_26-1
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Bacterial Toxins
Bacterial Toxins, Table 1 Intracellularly acting exotoxins Toxin Diphtheria toxin, Pseudomonas exotoxin A Cholera toxin, heat labile E. coli toxins Pertussis toxin C. botulinum C2-toxin and related toxins C. botulinum C3-toxin and related toxins E. coli CNF1, 2 and 3, Yersinia CNFy Bordete
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