Why should cell biologists study microbial pathogens?

Welch, Matthew D.

Studying pathogens has also led to fundamental advances in the field of membrane trafficking. A classic example involves the extracellular bacterial pathogens C. botulinum, mentioned above, as well as Clostridium tetani, which causes the paralytic disease tetanus. In addition to the C3 exoenzyme, C. botulinum produces botulinum toxins A-G (type A is familiarly known as Botox), and C. tetani secretes tetanus toxin. These toxins specifically cleave SNARE protein components of the vesicle fusion machinery, including VAMP, SNAP-25, and syntaxin (Link et al., 1992; Schiavo et al., 1992; Blasi et al., 1993a,b) . Microinjection of nerve cells with these toxins showed that SNARE molecules are critical for neurotransmitter release via vesicle fusion with the plasma membrane (Schiavo et al., 1992; Blasi et al., 1993b) . Preventing neurotransmitter release results in the paralysis caused by botulinum and tetanus toxins. In a contemporary study, it was revealed that SNARE proteins form a complex that is sufficient to mediate vesicle docking and fusion (Söllner et al., 1993) . Thus bacterial toxins were used in discovering fundamental mechanisms of membrane fusion and vesicular transport.