Bacterial Moonlighting Proteins with Toxin-like Actions
Bacterial toxins have been feared since the early days of bacteriology. The toxin concept rose from the study of diphtheria, a disease localized in the throat, but with systemic manifestation. This was explained by the bacterium releasing a “poison” (toxin) which could cause widespread damage to the host (Lax 2005). Since these early days, a very large number of bacterial toxins have been discovered and we now appreciate that many of these proteins are not simple cell or tissue killers, but are precision controllers of cell functionality by specifically targeting host cell surface or intracellular proteins. The infamous clostridial neurotoxins are metalloproteases which target SNARE proteins to influence neuronal function (Popoff and Poulain 2010). Other toxins cause pore formation, inhibit protein synthesis, activate specific intracellular signaling pathways, activate T lymphocytes, and so on (Lax 2005).
A growing number of bacterial moonlighting proteins have functions which would seem to overlap with the actions we would expect from a ‘modern' toxin. The clearest examples of this come from bacteria that target insects. These have evolved to use the molecular chaperone, chaperonin 60, as a toxin. The endosym- biotic bacterium, Enterobacter aerogenes, which exists in the saliva of the doodlebug (a larval form of insects known as the Myrmeleonidae) secretes its chaperonin 60 to be used as an insect neurotoxin by its host (Yoshida et al. 2001). This chaperonin 60 protein is active at nanomolar concentrations. The highly homologous E. coli chaperonin 60 protein, GroEL, has no neurotoxic action, but a single residue mutation can turn this protein into a potent neurotoxin (Yoshida et al. 2001). Various Xenorhabdus species also use their chaperonin 60 proteins as toxins, in this case the target tissue is the gut (e.g., Joshi et al. 2008). Another insecticidal toxin is employed by Paenibacillus larvae which infects larvae of the honeybee (Apis mellifera), causing the condition American Foulbrood. In this condition, the enolase of the bacterium functions as a toxin, being directly toxic to the larvae (Antunez et al. 2011). In addition, the fimbrial subunit of Xenorhabdus nematophila also functions as a pore-forming toxin (Banerjee et al. 2006).
Other proteins with toxin-like actions include the dihydrolip o amide dehydrogenase of Mycobacterium bovis, which binds to the actin-binding protein coronin causes the arrest of phagosome maturation, thus preventing killing of the bacterium within the macrophage (Deghmane et al. 2007) and the Pseudomonas aeruginosa adenylate kinase, which is a secreted cytotoxic factor for macrophages (Markaryan et al. 2001).