A Critical New Pathway for Toxin Secretion?

Abstract

Vaccines that are composed of inactivated bacterial toxins work well for diseases such as diphtheria and tetanus, in which a single secreted toxin is the primary mediator of disease. Pathogens that rely on multiple secreted toxins, however, render vaccines impractical, partly owing to the fact that some toxins are directly injected into host cells and are therefore inaccessible to antibody. An alternative approach that is gaining momentum is to target the critical pathways required for toxin secretion. 1 Five distinct protein secretion pathways have been known to contribute to the virulence of bacterial pathogens. Recent studies by the Mekalanos group (Pukatzki et al. 2 and Mougous et al. 3 ) have identified a sixth secretion pathway, present in both Vibrio cholerae and Pseudomonas aeruginosa, that is a potential target for vaccine development and for therapeutic intervention. The classic diarrheal disease resulting from colonization of the small intestine by V. cholerae is mediated by and dependent on the secretion of cholera toxin. Some strains of V. cholerae , such as strain V52, lack the cholera toxin genes but still cause sporadic episodes of cholera-like and nondiarrheal diseases through poorly defined mechanisms. To gain further insight into the pathogenic mechanisms of strain V52, Pukatzki and colleagues 2 established an infection system using amebae. Amebae have macrophage-like properties and can be used to model interactions between bacteria and macrophages.