In the absence of metal, it is a weakly associated dimer and that binding of the first metal ion induces a conformational change that facilitates the binding of a second metal ion to the complex, resulting in stabilization of the dimeric complex and activation of its repressor function. Active DtrR binds to a 27bp palindromic sequence upstream of the tox gene. V. Vaccine and therapy Toxoid is generated by treatment of DT with dilute formaldehyde. Toxoid is devoid of toxicity but is virtually indistinguishable antigenically from toxin. In the U.S. two doses are given one month apart to infants 3-4 months of age with a booster one year later.
Current vaccines use a DT with specific mutations that render it non-enzymatically active.
Toxin is produced from same the strain isolated in 1896. Strain lacks secreted sideropore, corynebactin. Vaccine is extremely effective that requires public health policies and compliance. An example of breakdown in public health policies is currently occuring in Russia where there have been major recent outbreaks of Diphtheria. Because this problem was essentially solved so early in the history of microbiology, many unanswered questions regarding pathogenesis and immunity remain.