The toxin complex (tc) genes of bacteria comprise a large and growing family 
whose mode of action remains obscure. In the insect pathogen Photorhabdus, tc 
genes encode high molecular weight insecticidal toxins with oral activity 
against caterpillar pests. One protein, TcdA, has recently been expressed in 
transgenic plants and shown to confer insect resistance. These toxins therefore 
represent alternatives to toxins from Bacillus thuringiensis (Bt) for deployment 
in transgenic crops. Levels of TcdA expression in transgenic plants were, 
however, low and the full toxicity associated with the native toxin was not 
reconstituted. Here we show that increased activity of the toxin TcdA1 requires 
potentiation by either of two pairs of gene products, TcdB1 and TccC1 or TcdB2 
and TccC3. Moreover, these same pairs of proteins can also cross-potentiate a 
second toxin, TcaA1B1. To elucidate the likely functional domains present in 
these large proteins, we expressed fragments of each 'toxin' or 'potentiator' 
gene within mammalian cells. Several domains produced abnormal cellular 
morphologies leading to cell death, while others showed specific phenotypes such 
as nuclear translocation. Our results prove that the Tc toxins are complex 
proteins with multiple functional domains. They also show that both toxin genes 
and their potentiator pairs will need to be expressed to reconstitute full 
activity in insect-resistant transgenic plants. Moreover, they suggest that the 
same potentiator pair will be able to cross-potentiate more than one toxin in a 
single plant.