Pesticide resistance: Can we make it a renewable resource?

Negative cross-resistance (NCR) occurs when a mutant allele confers {i) res istance to one toxic chemical and (ii) hyper-susceptibility to another. Seq uential deployment of NCR toxins is useful for insect control in few situat ions {Pittendrigh et at., 2000). Using Monte Carlo simulations, we investig ated the concurrent use of a pair of NCR toxins to control a hypothetical i nsect pest population. When the toxins killed more heterozygotes than homoz ygotes, the resistance allele became either extremely common or rare depend ing on starting allelic frequency. if the NCR toxins did not kill the two h omozygous groups equally, then the toxin with lesser toxicity eventually pl ayed a greater role in the control of the pest population. Based on our res ults, we present an approach for the systematic development of an NCR toxin after the commercial release of the first toxin. First, large-scale screen s are performed to find chemicals that kill the resistant homozygous insect s, but not the susceptible ones. Chemicals that preferentially kill resista nt insects are then tested for toxicity to the heterozygotes. Those highly toxic to both homo- and heterozygotes are given the highest priority for de velopment. This screen can be adapted to identify compounds useful in contr olling antibiotic-, herbicide- or fungicide-resistant organisms. (C) 2001 A cademic Press.