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Molecular genetics has proven to be a useful tool in elucidating, confirming or better understanding fungicide modes of action and mechanisms of resistance. These tools are invaluable in defining new areas of research in the process of discovering fungicides with novel modes of action. In addition, molecular genetics can be used to gain an understanding of the resistance risk of new or known classes of fungicides. In this paper, several areas of resistance research that have relied on these methodologies will be discussed. For example, the strobilurins are known to inhibit activity of the mitochondrial electron transport complex Ill enzyme at the Qo reaction center of cytochrome b. On this protein, electrons are transferred from the low potential cytochrome b566 at the Qo reaction center to the high potential cytochrome b562 at the Qi reaction center. Antimycin A, myxothiazol and other complex lit inhibitors are used as tools to elucidate the nature of these reactions, in large part using molecular techniques. Of the 437 amino acids in cytochrome b, about one fifth are known to have been substituted so far, primarily selected by inhibitor resistance [1]. Several conclusions regarding the mutability of the gene and the fitness of the resistant isolates can be drawn from this research. Thus, our understanding of this target site is greatly enhanced by the wealth of knowledge generated through the molecular genetics of resistance. A second example in which these tools have advanced the knowledge of fungicide resistance mechanisms is in mufti-drug resistance [2]. A number of ATP-binding cassette (ABC) transporters have been identified which are known to play a role in mufti-drug resistance in various yeasts and filamentous fungi, with 16 different ABC genes having been identified in Saccharomyces cerevisiae alone. Using a heterologous probe from one of these genes, two ATP transporters genes were identified from Aspergillus nidulans. Transcription of these genes was enhanced in the presence of azole fungicides, leading to speculation that the ABC transporter's are in some measure responsible for the resistance we see to some classes of fungicides. In this mechanism, overexpression of the transporter's could cause active efflux of the fungicide. Inhibitors of this process could have a profound effect on the ability of plant pathogens to cause disease, opening a new area for a target-based search for novel fungicides. In addition, azole resistance can be due to a target sfte-based mutation in the 14 ademethylase or the A5-6 desaturase of the sterol biosynthetic pathway [3]. At the field resistance level, valuable insight can be gained from understanding the distribution of resistance genes among a population [4]. As this discussion illustrates, the future of our understanding and management of resistance will be increasingly dependent on molecular genetic research.

1. Brasseur G, Saribas AS, Daidal F, 1996. Biochim. Biophys. Acta 1275, 61-69.
2. De Waard MA, 1997. Pesticide Science 51, 271-275.
3. Marichal P, Vanden Bossche H, 1995. Acta Biochim. Polon. 42, 509-516.
4. Adachi Y, Watanabe H, Tsuge T, 1996. Phytopathology 86, 1248-1254.