Fungicides inhibit fungal growth by interfering with critical cellular processes. Mode of action (MOA) refers to the specific cellular process inhibited by a particular fungicide. FRAC currently lists 11 modes of action in its Mode of Action Poster and Code List (Table 1, column 1). Fungicides may have a mode action that is not fully understood at the time of introduction. Until there is specific evidence of the involved biochemical processes, FRAC list such compounds as “Unknown Mode of Action” in the FRAC code list.
Within each mode of action there are specific sites of action. These sites of action or target sites are the specific enzymes in a cellular process to which the fungicides bide. For example, both strobilurin fungicides and SDHI fungicides share the same MOA (inhibition of respiration) but have different sites of action in the respiratory pathway; SDHIs inhibit complex II while strobilurins inhibit complex III. In pharmaceutical literature the inhibition of a specific enzyme is referred to as the mechanism of action (some plant pathologists use the term mechanism of action interchangeably with mode of action). FRAC assigns compounds active at the same target site a number (e.g. the SDHIs are FRAC group #7 on the FRAC Code list).
To understand the biochemical interaction of the fungicide with a specific target site, the analogy of using a lock and key to open a door is useful. The lock is the target site on the enzyme and the key is the natural substrate the enzyme interacts with to complete normal cellular processes (analogous to unlocking the door). The fungicide(s) active at that target site are an additional set of key-like objects which can also fit into the lock. If one of these “artificial” keys is in the lock, the normal key/substrate cannot fit into the lock and the fungal biochemical process is blocked (the door cannot be unlocked). Inside the cell, the fungicide and the substrate compete for the lock/target site. As the fungicide accumulates in the cell, the normal substrate can no longer access the target site and normal cellular processes will reach such a low level, or may be blocked entirely, that adverse effects are observed. While the fungicides share similarity with the fungal substrate in terms of their three-dimensional structure, they are not identical. It is possible that alterations to the lock/target site could occur that will allow the fungal substrate to continue to bind and normal cellular processes to proceed, but not allow the fungicide(s) to bind (i.e. the lock could be changed such the original key still works to unlock the door but the key-like fungicide no longer fits in the lock). This situation results in one specific type of resistance known as target-site resistance.
Fungicides active at the same target site (i.e. that is within the same FRAC code # on the FRAC Code List) are generally considered to be cross-resistant to each other. Cross-resistance is a phenomenon that occurs when resistance arises to one fungicide that also results in resistance to another fungicide. Occasionally, cross-resistance can occur between compounds active at different target sites (see multi-drug resistance under mechanisms of resistance below). The actual target site is not completely understood for some fungicides so the target site description remains rather generic. For example, the target site description of the azanapthalenes is signal transduction. The two azanapthalenes, quinoyxfen and proquinazid, are grouped together in the same FRAC group since cross resistance was observed in Erysiphe necator. Interestingly, no cross-resistance was observed in another powdery mildew species, Blumeria graminis (Genet and Jaworska, 2009). Negative cross-resistance can also occur. Negative cross resistance is when a change results in a reduction in sensitivity to one fungicide and an increase in sensitivity to another fungicide. For example, isolates of Botrytis cinerea with reduced sensitivity to the benzimidazole fungicides (FRAC group #1 on the FRAC code list) have an increased sensitivity to the N-phenyl carbamates (FRAC group #10 on the FRAC code list; Leroux et al 1989).