For a disease to develop in cereal crops, three basic conditions must be met to create what is known as the disease triangle. Firstly, the crop itself must be susceptible to the disease. Secondly, the crop must encounter the pathogen causing the disease, and thirdly the environmental conditions that promote infection and disease development must be right.

If we start with this last condition, the climate in Ireland is mild and damp and is ideal for wet weather diseases that cause most of the issues in Irish crops. Unfortunately, there is very little that farmers can do about our weather, and it should also be noted these are the same conditions that give Irish crops an advantage in terms of yield potential.

Throughout the last century, cereal production developed to limit exposure of the crop to pathogens and so some of most crippling diseases have been effectively managed – the second component of the disease triangle.

In this same period, seed certification and seed treatments significantly limited the impact of seed-borne diseases. Management, crop rotations and soil fertilisation have also limited the impact of soil-borne diseases.

Combined, these measures have significantly contributed to the increase in yields observed between the 1920s and 1960s. This clearly demonstrates how careful consideration and manipulation of the disease triangle can be used to manage cereal diseases effectively.

Limit foliar infection

Unlike the situation with seed-borne and soil-borne diseases, the ability to restrict exposure to foliar diseases such as septoria or ramularia through crop management practices is limited, although not impossible.

We know that with septoria, windborne ascospores can move within crops and between crops to cause new infections. These ascospores are released from dead crop material and, while they can be detected throughout the growing season, they form the primary source of infection of newly emerged crops in autumn.

To help restrict the development of foliar diseases such as septoria, we need to look either at the host resistance or at creating an environment that isn’t hospitable to the disease. If we could create a resistant host that prevents pathogen infection, that would go a huge way to solving the problem.

While there has been some success in achieving this – given the biology of these diseases and their effective population sizes, which are enormous – the pathogens have a natural ability to overcome resistances.

Furthermore, varieties that have been developed with high levels of resistance to something like septoria have often been deficient in some other trait, whether that be yield, quality or susceptibility to another disease.

Disease protection

So the development and application of fungicides has been an essential strategy in cereal disease management. Fungicides interact directly with the disease triangle by directly inhibiting the pathogen, thus removing it from the equation.

As we use them at particular timings, they also indirectly interact with the host, thus creating an inhospitable environment for the development of the disease.

It must be accepted that fungicides are extremely unlikely to completely inhibit populations of septoria or ramularia in Irish fields.

For this reason, they should be targeted to protect the host at critical timings, corresponding in most instances to the protection of the upper canopy. This creates an environment on these leaf layers that is not conducive to the development of the disease while attempting to maintain satisfactory green leaf area in the crop canopy, especially on the upper leaves which are so significant for grain fill.

Challenge of resistance

By interacting with the different components of the disease triangle, fungicides provide a level of protection against several diseases and allow a certain level of flexibility to be achieved in crop production. However, like host resistance, nature will find ways to survive and as fungicides become increasingly specific, pathogens develop mechanisms to overcome their toxic effects – most commonly referred to as fungicide resistance.

Given the importance of fungicides in Irish cereal production it is important to quantify levels of resistance present in Irish crops, to understand the mechanisms at play and to qualify the risk to the system of resistance development and spread.

Our understanding of fungicide resistance has increased greatly over the past two decades. It is no coincidence that this has overlapped with changes that occurred in the availability and frequency of use of some of the key fungicides used. Although fungicide resistance had occurred prior to the development of the strobilurin issue in the early 2000s, their loss to septoria control was dramatic as they marked a new era in fungicide protection.

This also introduced the concept of fungicide resistance management into the cereal system. This philosophy had become essential to potato late blight management in the early 1980s, following the loss of the phenylamides due to the development of resistance.

Resistance to strobilurins emerged following the development of a single mutation in the target site in the fungus. This mutation, G143A, caused a slight change to the structure of the protein to which the strobilurins bind.

While just a simple change, it had massive implications in how the strobilurins bind to their target.

The change of the amino acid glycine (G) to alanine (A) in the protein at the specific position 143 blocked the fungicide from getting to where it needed to be to lock into and kill the fungus.

Known as target site resistance, this type of fungicide resistance is the most common and often the most dramatic in terms of its ability to inhibit a fungus. For the strobilurin fungicides, this was dramatic. The fact that they were being used extensively across vast areas of wheat and barley, and often alone using high doses, led to rapid selection for resistance.

Almost two decades on, resistance to the strobilurins has remained at extremely high levels. This indicates that this subtle change had extremely low or no impact on the normal functioning of the fungus. But while resistance has rendered the current strobilurins ineffective against diseases such as mildew, septoria and ramularia, these actives still play an important role in the control of cereal rusts and various other foliar diseases on barley, such as rhyncho and net blotch.

Furthermore, as our understanding of the interactions that occur between the fungicide and the target site with G143A improves, researchers at BASF and Sumitomo have been able to develop a new fungicide (metyltetraprole, trade name Pavecto) which is able to circumvent this mutation. This means that this product can overcome strobilurin resistance, bringing hope that this extremely effective mode of action may again become important in wider cereal disease control.

Dependence of the azoles

Following the spread of strobilurin resistance, increased emphasis was again placed upon the azole fungicides for disease control, most notably epoxiconazole and then prothioconazole. In addition, the multisite fungicide chlorothalonil was increasingly included in key applications such as leaf-3 and flag leaf emergence in winter wheat for septoria control, and at awns emerging in barley for ramularia control.

In winter barley, the inclusion of chlorothalonil was primarily used for disease control while in wheat it was a means of managing fungicide resistance.

As the azoles became the key fungicides for control of the main foliar diseases and were commonly applied up to four times per season in wheat, resistance began to emerge as early as 2004.

Initially this was confined to tebuconazole, and to a lesser extent metconazole, with the emergence of the target site mutation I381V. However, additional mutations began to emerge, most notably S524T, and over time this accumulated in strains of the pathogen.

Fortunately, due to the nature of the target site and the diversity of azoles, the various mutations affected the azoles differently. This has been the reason for the concept of alternating the main azoles, epoxiconazole and prothioconazole with metconazole and tebuconazole within a fungicide programme.

However, as we continued to rely on the azoles, mutations have continued to emerge, recombine and accumulate. The effectiveness of the alternation strategy then decreased over time as strains harbouring resistance to both azole groups increased.

Furthermore, additional resistance mechanisms not based on target site mutations have emerged. These have included over-expression of the target site, meaning that there are now strains of septoria with double if not triple the amount of target site to be inhibited.

On top of this, septoria has also developed an ability to pump the fungicide out of itself before it can reach the target site. The combination of less fungicide reaching the target site, more target sites to be inhibited and the reduced ability of the fungicide to bind as the site had changed slightly, have all greatly affected the ability of current azoles to provide control under field conditions. This is now very evident with all four of the above azoles providing similar levels of activity, roughly 40% to 50% control under Irish field conditions.

Molecule sophistication

As with the strobilurins, our knowledge of the interactions between the azoles and their target site has increased and so too has our ability to target them differently. This has culminated in the development of the new azole, Revysol, from BASF.

Currently, this azole provides excellent septoria control, even in crops known to be dominated with strains combining all three resistance mechanisms described previously. However, as is evident from our past, careful consideration must be given as to how we use this azole to ensure we maximise its longevity.

Modes of action

Key to delaying the onset of fungicide resistance is the ability to mix different modes of actions. The arrival of the SDHI fungicides gave us the capacity to implement further fungicide anti-resistance measures at that time. It was then possible to alternate the azole fungicides at key timings, while including an SDHI as an additional mode of action, plus a multi-site.

This undoubtedly delayed the emergence of SDHI resistance and prolonged the moderate levels of azole efficacy observed at that time. However, as was the case previously, the reliance on the SDHIs meant it was inevitable that resistance would again emerge. As was the case with the azoles, multiple levels of resistance emerged.

So far, we seem fortunate that the resistances which have emerged have been moderate in nature. However, they have been rapidly selected and now dominate the Irish septoria population. While numerous target site mutations have emerged, the most dominant ones currently are mutations T79N and N86S in the subunit C of the target site.

Where these mutations dominate, they have led to significant decreases in efficacy, with only 50% of control achievable. When combined with the different azole fungicides, control increases to between 60% and 65%. The inclusion of chlorothalonil increases this further, up to between 80% and 85% control. While these moderate mutations dominate, strains with high levels of resistance conferred by the mutation H152R have also been detected.

To date, these have remained at extremely low levels. However, were these to increase, the efficacy of current SDHIs would be expected to decrease significantly, whether used as solo products or in mixtures with azoles and multisites.

While all the main SDHIs currently available show strong levels of cross-resistance, ie resistance in one affects them all, there are novel SDHIs on the horizon that appear to be able to overcome the current mutations, as is the case with strobilurins and azoles.

Increasing sophistication

As we enter a new era, we see the development of novel chemistries within each main fungicide group. These are either now available (Revysol) or progressing through registration.

We also note the entry to the market of a new mode of action, the QiIs. This represents a unique opportunity to effectively manage fungicide chemistries in a tailored, thought-out process.

Since the demise of the strobilurins, we have been reactive to the development of resistance. However, our ability to do this successfully has been curtailed by the absence of different modes of action with equal levels of efficacy. This is important so that one active can successfully protect another, both in terms of curative activity and persistence of control.

Our efforts to contain resistance development up to now was also hindered by the abundance of varieties with only modest genetic resistance.

Fungicides must be seen as the last tool to be used in the fight against a disease. And when they are used they should be applied at the lowest quantities required to achieve control, and also in mixtures with partners having similar efficacy profiles.

If we acquire these different modes of action as we go forward, we will have the capability of mixing and alternating actives throughout the spray programme. The loss of chlorothalonil, which has provided a lifeline to cereal disease control for the past two decades, must force us to think differently about disease control and in particular about preventing fungicide resistance.