
Ashley Carlin, communications coordinator for IS-MPMI, recently asked authors Ralph Panstruga and Matthew Moscou questions about their recently published review article addressing one of the MPMI journal’s Top 10 Unanswered Questions, “What is the molecular basis of nonhost resistance?” This Q&A is designed to serve as an entry point for students, and function as a useful tool for teaching. The answers will be used to develop a press release related to the article and disseminate the information to a wider audience.
1) Why were you interested in being a part of the Top 10 Unanswered Questions series, and what attracted you to this question in particular?
When the idea of the Top 10 Unanswered Questions was brought up at the IS-MPMI congress (one of the world’s most important scientific meetings in the area of plant–microbe interactions) in Glasgow, Scotland, in 2019, we were immediately fascinated by the project. Since we both have published expertise in the area of nonhost resistance, it was somewhat self-evident that we could contribute with a review article on this relevant question. We have felt for quite some time that some concepts and terms in the field are ambiguous and possibly misleading and that it would be just the right time to sum up the present knowledge, but also to clarify a few aspects and to raise a few fresh ideas.

2) Why is this an important question to ask?
Scientists, from molecular biologists to plant breeders, have noticed in nature that the majority of pathogens infect only a few species. This long-standing phenomenon has driven the motivation to study the interaction of plants and pathogens that do not normally infect them. Often this motivation is pragmatic. There are several plant species that have little, if no, resistance to a pathogen. Observing that closely related species may be resistant, scientists have been motivated to identify the biological process that makes these plants resistant. This motivation can also be more fundamental, stemming from the desire to understand the relationship between resistance to a pathogen that typically infects a plant versus related pathogens that never infect a plant. By uncovering the mechanism underlying resistance, it not only helps our understanding of the plant immune system, but it may uncover previously unknown aspects of immune signaling and regulation. Scientists ultimately hope to be able to transfer part of this knowledge into improved disease resistance against a broader spectrum of pathogens.
3) Why is this an important question to ask now?
Plant pathogens are a persistent threat to agriculture. They limit how much food is produced, where we can grow crops, and increase food waste (how many times have your strawberries become infected by grey mold?). Science has contributed substantially to reducing the impact of disease, through the development of pesticides, altering cultural practices in the field to limit the development of disease, and breeding resistance from wild crop ancestors into elite crop cultivars. Despite these efforts, the modern world undermines some of these efforts; for example, the greater accessibility to global transport around the world has contributed to the movement of plant pathogens into new environments. The field of nonhost resistance, guided by approaches that already exist in nature, sets out to identify novel ways to engineer resistance to these plant pathogens. Another aspect that makes this question a timely one is the occurrence of new plant diseases due to globalization and agricultural practices (e.g., extended monocultures). A prominent example is the recent emergence of wheat blast disease caused by the fungus Magnaporthe oryzae, which for a long time was unable to colonize wheat.

4) What are some of the things we know about this topic, and what are some important things we don’t know?We have learnt over the last two to three decades that nonhost resistance is usually a multigenic trait (i.e., a feature controlled by many genes). It is largely governed by the characteristic attributes of a given plant-pathogen constellation. Pre-existing and induced physical barriers (such as the plant cuticle, a waxy covering of the epidermis) and the secretion of antimicrobial molecules (such as toxic metabolites or defense-associated peptides) are often key factors in nonhost plant resistance. More recently, scientists have recognized the interplay of host NLR-type immune sensors and secreted pathogen effector proteins as another important determinant of nonhost resistance. NLR-type immune sensors were assumed for a long time to play a role primarily in resistance to adapted plant pathogens, while their role in defeating nonadapted (“nonhost”) pathogens was less clear. Altogether, this led to the insight that nonhost resistance essentially is a phenomenological concept that mechanistically relies on the regular armory of the plant immune system that is also active against adapted pathogens. Examples of conditional (e.g., temperature- or tissue-dependent) nonhost resistance have been described more recently, and it has become clearer that disease susceptibility and nonhost resistance are the extreme ends of a continuum, with many possible intermediate outcomes. Accordingly, due the presence of cryptic infections, we are probably not yet aware of the full host range of some pathogens. While the contribution of microbial commensals (microbes that naturally inhabit plant organs without causing any harm) to plant immunity has emerged during the past few years, their explicit role in nonhost resistance has not been demonstrated yet. Finally, our knowledge on nonhost resistance largely relies on findings obtained in a handful of (model) angiosperm plant species that are genetically very tractable. We do not know yet to what extent these insights can be generalized, especially with respect to nonangiosperms.
5) Why don’t we have the answer yet—what have been some of the roadblocks?
We usually only appreciate plant diseases when they become visible to the naked eye, i.e., in the form of more or less severe disease symptoms (e.g., wilted leaves or fungal colonies on the plant surface). Cryptic infections are invisible to the naked eye and might be hard to detect even under a microscope. DNA sequencing methods may help to recognize the undetected presence of pathogenic plant invaders. This requires ultradeep sequencing, which only became available more recently. To test the contribution of microbial commensals to nonhost resistance, we need reconstitution experiments with synthetic microbial communities (i.e., communities experimentally composed by in vitro-grown microbes) in combination with germ-free plant systems. These tools were established only recently for some model plant species and are not yet available for many agriculturally important crop plant species.
6) What are the most recent advancements in this area?
As stated above, the contribution of NLR-type immune sensors to nonhost resistance is a comparatively recent insight. So far, their involvement has only been demonstrated in nonhost plant species that are closely related to the host species of a given pathogen and to nonadapted pathogen species that are closely related to an adapted pathogen species. It remains to be seen whether their participation in nonhost resistance can also be validated for more distantly related plant and pathogen species.
7) If we were able to answer this, what might we learn?
We will appreciate better that susceptibility and resistance are the extreme outcomes of interactions between plants and pathogens, with all kinds of intermediate forms possible. We may also get to know yet undiscovered “reservoirs” of plant pathogens on some plant species, which can help to sustain disease on crop plants. If they exist, it will be important to incorporate their existence into any strategy to control a plant pathogen. We will further comprehend whether microbial commensals also contribute to resistance against nonadapted pathogens, which could form the basis for future plant protection measures. Finally, these insights will complete our picture of the plant immune system.
8) Is there anything else you’d like to tell me about this question?
This question is fundamental to understanding why some plants get infected by a particular pathogen and others do not and, vice versa, why a given pathogen can only successfully colonize a limited number of plant species, which collectively form its “host range.”
















