The paper is an extensive review of discoveries concerning plant disease resistance proteins. It is highly cited probably because plant disease resistance research is an exciting and fast-moving field, of urgent practical importance in agriculture, of fundamental biological interest, and of increasingly clear relevance to innate immunity in animals. Cloning of the first plant disease resistance (R) gene was published just 11 years prior to this paper, and we list over 40 R genes cloned since then in our paper. Despite the diversity of plant species from which these genes have been cloned, and the diversity of signals from pathogenic fungi, bacteria, viruses, and animals (nematodes) to which they collectively mediate resistance responses, the encoded proteins largely fall into a limited number of structural classes. A handful of these have developed into powerful models for understanding 1) pathogen recognition and 2) signaling that lead to defense. In addition to providing a broad review of R protein-related discoveries, our paper provides a detailed discussion of both of these areas. In particular, it critically examines published models, and new alternative models for the molecular basis of pathogen recognition. This examination includes specific, testable predictions that we hoped would help stimulate further hypothesis-driven research in this area. Also, the signaling section in particular highlights the many developing parallels with signaling in animal defense against pathogens, and paints a clear picture both of shared signaling mechanisms and mechanisms unique to particular classes of R proteins. Finally, the paper is of interest because, while it makes clear the rapid progress of the field that has resulted from a progression from classical pathology to genetics and molecular biology into cell biology and biochemistry, it also summarizes the key gaps in our understanding and points to the promise of functional genomics, proteomics, and future innovative research for continued progress.

By reference to published papers, yes, this review offers a broad view of important recent discoveries and useful methods in R protein and related research.

The paper presents our current understanding of how plants defend themselves against microbial attack that would otherwise lead to disease. This research area is important for practical purposes in order to develop better approaches to controlling losses in our food and fiber production that occur due to disease. It is also important because it contributes to our fundamental understanding of plant and microbial biology, and may have implications for human health and medicine. Plant disease resistance research is a fast-moving field. This paper is useful because it provides both an extensive review of recent discoveries, and a summary of important areas and methods for future research.

Gregory Martin (Scientist, Boyce Thompson Institute and Professor of Plant Pathology, Cornell University): I originally became interested in plant disease resistance in 1982 when I witnessed the effects of a halo blight disease outbreak on field beans in East Africa where I was working with USAID to catalog biodiversity of landraces. The outbreak significantly reduced the bean harvest that year and, because this crop was a principal source of protein, it further exacerbated the malnutrition of the subsistence farmers and their families. My research interests evolved from this experience and are now directed at understanding the molecular basis of bacterial pathogenesis and plant responses to bacterial pathogens. I hope this knowledge eventually will be used to develop new strategies to reduce the impact of plant diseases, especially in developing countries.

Adam Bogdanove: After graduating from college, I worked for a while in Japan, a country with intensive agriculture, and an emerging leader in environmental stewardship. During that time, I became interested in the promise of plant disease resistance research for reducing our dependence on potentially environmentally damaging chemicals to control plant pests and diseases. I returned to the US then to study molecular plant pathology, and began my career in this field.

Guido Sessa: When I first arrived in Israel I worked in a kibbutz as an agriculturist becoming familiar with pest management and plant protection practices related to growth of cotton and other plant species. This field experience raised my interest in the way plants defend themselves against pathogens and in the possibility of using plant natural defenses for the development of new disease-control strategies.