Identification of immunogenic microbial patterns takes the fast lane.

I nnate immunity to microbial infection is an inherent feature of all multicellular eukaryotes. In contrast to jawed vertebrates, which, in addition to innate defenses, also possess noninheritable mechanisms of adaptive immunity, antimicrobial defenses of lower metazoans and plants are germline-encoded. Plants use a bipartite immune system to cope with infection (1). The evolutionarily older branch is based on recognition of common microbe-associated molecular patterns (MAMPs) by plant pattern recognition receptors (PRRs) or upon recognition by PRR-type receptors of hostderived damage-associated molecular patterns that are produced by deleterious microbial enzymatic activities or toxins (2). This type of plant immunity is referred to as MAMP-triggered immunity (MTI), and is equivalent to metazoan innate immunity. A second, evolutionarily younger, layer of plant immunity is referred to as effector-triggered immunity, which is based on the recognition of the presence or activities of microbial pathovar-specific effector proteins by cognate plant immune receptors (3). Despite intense efforts to identify immunogenic molecules from a wide variety of microbial sources, remarkably few such structures have been described so far. Past approaches were based almost exclusively on biochemical purification procedures, but have often proven difficult, for example, because of major autolysin activities in bacterial materials. Likewise, although several microbial patterns (e.g., bacterial flagellin, lipopolysaccharide, peptidoglycan) trigger immune responses in metazoans and plants, systematic testing agonists of metazoan PRRs as elicitors in plants was little rewarding, likely because host sensors for microbial patterns have evolved independently in different lineages (4). In those cases, however, when elicitor isolation was successful, immunogenic activity could be ascribed to small, epitope-like motifs (reviewed in ref. 2; Table 1). In PNAS, McCann et al. (5) describe an exciting genomics-based bioinformatic strategy to identify proteinaceous microbial signatures triggering plant defense. This approach is built on two assumptions. First, hosts are likely to evolve recognition systems for “core” microbial structures that represent vital cellular functions, are broadly conserved among microbial species or genera, and are not subject to frequent mutation. Indeed, known MTI elicitors were shown to exhibit such features (6). The authors propose that these sequences are found preferentially in proteins that are under strong negative selection and that are characterized by low rates of nonsynonymous amino acid exchanges. The second assumption of the