MOLECULAR PLANT PATHOLOGY (2001) 2 (2), 109–115 © 2001 BLACKWELL SCIENCE LTD 109 Blackwell Science, Ltd Review Targeting the targets of Type III effector proteins secreted by phytopathogenic bacteria ROGER W. INNES Department of Biology, Indiana University, Bloomington, IN 47405 -3700, USA INTRODUCTION Many Gram-negative bacterial pathogens of both plants and animals depend on a type III secretion system to infect their host organism (Hueck, 1998). Type III secretion systems have been most intensively studied in species of Yersinia and Salmonella, where it has been established that they function to inject multiple effector proteins directly into host cells (Hueck, 1998). In mammalian cells, these effector proteins interact physically with specific signal transduction proteins, leading to multiple changes in host cell physiology, including major alterations in the actin cytoskeleton, suppression of immune responses, and activation of apoptosis (programmed cell death) (Cornelis, 2000; Galan and Zhou, 2000). By comparison, very little is known about the function of effector proteins secreted by plant pathogens. However, several recent papers are beginning to shed new light. I will discuss the implications of these new papers and discuss some promising new directions for elucidating the function of effector proteins secreted by plant pathogens. BACKGROUND Although the function of the type III secretion system was first elucidated in animal pathogens (Cornelis, 2000), genes encoding the components of type III systems were first identified in the plant pathogen Pseudomonas syringae pv. phaseolicola (Lindgren et al., 1986). In this early work, several P. s. pv. phaseolicola mutants were identified that failed to induce a hypersensitive resistance response on tobacco, a non-host. Importantly, these mutants also failed to cause disease on their normal host, bean. Mutations in several different genes, which were clustered in a small interval of DNA, gave rise to this phenotype. This cluster was designated the hrp cluster for h ypersensitive r esistance and p athogenicity. The mechanistic basis of this phenotype did not become clear until 6 years later, when the first gene sequences from the Yersinia type III secretion apparatus were published and recognized to be homologous to hrp genes from P. syringae, Xanthomonas campestris pv. vesicatoria and Pseudomonas solanacearum (now known as Ralstonia solanacearum ) (Fenselau et al., 1992; Gough et al., 1992). This observation indicated that protein secretion by phytopathogenic bacteria is an essential aspect of both patho- genesis and the induction of host defence responses. Establishing the mechanistic links between type III effectors (proteins secreted by the type III system), pathogenesis, and induction of the HR in plants has been difficult. Most putative type III effectors from phytopathogenic bacteria were first iden- tified genetically as the products of classical avirulence ( avr ) genes. Avirulence genes in bacteria are defined as genes that can convert a normally virulent strain to avirulence in a host-specific manner. Avirulence is usually manifested as an induction of an HR on resistant host plants. Because induction of the HR is depend- ent on hrp genes, it was hypothesized that the products of avr genes are secreted by the type III secretion system directly into the cytoplasm of host cells. Compelling data supporting this hypothesis have been provided by expressing avr genes directly inside plant cells using transient delivery methods and/or expression under an inducible promoter (Bonas and Van den Ackervaken, 1997). In all cases, the expression of an avr gene inside a plant cell leads to induction of an HR-like response (i.e. cell death) that is dependent on a cognate disease resistance ( R ) gene in the plant. It is thus assumed that the hrp secretion system’s only role relative to HR induction is the delivery of Avr proteins into plant cells; however, direct proof of such protein translocation is yet to be obtained. The existence of specific type III effectors in phytopathogenic bacteria that induce strong defence responses in plants is para- doxical, unless they also play a role in pathogenesis. Surprisingly, the first avr genes identified, which were in the soybean patho- gen P. syringae pv. glycinea, appeared to make no significant contribution to pathogenesis; mutation of these genes did not affect the virulence of these strains on normally susceptible hosts, and many P. syringae strains completely lacked these avr genes (Staskawicz et al., 1984; Staskawicz et al., 1987). Many other avr genes have been identified subsequently, and several do indeed Correspondence : Department of Biology, 1001 East Third Street, Jordan Hall 142, Indiana University, Bloomington, IN 47405-3700, USA. E-mail: rinnes@bio.indiana.edu