Affecting the Effectors: Regulation of Legionella pneumophila Effector Function by Metaeffectors

Many bacterial pathogens utilize translocated virulence factors called effectors to successfully infect their host. Within the host cell, effector proteins facilitate pathogen replication through subversion of host cell targets and processes. Legionella pneumophila is a Gram-negative intracellular bacterial pathogen that relies on hundreds of translocated effectors to replicate within host phagocytes. Within this large arsenal of translocated effectors is a unique subset of effectors called metaeffectors, which target and regulate other effectors. At least one dozen metaeffectors are encoded by L. pneumophila; however, mechanisms by which they promote virulence are largely unknown. This review details current knowledge of L pneumophila metaeffector function, challenges associated with their identification, and potential avenues to reveal the contribution of metaeffectors to bacterial pathogenesis.