Many bacterial pathogens modulate their hosts through complex arsenals of effector proteins that are injected into host cell during infection. Indeed, the concept that effectors target host proteins and processes to modulate their activities is central to the current molecular understanding of host-pathogen interactions. Legionella pneumophila, the causative agent of a deadly pneumonia known as Legionnaires’ disease, has over 300 effectors, which is the largest known arsenal amongst bacterial pathogens. The sheer size of this arsenal raised the intriguing possibility that several of these proteins might functionally interact once inside the host. To systematically map such interactions, the Ensminger lab leveraged a champion of high-throughput biology, the yeast Saccharomyces cerevisiae, to express each of the 110,000 possible pairwise combinations of L. pneumophila effectors and measure the resulting impact on the eukaryotic cell. This work uncovered several metaeffectors (“effectors of effectors”) that directly modulate the activity of other effectors within Legionella‘s arsenal. Through detailed structural and functional analysis (in collaboration with the Savchenko and Taipale labs), they showed that these activities derive from a diverse range of mechanisms – and suggest that similar interactions may add to the regulatory complexity of other intracellular pathogens.
Full article: http://msb.embopress.org/content/12/12/893
Corresponding News and Views: http://msb.embopress.org/content/13/1/911