Data from: Diverse mechanisms of metaeffector activity in an intracellular bacterial pathogen, Legionella pneumophila

Pathogens deliver complex arsenals of translocated effector proteins to
host cells during infection, but the extent to which these proteins are
regulated once inside the eukaryotic cell remains poorly defined. Among
all bacterial pathogens, Legionella pneumophila maintains the largest
known set of translocated substrates, delivering over 300 proteins to the
host cell via its Type IVB, Icm/Dot translocation system. Backed by a few
notable examples of effector–effector regulation in L. pneumophila, we
sought to define the extent of this phenomenon through a systematic
analysis of effector–effector functional interaction. We used
Saccharomyces cerevisiae, an established proxy for the eukaryotic host, to
query > 108,000 pairwise genetic interactions between two
compatible expression libraries of ~330 L. pneumophila‐translocated
substrates. While capturing all known examples of effector–effector
suppression, we identify fourteen novel translocated substrates that
suppress the activity of other bacterial effectors and one pair with
synergistic activities. In at least nine instances, this regulation is
direct—a hallmark of an emerging class of proteins called metaeffectors,
or “effectors of effectors”. Through detailed structural and functional
analysis, we show that metaeffector activity derives from a diverse range
of mechanisms, shapes evolution, and can be used to reveal important
aspects of each cognate effector's function. Metaeffectors, along
with other, indirect, forms of effector–effector modulation, may be a
common feature of many intracellular pathogens—with unrealized potential
to inform our understanding of how pathogens regulate their interactions
with the host cell.