Function of Legionella Effectors

The availability of a variety of genetic tools, a complete genome sequence, and several convenient host systems offers the opportunity to study the molecular mechanisms of the interactions between Legionella and its hosts. Examination of the Legionella genome sequence revealed the existence of a relatively large number of genes that resemble eukaryotic rather than prokaryotic orthologs. Alternative approaches based on genome inspection or the use of clever genetic screens for other phenotypes eventually led to the identification of several effectors. In one case, Legionella effectors that vaguely resemble components of vesicle fusion proteins (e.g. EEA1, interaptin) were shown to play a role in a previously recognized nonlytic release pathway in protozoa that results in packets of bacteria being exocytosed prior to host cell death. Frustrated by the lack of information based on classical genetic approaches, researchers sought to examine the genome for additional clues using more targeted approaches than the original BLAST-based annotation. The majority of leg gene products appear to contain motifs involved in protein:protein interactions such as ankyrin repeats, leucine-rich repeats, or coiled coils. A combination of bioinformatics and novel genetic approaches has resulted in the identification of several interesting translocated effectors. The challenge is now to determine how these effectors alter host cell organelle trafficking.