Legionella pneumophila is an aquatic bacterium that infects protozoan hosts in freshwater ecosystems. However, if it is inhaled by humans it causes a severe form of pneumonia known as Legionnaires' disease. It is an intracellular pathogen that hijacks host vesicle transport to make a vacuole that supports its replication, and this replication occurs in phagocytes in humans.

Vacuole biogenesis requires the bacterial Dot/Icm transporter — a type IV protein secretion apparatus. Bacterial proteins are thought to translocate, through Dot/Icm, across the membrane of the phagosome — the membrane-bound vesicle that surrounds the bacteria after phagocytosis — into the host cell. These bacterial proteins can then act to alter vesicle transport.

The injected proteins have remained elusive, but now, reporting in Science, Roy and colleagues describe the identification of RalF, a bacterial protein that is injected into the host cell through Dot/Icm.

The authors showed that RalF is required for the recruitment of the host protein ADP ribosylation factor 1 (ARF1) to Legionella phagosomes. ARF1 is an important regulator of vesicle transport from the endoplasmic reticulum to the Golgi. It is a GTP-binding protein, and the authors showed that, using its Sec7-homology domain, RalF functions as an ARF guanine nucleotide exchange factor.

As the Sec7-homology domain in RalF is only the second to be identified in prokaryotes, and the authors could not identify the ralF gene in any other Legionella species, they speculated that its presence in L. pneumophila is likely to have resulted from horizontal gene transfer. They hypothesized that genes acquired recently, encoding proteins secreted by Dot/Icm, might enhance bacterial replication in new environments and might also increase bacterial virulence. In the future, identification of additional Dot/Icm substrates will enable us to further understand how an environmental organism has become a human pathogen.