If Legionella pneumophila — an aquatic bacterium that infects protozoan hosts in freshwater ecosystems — is inhaled by humans, it causes a severe form of pneumonia known as Legionnaires' disease. Once in the lungs, L. pneumophila is internalized into the phagosomes of alveolar macrophages. However, rather than being degraded by the macrophage lysosome, this bacterium makes itself at home. It hijacks host vesicle trafficking to make an endoplasmic reticulum (ER)-derived vacuole that supports its replication. So, how does it do it?

New insights are now reported by Kagan and Roy in Nature Cell Biology. They began by showing that L. pneumophila-containing phagosomes mature into ER-derived vacuoles in a biphasic manner. First, they interact with early secretory vesicles — vesicles travelling from the ER to the ER–Golgi intermediate compartment (ERGIC); then, they acquire markers that are concentrated in the ER. But, how do they get to the ER?

Cholera and Shiga toxins are known to reach the ER using a pathway that takes them through the Golgi, but Kagan and Roy show that L. pneumophila-containing phagosomes do not interact with intermediate compartments (the Golgi or ERGIC). Instead, they found that these phagosomes interact directly with transitional ER (tER) sites — dynamic sites where early secretory vesicles exit the ER — and that L. pneumophila forms an ER-derived vacuole by subverting vesicular transport from these sites. In addition, they showed that the subversion of early secretory vesicles is required to make a stable vacuole that is kept sequestered from the endocytic pathway.

Therefore, Kagan and Roy have shown that L. pneumophila subverts host cellular processes in a new way, and they suggest that understanding the mechanisms that are used by this bacterium to interact with tER sites and to recruit ER-derived vesicles might help us to identify host factors that regulate vesicular transport at these sites.