Although a few intracellular bacterial pathogens, such as Listeria monocytogenes, can replicate within the cytosol of the host cell, most do so within a modified vacuolar compartment. To work out why and how some bacteria replicate in the cytosol when others do not, Goetz et al. used microinjection to circumvent normal phagocytotic uptake of bacteria. Contrary to dogma, they discovered that normally vacuole-dwelling bacteria such as Salmonella enterica and Legionella pneumophila could not replicate when injected directly into the cytosol, unless the host cell was already unhealthy and undergoing apoptosis or necrosis. They also discovered that the only mutants of L. monocytogenes in which cytosolic replication was hindered were those with disruptions in the hpt gene. Hpt encodes an uptake system for phosphorylated sugars and is regulated by the key transcriptional activator for virulence genes, PrfA. Thus, a major constraint to survival in the cytosol appears to be nutrient limitation although, in healthy cells, a role for antibacterial components cannot be ruled out. -- CA
Proc. Natl. Acad. Sci., 10.1073/pnas.211106398.
