Bacterial pathogens exploit a huge range of niches within their hosts. Many pathogens can invade non-phagocytic cells and survive within a membrane-bound compartment. However, only a small number of bacteria, including Listeria monocytogenes, Shigella flexneri, Burkholderia pseudomallei, Francisella tularensis and Rickettsia spp., can gain access to and proliferate within the host cell cytosol. This review discusses the mechanisms by which these cytosolic pathogens escape into the cytosol, obtain nutrients to replicate and subvert host immune responses.
Residing within the cytosol may provide protection for bacteria against certain aspects of host defence, such as recognition by circulating antibodies, the complement system and the microbicidal environment of the phagolysosome. However, it is becoming increasingly clear that pathogens do not entirely escape the human immune system while in the cytosol. A series of intracellular receptors detect microbial pathogen-associated molecular patterns, and have evolved to combat both viral and bacterial pathogens. Although cytosolic pathogens have recently been shown to manipulate autophagic responses, they probably also interfere with many other aspects of host cell signalling to promote their survival within the cell. Therefore, the cytosol provides bacteria with only a limited subset of nutrients and presents them with the formidable challenge of evading an organized system of pathogen recognition mechanisms and responses. Future work will unveil further strategies that bacteria have successfully evolved to survive in and adapt to this specific host niche.