Different pathogens have distinct strategies for altering membrane traffic in the host cell (Figure 23–24). M. tuberculosis prevents the early endosome that contains the bacteria from maturing, so the endosome never acidifies or acquires the other characteristics of a late endosome or lysosome. This strategy requires the activity of its type VII secretion system, as well as mycobacterial lipid products that mimic host lipids and influence vesicular traffic. Phagosomes containing Salmonella enterica, in contrast, acidify and acquire markers of late endosomes and lysosomes, but the bacteria slow the process of phagosomal maturation. They do so by injecting effector proteins through a second type III secretion system. These effectors activate host kinesin motor proteins to pull membrane tubules outward from the phagosome along cytoplasmic microtubules, forming a specialized compartment called the Salmonella-containing vacuole (Figure 23–25).
Other bacteria seem to find shelter in intracellular compartments that are distinct from those of the usual endocytic system. One example is Legionella pneumophila, which was first recognized as a human pathogen in 1976, when it was found to be the cause of a type of pneumonia known as Legionnaire’s disease.
L. pneumophila is normally a parasite of freshwater amoebae, but it is commonly
Figure 23–24 Modifications of membrane traffic in host cells by bacterial pathogens. Intracellular bacterial pathogens, including Mycobacterium tuberculosis, Salmonella enterica, and Legionella pneumophila, all replicate in membrane-enclosed compartments, but the compartments differ. M. tuberculosis remains in a compartment that has early endosomal markers and continues to communicate with the plasma membrane via transport vesicles. S. enterica replicates in a compartment that has late endosomal markers and does not communicate with the plasma membrane. L. pneumophila replicates in an unusual compartment that is wrapped in rough endoplasmic reticulum (ER) membrane and communicates with the ER via transport vesicles. TGN, trans Golgi network.
Figure 23–25 Salmonella enterica residing in a modified phagosomal compartment called the Salmonella-containing vacuole. These bacteria invade the host cell using an SPI1 type III secretion system to inject effector proteins that induce the trigger mechanism of microbe entry illustrated in Figure 23–19B.
Following its engulfment into a phagosome, the bacterium inactivates its SPI1 type III secretion system and activates its SPI2 type III secretion system to inject different effector proteins, which remodel the phagosome into the specialized Salmonella-containing vacuole. One of the injected effector proteins activates host kinesin motor proteins to pull membrane tubules outward toward the plus ends of the microtubules (see Figure 16–42). (B) Fluorescence micrograph showing
S.
enterica in a Salmonella-containing vacuole. The bacteria are stained green, the microtubules red, and the nucleus blue. (B, courtesy of Stephane Meresse.) blocking of type IV secretion 0.5 µm