Tripping on Acid: Trans-Kingdom Perspectives on Biological Acids in Immunity and Pathogenesis
Figure 5
Coxiella and Brucella use distinct mechanisms for intracellular pathogenesis.
A. C. burnetti thrives in the acidic phagolysosome system, requiring low pH for the transition from quiescent small cell variants (SCV) to metabolically active large cell variants (LCV). Several of the transmembrane proteins that mark the Coxiella-containing vacuole (CCV) through this transition are shown. The Dot/Icm type IV secretion system is used by C. burnetti to deliver proteins into the host cytosol [138], and renovate the lysosome into a CCV [139]. Cb, Coxiella burnetti; Atg, autophagosome; Lys, lysosome. B. Working model of Brucella intracellular parasitism. Brucella-containing vacuoles avoid fusion with acidic lysosomes, and instead traffic to a compartment that is decorated with ER markers for replication. The Type IV secretion system (T4SS) of the pathogen is critical for appropriate trafficking, and mutants that harbor mutations in the T4SS traffic to the lysosome where they are killed. Several T4SS secretion substrates have been identified, and it has been postulated that these molecules contribute to supporting the intracellular lifestyle of the pathogen. Replicative Brucella can exit cells by trafficking along a pathway that involves selective interactions with components of the host cell autophagy biogenesis machinery. Approximate vesicular/vacuolar pH is indicated by color, and the Golgi is generally more acidic than the ER [57, 140–142].