“…Acidification is achieved by pumping protons into the vacuole, and achieving lower pHs against an ever-increasing acidity gradient could prove thermodynamically difficult. There is also evidence that the integrity of the cell membrane lipid bilayer is compromised by acidity at a pH of 3 and below (61,62), which could promote leakage of phagolysosomal contents into the cytoplasm with damage to the host cell. Consequently, we propose that a larger variation in macrophage phagolysosomal pH acts as a diversified bet-hedging strategy against the stochasticity of the potential pH tolerances of ingested microbes within the physiological limits of achievable acidification.…”