How does the oxidative burst of macrophages kill bacteria? Still an open question

Abstract

Reactive oxygen species (ROS) are critical components of the antimicrobial repertoire of macrophages, yet the mechanisms by which ROS damage bacteria in the phagosome are unclear. The NADH-dependent phagocytic oxidase produces superoxide, which dismutes to form H(2)O(2). The Barras and Méresse labs use a GFP fusion to an OxyR regulated gene to show that phagocyte-derived H(2)O(2) is gaining access to the Salmonella cytoplasm. However, they have also shown previously that Salmonella has redundant systems to detoxify this H(2)O(2). Although Salmonella propagate in a unique vacuole, their data suggest that ROS are not diminished in this modified phagosome. These recent results are put into the context of our overall understanding of potential oxidative bacterial damage occurring in macrophages.

Figure 1. Reactive oxygen species in the Salmonella containing vacuole

The phagocytic oxidase (Phox) produces O₂⁻ which enters the periplasm through porins or perhaps crosses the outer membrane that is partially permeabilized by antimicrobial peptides. This superoxide potentially kills or inhibits cells by reducing or oxidizing unknown targets. SodCI protects the cell by dismuting superoxide to hydrogen peroxide, which can freely diffuse across membranes into the cytoplasm. This species can cause the same damage as endogenously produced peroxide, all via Fenton chemistry. However, Salmonella produces six catalases or peroxidases that are capable of keeping the peroxide levels below 5 μM. The SCV is created by the action of SPI2 effector proteins injected into the macrophage cytoplasm that block vesicular trafficking and lessen the delivery of antimicrobial compounds. The assembly of Phox on the phagosomal membrane might also be decreased, but not to an extent that has phenotypic consequences. The shown chemical reactions are not necessarily balanced.