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. 2005 Jul;187(14):4853–4864. doi: 10.1128/JB.187.14.4853-4864.2005

FIG. 5.

FIG. 5.

Model of P. aeruginosa cellular events that could occur upon exposure to As(III). 1. The main defense against As(III) exposure is induction of the arsR-arsB-arsC operon, encoding the ArsR repressor, the ArsB anion translocator, and the ArsC As(V) reductase (12). Prior to As(III) exposure, the ArsR repressor prevents transcription of the arsB and arsC genes. 2. Upon entry of As(III) via potentially a homolog of the mammalian GlpF aquaporin that is also present in E. coli (55), the ArsR repressor binds As(III) and no longer acts as a repressor, allowing for synthesis of ArsB and ArsC. 3. ArsB then extrudes As(III) from the cell. 4. If the cell is exposed to arsenate [As(V)], ArsC reduces As(V) to As(III), which is then extruded by ArsB. 5. In an arsB mutant, As(III) accumulates and then depletes the reduced glutathione (GSH) pools that are essential to keep sulfhydryl groups on proteins reduced. As(III) would also oxidize the same sulfhydryl groups being reduced by GSH. 6. Example: the sulfhydryl groups on the lipoamide arms of the pyruvate dehydrogenase complex (PDH) which is sensitive to As(III) at micromolar levels (36). 7. In wild-type cells, the role of SOD is to detoxify O2−. 8. However, in a sodA sodB mutant, elevated concentrations of O2− can react with GSH to form GSSG and sulfonate (88), reducing the cells' capacity to protect against As(III) exposure. 9. O2− can also react with many [4Fe-4S]-containing enzymes, such as aconitase and fumarase, and thus inhibit the TCA cycle. 10. This causes oxidation of the iron in the cluster, rendering the cluster unstable. This results in the release of reactive iron (Fe2+) in the cytoplasm. The Fe2+ is then free to react with H2O2 in a Fenton reaction to form the very destructive hydroxyl radical (HO·). 11. Putative regulatory function of Crc in response to As(III) exposure. Loci potentially regulated by Crc are compressed together to conserve space in this figure but are not transcriptionally linked, as might be inferred by their adjacent location as depicted in the figure.