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Iron Requirements of and Acquisition of Iron by Legionella pneumophila, Page 1 of 2
< Previous page Next page > /docserver/preview/fulltext/10.1128/9781555817985/9781555812300_Chap06-1.gif /docserver/preview/fulltext/10.1128/9781555817985/9781555812300_Chap06-2.gifAbstract:
This chapter discusses the current understanding of the relationship between Legionella pneumophila and the metal iron. It summarizes the work of a number of laboratories that demonstrated the importance of iron for Legionella, and highlights recent advances toward uncovering mechanisms of L. pneumophila iron acquisition. The mutant displayed a 42% reduction in hemin binding, confirming that hbp potentiates hemin acquisition by L. pneumophila. Within U937 cells, NU216 and its allelic equivalent NU216R were approximately 100-fold more sensitive than the wild type to treatment with desferoxamine, confirming that they are defective for intracellular iron acquisition. The EDDA-hypersensitive mutant NU208 was also dramatically impaired for replication in U937 cells, and its infectivity defect was exacerbated by treatment of the macrophages with desferoxamine. A reconstruction of the NU208 mutation confirmed that the iron acquisition and infectivity defects were due to the transposon insertion and not a spontaneous second-site mutation. Sequence analysis demonstrated that the transposon disruption lies within a gene that is highly similar to the cytochrome c maturation gene, ccmC. ccmC is generally recognized for its role in the heme export step of cytochrome biogenesis. Quantitative infection assays demonstrated that NU229 was impaired ca. 80-fold in intracellular growth. Reconstruction of the mutant by allelic exchange proved that the defect was due to the inactivation of frgA and not a spontaneous second-site mutation. Subsequently, trans-complementation of the mutation demonstrated that the infectivity defect was directly due to the loss of FrgA.