Cytochrome c maturation proteins are critical for in vivo growth of Legionella pneumophila.

Legionella pneumophila, an intracellular parasite of macrophages and protozoa, requires iron for extra- and intracellular growth. In a new screen of a mutant library of L. pneumophila for strains defective for growth on agar media lacking supplemental iron, seven mutants were obtained. All of the mutants had a disruption in the cytochrome c maturation (ccm) locus; two had insertions in ccmB, two in ccmC, and three in ccmF. The ccm mutants were unable to multiply within macrophage-like cells (i.e., U937 and THP-1 cells) and Hartmannella vermiformis amoebae. A competition assay in A/J mice revealed that ccm mutants are severely defective for growth within the lung. Taken together, these data confirm that ccm and cytochrome c maturation proteins are required for L. pneumophila growth in low iron, intracellular infection, and virulence.