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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iron is required for the intracellular and extracellular growth of Legionella pneumophila (Lp). In addition, variations in iron levels may serve as a signal for changes in gene expression. In a number of bacterial pathogens, the regulation of gene expression by iron is usually mediated by the Fur (ferric uptake regulation) repressor protein. Through complementation of an Escherichia coli fur mutation and nucleotide sequence analysis, we have cloned and characterized the Lp fur gene. Lp fur encoded a 15.0-kDa protein whose repressive activity was, as expected, highest in bacteria grown in iron-rich media. Computer analysis determined that Lp Fur had an amino-acid identity of over 54% and a similarity of over 72% to the Fur of E. coli, Yersinia pestis, Vibrio species and Pseudomonas aeruginosa. The promoter region of Lp fur contained sequences homologous to the Fur-binding site, suggesting that fur is autoregulated in Lp. Finally, Southern blot hybridizations demonstrated that fur is conserved among Lp strains and Legionella species.
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PMID:Cloning and sequencing of the Legionella pneumophila fur gene. 820 May 25

Legionella pneumophila, a parasite of alveolar macrophages, requires iron for intra- and extracellular growth. Although its mechanisms for iron assimilation are poorly understood, this bacterium produces Fur, a protein that can repress gene transcription in response to iron concentration. Because iron- and Fur-regulated genes are important for infection in other bacteria, the identification of similar genes in L. pneumophila was undertaken. A wild-type strain of L. pneumophila was randomly mutated with a mini-Tn10' lacZ transposon, and the resulting gene fusions were tested for iron regulation by assessing beta-galactosidase production in the presence and absence of iron chelators. Of the initial six mutants with iron-repressed lacZ fusions, two strains, NU229 and NU232, possessed fusions that were stably iron regulated. To assay for Fur regulation, the levels of beta-galactosidase were measured in strains no longer producing Fur. As in a number of pathogenic bacteria, L. pneumophila fur could not be insertionally inactivated, but spontaneous Fur- derivatives were generated by selecting for manganese resistance. Strain NU229 contained a Fur-repressed fusion based on derepression of lacZ expression in its manganese-resistant derivative. Extracellular growth of NU229 in bacteriological media was similar to that of wild-type strain 130b. To assess the role of an iron- and Fur-regulated (frgA) gene in intracellular infection, the ability of NU229 to grow within U937 cell monolayers was tested. Quantitative infection assays demonstrated that intracellular growth of NU229 was impaired as much as 80-fold. Reconstruction of the mutant by allelic exchange proved that the infectivity defect in NU229 was due to the inactivation of frgA and not to a second-site mutation. Subsequently, complementation of the interrupted gene by an intact plasmid-encoded gene demonstrated that the infectivity defect was due to the loss of frgA and not to a polar effect. Nucleotide sequence analysis revealed that the 63-kDa FrgA protein has homology with the aerobactin synthetases IucA and IucC of Escherichia coli, raising the possibility that L. pneumophila encodes a siderophore which is required for optimal intracellular replication. Southern hybridization analysis determined that frgA is specific to L. pneumophila.
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PMID:An iron- and fur-repressed Legionella pneumophila gene that promotes intracellular infection and encodes a protein with similarity to the Escherichia coli aerobactin synthetases. 897 3

Legionella pneumophila, a facultative intracellular parasite of human alveolar macrophages and protozoa, causes Legionnaires' disease. Using mini-Tn10 mutagenesis, we previously isolated a L. pneumophila mutant that was hypersensitive to iron chelators. This mutant, NU216, and its allelic equivalent, NU216R, were also defective for intracellular infection, particularly in iron-deficient host cells. To determine whether NU216R was attenuated for virulence, we assessed its ability to cause disease in guinea pigs following intratracheal inoculation. NU216R-infected animals yielded 1,000-fold fewer bacteria from their lungs and spleen compared to wild-type-130b-infected animals that had received a 50-fold-lower dose. Moreover, NU216R-infected animals subsequently cleared the bacteria from these sites. While infection with 130b resulted in high fever, weight loss, and ruffled fur, inoculation with NU216R did not elicit any signs of disease. DNA sequence analysis revealed that the transposon insertion in NU216R lies in the first open reading frame of a two-gene operon. This open reading frame (iraA) encodes a 272-amino-acid protein that shows sequence similarity to methyltransferases. The second open reading frame (iraB) encodes a 501-amino-acid protein that is highly similar to di- and tripeptide transporters from both prokaryotes and eukaryotes. Southern hybridization analyses determined that the iraAB locus was largely limited to strains of L. pneumophila, the most pathogenic of the Legionella species. A newly derived mutant containing a targeted disruption of iraB showed reduced ability to grow under iron-depleted extracellular conditions, but it did not have an infectivity defect in the macrophage-like U937 cells. These data suggest that iraA is critical for virulence of L. pneumophila while iraB is involved in a novel method of iron acquisition which may utilize iron-loaded peptides.
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PMID:The Legionella pneumophila iraAB locus is required for iron assimilation, intracellular infection, and virulence. 1067 9