Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A Bordetella bronchiseptica iron transport mutant was isolated following an enrichment procedure based on streptonigrin resistance. The mutant displayed a growth defect on iron-restricted medium containing ferric alcaligin as the sole iron source. In addition to the apparent inability to acquire iron from the siderophore, the mutant failed to produce alcaligin as well as two known iron-regulated proteins, one of which is the AlcC alcaligin biosynthesis protein. A 1.6-kb KpnI-PstI Bordetella pertussis DNA fragment mapping downstream of the alcaligin biosynthesis genes alcABC restored both siderophore biosynthesis and expression of the iron-regulated proteins to the mutant. Nucleotide sequencing of this complementing 1.6-kb region identified an open reading frame predicted to encode a protein with strong similarity to members of the AraC family of transcriptional regulators, for which we propose the gene designation alcR. Primer extension analysis localized an iron-regulated transcription initiation site upstream of the alcR open reading frame and adjacent to sequences homologous to the consensus Fur repressor binding site. The AlcR protein was produced by using an Escherichia coli expression system and visualized in electrophoretic gels. In-frame alcR deletion mutants of B. pertussis and B. bronchiseptica were constructed, and the defined mutants exhibited the alcR mutant phenotype, characterized by the inability to produce and transport alcaligin and express the two iron-repressed proteins. The cloned alcR gene provided in trans restored these siderophore system activities to the mutants. Together, these results indicate that AlcR is involved in the regulation of Bordetella alcaligin biosynthesis and transport genes and is required for their full expression.
 ...
PMID:Identification and characterization of alcR, a gene encoding an AraC-like regulator of alcaligin siderophore biosynthesis and transport in Bordetella pertussis and Bordetella bronchiseptica. 947 40

A Fur titration assay was used to isolate DNA fragments bearing putative Fur binding sites (FBS) from a partial Bordetella bronchiseptica genomic DNA library. A recombinant plasmid bearing a 3.5-kb DNA insert was further studied. Successive deletions in the cloned fragment enabled us to map a putative FBS at about 2 kb from one end. Sequence analysis revealed the presence of an FBS upstream from a new gene encoding an AraC-type transcriptional regulator. The deduced protein displays similarity to PchR, an activator of pyochelin siderophore and ferripyochelin receptor synthesis in Pseudomonas aeruginosa. Homologous genes in Bordetella pertussis and Bordetella parapertussis were PCR amplified, and sequence comparisons indicated a very high conservation in the three species. The B. pertussis and B. bronchiseptica chromosomal genes were inactivated by allelic exchange. Under low-iron growth conditions, the mutants did not secrete the alcaligin siderophore and lacked AlcC, an alcaligin biosynthetic enzyme. Alcaligin production was restored after transformation with a plasmid bearing the wild-type gene. On the basis of its role in regulation of alcaligin biosynthesis, the new gene was designated alcR. Additional sequence determination showed that alcR is located about 2 kb downstream from the alcABC operon and is transcribed in the same orientation. Two tightly linked open reading frames, alcD and alcE, were identified between alcC and alcR. AlcE is a putative iron-sulfur protein; AlcD shows no homology with the proteins in the database. The production of major virulence factors and colonization in the mouse respiratory infection model are AlcR independent.
 ...
PMID:Identification of AlcR, an AraC-type regulator of alcaligin siderophore synthesis in Bordetella bronchiseptica and Bordetella pertussis. 947 41

Utilization of the enterobactin siderophore by the respiratory pathogens Bordetella pertussis and Bordetella bronchiseptica is dependent on the BfeA outer membrane receptor. This study determined that production of BfeA was increased significantly in iron-starved bacteria upon supplementation of cultures with enterobactin. A 1.01-kb open reading frame, designated bfeR, encoding a predicted positive transcriptional regulator of the AraC family was identified upstream and divergently oriented from bfeA. In iron-depleted cultures containing enterobactin, a Bordetella bfeR mutant exhibited markedly decreased BfeA receptor production compared to that of the wild-type strain. Additionally, B. pertussis and B. bronchiseptica bfeR mutants exhibited impaired growth with ferric enterobactin as the sole source of iron, demonstrating that effective enterobactin utilization is bfeR dependent. Transcriptional analysis using bfeA-lacZ reporter fusions in wild-type strains demonstrated that bfeA transcription was stimulated in iron-depleted conditions in the presence of enterobactin, compared to modest expression levels in cultures lacking enterobactin. In contrast, bfeA transcription in B. pertussis and B. bronchiseptica bfeR mutants was completely unresponsive to the enterobactin inducer. bfeA transcriptional analyses of a bfeA mutant demonstrated that induction by enterobactin did not require BfeA receptor-mediated uptake of the siderophore. These studies establish that bfeR encodes an enterobactin-dependent positive regulator of bfeA transcription in these Bordetella species.
 ...
PMID:The BfeR regulator mediates enterobactin-inducible expression of Bordetella enterobactin utilization genes. 1548 42