Phase variation of the gonococcal siderophore receptor FetA

Carson, S. D.; Stone, Bronte A.; Beucher, Margaret; Fu, Jennifer; Sparling, P. Frederick

doi:10.1046/j.1365-2958.2000.01873.x

Cited by 53 publications

(42 citation statements)

References 31 publications

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“…5A is that the frpB promoter is iron responsive in each strain tested and, furthermore, the overall amount of transcript in the complemented mutant Fko-C is significantly higher than in the other strains. However, the promoter sequence contains a tract of 11 C's between the Ϫ10 and Ϫ35 hexamers similar to the phase-variable promoter reported in the closely related N. gonorrhoeae (5). We therefore, sequenced the promoter regions in the different backgrounds and identified that indeed the length of the C tract was variable, with 10 instead of 11 C's in the Fko-C strain.…”

Section: Vol 188 2006mentioning

confidence: 68%

Effect ofNeisseria meningitidisFur Mutations on Global Control of Gene Transcription

et al. 2006

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The ferric uptake regulator Fur is a well-known iron-responsive repressor of gene transcription, which is used by many bacteria to respond to the low-iron environment that pathogens encounter during infection. In this study we used comparative transcriptome analysis to define the role of the Fur protein in the global control of gene transcription and iron regulation in Neisseria meningitidis. By using the Fur-null mutant and its complemented derivative, we identified 83 genes whose transcription is controlled by Fur. We report that Fur may control differential expression of these genes by binding directly to their promoters or through indirect mechanisms. In addition, mutation of the fur gene resulted in the induction of the heat shock response, and transcription of these genes does not respond to iron limitation. Furthermore, analysis of the iron starvation stimulon in the Fur-null mutant provided evidences of iron-responsive regulation that is independent of Fur. We began to dissect the regulatory networks of Fur and the heat shock (stress) response in N. meningitidis, and the observed interlink between the two circuits is discussed.

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Section: Vol 188 2006mentioning

confidence: 68%

Effect ofNeisseria meningitidisFur Mutations on Global Control of Gene Transcription

et al. 2006

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“…FetA, formerly FrpB, is an iron-repressed TonB-dependent receptor which binds ferric enterobactin. In gonococci, FetA expression can be down-regulated by phase variation (2). Inspection of the corresponding homopolymeric tracts within the meningococcal fetA promoter sequence of strain MC58 (15) suggests that phase variation is possible in this species also (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Deletion of the MeningococcalfetAGene Used for Antigen Sequence Typing of Invasive and Commensal Isolates from Germany: Frequencies and Mechanisms

et al. 2007

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Antigen sequence typing (ST) of FetA is part of the molecular typing scheme of Neisseria meningitidis. Among invasive meningococcal isolates from 2,201 patients in Germany, we identified 11 strains lacking the fetA gene because of deletions mediated by repeat arrays flanking the gene, i.e., Correia elements, repeat sequence 13 (RS13), and duplicated RS3. Geographic mapping and multilocus ST of invasive isolates revealed that fetA deletion was a sporadic event without genetic fixation. Among 821 carrier strains, 12 strains lacked fetA, suggesting that fetA is maintained during asymptomatic carriage. Interestingly, most of these isolates belonged to the multilocus ST-35 clonal complex (cc). ST-35 cc strains and the recently published ST-192 strains from Burkina Faso may benefit from loss of fetA, but their infrequent occurrence among invasive isolates currently does not affect fetA antigen ST.

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“…In addition to the sequence diversity of FetA, variable expression in both meningococci and gonococci (Carson et al, 2000) may also reduce the effectiveness of this protein as a vaccine component. This provides a further parallel with the PorA protein which is also phase-variable (van der Ende et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

2003

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Meningococcal FetA (FrpB), an iron-regulated outer-membrane protein and vaccine component, was shown to be highly diverse: a total of 60 fetA alleles, encoding 56 protein sequences, were identified from 107 representative Neisseria meningitidis isolates. Phylogenetic analysis established that the allelic variants had been generated by both point mutation and horizontal genetic exchange. Nucleotide substitution was unevenly distributed in the gene, which contained both conserved and variable sequence regions. The most conserved region of the translated peptide sequence corresponded to an amino-terminal domain of the protein and the most diverse region to a previously identified variable region (VR). A nomenclature system for the peptides encoded by the VR was devised which classified 24 variants into 5 FetA variant families. On the basis of these data, murine polyclonal sera specific for four FetA variants were generated. The reactivities of these sera in whole-cell ELISA experiments were consistent with the hypothesis that the VR encoded an immunodominant epitope and indicated that the sera reacted mainly with variants against which they were raised. The diversity of this protein is likely to limit its effectiveness as a vaccine component.

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Phase variation of the gonococcal siderophore receptor FetA

Cited by 53 publications

References 31 publications

Effect ofNeisseria meningitidisFur Mutations on Global Control of Gene Transcription

Effect ofNeisseria meningitidisFur Mutations on Global Control of Gene Transcription

Deletion of the MeningococcalfetAGene Used for Antigen Sequence Typing of Invasive and Commensal Isolates from Germany: Frequencies and Mechanisms

Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

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