Genetic characterization of <i>Bordetella pertussis</i> filamentous haemagglutinin: a protein processed from an unusually large precursor

Domenighini, M; Relman, David A.; Capiau, Carine; Falkow, Stanley; Prugnola, Anna; Scarlato, Vincenzo; Rappuoli, Rino

doi:10.1111/j.1365-2958.1990.tb00649.x

Cited by 110 publications

(85 citation statements)

References 47 publications

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“…5). Both PfhB1 and PfhB2 contain domains with strong homology to the filamentous hemagglutinin (FhaB) of B. pertussis (19)(20)(21). FhaB governs the adherence of B. pertussis to host cells and is a major component of the acellular vaccines used to protect humans against whooping cough (22).…”

Section: Resultsmentioning

confidence: 99%

Complete genomic sequence of Pasteurella multocida ,Pm70

May

Zhang

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

313

229

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We present here the complete genome sequence of a common avian clone of Pasteurella multocida, Pm70. The genome of Pm70 is a single circular chromosome 2,257,487 base pairs in length and contains 2,014 predicted coding regions, 6 ribosomal RNA operons, and 57 tRNAs. Genome-scale evolutionary analyses based on pairwise comparisons of 1,197 orthologous sequences between P. multocida, Haemophilus influenzae, and Escherichia coli suggest that P. multocida and H. influenzae diverged Ϸ270 million years ago and the ␥ subdivision of the proteobacteria radiated about 680 million years ago. Two previously undescribed open reading frames, accounting for Ϸ1% of the genome, encode large proteins with homology to the virulence-associated filamentous hemagglutinin of Bordetella pertussis. Consistent with the critical role of iron in the survival of many microbial pathogens, in silico and wholegenome microarray analyses identified more than 50 Pm70 genes with a potential role in iron acquisition and metabolism. Overall, the complete genomic sequence and preliminary functional analyses provide a foundation for future research into the mechanisms of pathogenesis and host specificity of this important multispecies pathogen.I t has been more than a century since Louis Pasteur conducted experiments with Pasteurella multocida (Pm), first demonstrating that laboratory attenuated bacteria could be used for the development of vaccines (1). Despite this seminal discovery, the molecular mechanisms for infection and virulence of Pm have remained largely undetermined, and this organism has continued to cause a wide range of diseases in animals and humans. It is the causative agent of fowl cholera in domesticated and wild birds, hemorrhagic septicemia in cattle, atrophic rhinitis in swine, and is the most common source of infection in humans because of dog and cat bites (2, 3).Because the genomic DNA sequence encodes all of the heritable information responsible for microbial replication, virulence, host specificity, and ability to evade the immune system, a comprehensive knowledge of a pathogen's genome provides all of the necessary information required for cost-effective and targeted research into disease prevention and treatment. To better understand the molecular basis for Pm's virulence, pathogenicity, and host specificity, we sequenced the genome of a common avian isolate recovered from a recent case of fowl cholera in chickens. The analysis identified a total of 2,014 open reading frames, including several encoding putative virulence factors. In particular, Pm has two genes with significant homology to the filamentous hemagglutinin gene in Bordetella pertussis, as well as more than 50 genes with a potential role in iron uptake and metabolism. The analysis also provides strong evidence that Pm and its close relative, Hemophilus influenzae (Hi), diverged Ϸ270 million years ago (mya) and that the ␥ subdivision of the proteobacteria, a group that contains many of the pathogenic Gram-negative organisms, radiated Ϸ680 mya. Materials and Meth...

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Section: Resultsmentioning

confidence: 99%

Complete genomic sequence of Pasteurella multocida ,Pm70

May

Zhang

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

313

229

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“…of Haemophilus in¯uenzae 25,26 . PA2462 is adjacent to an ORF (PA2461) with strikingly abnormal codon usage and a G+C content of only 38.5%.…”

Section: Annotation Of P Aeruginosa Genesmentioning

confidence: 99%

Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen

Stover

Pham

Erwin

et al. 2000

Nature

3,959

2,852

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“…The FHA͞FhaC system has served as a prototype for the definition of the TPS pathway (2). FHA is synthesized as a 370-kDa precursor and processed to yield a 230-kDa mature protein by the removal of a large C-terminal fragment of unknown function (9)(10)(11). Distinct binding determinants have been identified in mature FHA (12), including a heparin-binding domain, an arginine-glycineaspartate motif and a carbohydrate recognition domain.…”

mentioning

confidence: 99%

The crystal structure of filamentous hemagglutinin secretion domain and its implications for the two-partner secretion pathway

Clantin

Hodak

Willery

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

150

184

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Filamentous hemagglutinin (FHA), the major 230-kDa adhesin of the whooping cough agent Bordetella pertussis, is one of the most efficiently secreted proteins in Gram-negative bacteria. FHA is secreted by means of the two-partner secretion (TPS) pathway. Several important human, animal, and plant pathogens also secrete adhesins and other virulence factors by using this mode of secretion. A TPS system is composed of two separate proteins, with TpsA the secreted protein and TpsB its associated specific outermembrane transporter. All TPS-secreted proteins contain a distinctive N-proximal module essential for secretion, the TPS domain. We report here the 1.7-Å structure of a functionally secreted 30-kDa N-terminal fragment of FHA. It reveals that the TPS domain folds into a ␤-helix, with three extrahelical motifs, a ␤-hairpin, a fourstranded ␤-sheet, and an N-terminal capping, mostly formed by the nonconserved regions of the TPS domain. The structure thus explains why the TPS domain is able to initiate folding of the ␤-helical motifs that form the central domain of the adhesin, because it is itself a ␤-helical scaffold. It also contains less conserved extrahelical regions most likely involved in specific properties, such as the recognition of the outer-membrane transporter. This structure is representative of the TPS domains found so far in >100 secreted proteins from pathogenic bacteria. It also provides a mechanistic insight into how protein folding may be linked to secretion in the TPS pathway.

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Genetic characterization of Bordetella pertussis filamentous haemagglutinin: a protein processed from an unusually large precursor

Cited by 110 publications

References 47 publications

Complete genomic sequence of Pasteurella multocida ,Pm70

Complete genomic sequence of Pasteurella multocida ,Pm70

Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen

The crystal structure of filamentous hemagglutinin secretion domain and its implications for the two-partner secretion pathway

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