NMR solution structure of the receptor binding domain of <i>Pseudomonas aeruginosa</i> pilin strain P1. Identification of a β‐turn

Ap, Campbell; Sheth, H. B.; Rs, Hodges; Bd, Sykes

doi:10.1111/j.1399-3011.1996.tb00873.x

Cited by 13 publications

(2 citation statements)

References 67 publications

(27 reference statements)

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“…In addition to cyclization, the RBD peptides are known to be well‐structured in solution. NMR studies of PAK, PAO, KB7 and P1 peptides demonstrated the formation of two β‐turns (8,21). In contrast, many protein epitopes, when made as peptides, adopt random coil conformations.…”

Section: Discussionmentioning

confidence: 99%

Advantages of a Synthetic Peptide Immunogen Over a Protein Immunogen in the Development of an Anti‐Pilus Vaccine for Pseudomonas aeruginosa

Kao

Hodges²

2009

Chem Biol Drug Des

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The type IV pilus is an important adhesin in the establishment of infection by Pseudomonas aeruginosa. We have previously reported on a synthetic peptide vaccine targeting the receptor-binding domain of the main structural subunit of the pilus, PilA. The receptor-binding domain is a 14-residue disulfide loop at the C-terminal end of the pilin protein. The objective of this study was to compare the immunogenicity of a peptide-conjugate to a protein subunit immunogen to determine which was superior for use in an anti-pilus vaccine. BALB/c mice were immunized with the native PAK strain pilin protein and a synthetic peptide of the receptor-binding domain conjugated to keyhole limpet haemocyanin. A novel pilin protein with a scrambled receptor-binding domain was used to characterize receptor-binding domain-specific antibodies. The titres against the native pilin of the animals immunized with the synthetic peptide-conjugate were higher than the titres of animals immunized with the pilin protein. In addition, the affinities of anti-peptide sera for the intact pilin receptor-binding domain were significantly higher than affinities of anti-pilin protein sera. These results have significant implications for vaccine design and show that there are significant advantages in using a synthetic peptide-conjugate over a subunit pilin protein for an anti-pilus vaccine.

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Section: Discussionmentioning

confidence: 99%

Advantages of a Synthetic Peptide Immunogen Over a Protein Immunogen in the Development of an Anti‐Pilus Vaccine for Pseudomonas aeruginosa

Kao

Hodges²

2009

Chem Biol Drug Des

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“…The 14-residue loops, which comprise residues 129-142, consist of two Cys residues at positions 129 and 142, conserved or semiconserved residues at positions 131, 134, 137, and 139-141 and variable residues at positions 130, 132, 133, 135, 136, and 138 (Fig. 1 NMR solution structures of 17 residue peptides of PAK, 25 PAO and KB7 7 pilin (128-144) and a 23-residue peptide from P1 pilin (126-148) 8 showed that all these peptides possessed consecutive type-I and type-II β-turns. The N-terminus of the pilin protein monomer (residues 1-28) is responsible for oligomerization.…”

Section: Figurementioning

confidence: 99%

Antiadhesin Peptide-Based Vaccines for Pseudomonas aeruginosa

Hartsock¹,

Hackbarth²,

Hodges³

2013

Handbook of Biologically Active Peptides

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Synthetic peptide vaccine and antibody therapeutic development: Prevention and treatment of Pseudomonas aeruginosa

Cachia

Hodges

2003

Biopolymers

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Pseudomonas aeruginosa and Pseudomonas maltophilia account for 80% of opportunistic infections by pseudomonads. Pseudomonas aeruginosa is an opportunistic pathogen that causes urinary tract infections, respiratory system infections, dermatitis, soft tissue infections, bacteremia, and a variety of systemic infections, particularly in patients with severe burns, and in cancer and AIDS patients who are immunosuppressed. Pseudomonas aeruginosa is notable for its resistance to antibiotics, and is therefore a particularly dangerous pathogen. Only a few antibiotics are effective against Pseudomonas, including fluoroquinolones, gentamicin, and imipenem, and even these antibiotics are not effective against all strains. The difficulty treating Pseudomonas infections with antibiotics is most dramatically illustrated in cystic fibrosis patients, virtually all of whom eventually become infected with a strain that is so resistant that it cannot be treated. Since antibiotic therapy has proved so ineffective as a treatment, we embarked on a research program to investigate the development of a synthetic peptide consensus sequence vaccine for this pathogen. In this review article we will describe our work over the last 15 years to develop a synthetic peptide consensus sequence anti-adhesin vaccine and a related therapeutic monoclonal antibody (cross-reactive to multiple strains) to be used in the prevention and treatment of P. aeruginosa infections. Further, we describe the identification and isolation of a small peptide structural element found in P. aeruginosa strain K (PAK) bacterial pili, which has been proven to function as a host epithelial cell-surface receptor binding domain. Heterologous peptides are found in the pili of all strains of P. aeruginosa that have been sequenced to date. Several of these peptide sequences have been used in the development of an consensus sequence anti-adhesin vaccine targeted at the prevention of host cell attachment and further for the generation of a monoclonal antibody capable of prevention and treatment of existing infections.

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NMR solution structure of the receptor binding domain of Pseudomonas aeruginosa pilin strain P1. Identification of a β‐turn

Cited by 13 publications

References 67 publications

Advantages of a Synthetic Peptide Immunogen Over a Protein Immunogen in the Development of an Anti‐Pilus Vaccine for Pseudomonas aeruginosa

Advantages of a Synthetic Peptide Immunogen Over a Protein Immunogen in the Development of an Anti‐Pilus Vaccine for Pseudomonas aeruginosa

Antiadhesin Peptide-Based Vaccines for Pseudomonas aeruginosa

Synthetic peptide vaccine and antibody therapeutic development: Prevention and treatment of Pseudomonas aeruginosa

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