Pyoverdine, the Major Siderophore in Pseudomonas aeruginosa, Evades NGAL Recognition
Pseudomonas aeruginosa is the most common pathogen that persists in the cystic fibrosis lungs. Bacteria such as P. aeruginosa secrete siderophores (iron-chelating molecules) and the host limits bacterial growth by producing neutrophil-gelatinase-associated lipocalin (NGAL) that specifically scavenge...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Interdisciplinary Perspectives on Infectious Diseases |
| Online Access: | http://dx.doi.org/10.1155/2012/843509 |
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| author | Mary E. Peek Abhinav Bhatnagar Nael A. McCarty Susu M. Zughaier |
| author_facet | Mary E. Peek Abhinav Bhatnagar Nael A. McCarty Susu M. Zughaier |
| author_sort | Mary E. Peek |
| collection | DOAJ |
| description | Pseudomonas aeruginosa is the most common pathogen that persists in the cystic fibrosis lungs. Bacteria such as P. aeruginosa secrete siderophores (iron-chelating molecules) and the host limits bacterial growth by producing neutrophil-gelatinase-associated lipocalin (NGAL) that specifically scavenges bacterial siderophores, therefore preventing bacteria from establishing infection. P. aeruginosa produces a major siderophore known as pyoverdine, found to be important for bacterial virulence and biofilm development. We report that pyoverdine did not bind to NGAL, as measured by tryptophan fluorescence quenching, while enterobactin bound to NGAL effectively causing a strong response. The experimental data indicate that pyoverdine evades NGAL recognition. We then employed a molecular modeling approach to simulate the binding of pyoverdine to human NGAL using NGAL’s published crystal structures. The docking of pyoverdine to NGAL predicted nine different docking positions; however, neither apo- nor ferric forms of pyoverdine docked into the ligand-binding site in the calyx of NGAL where siderophores are known to bind. The molecular modeling results offer structural support that pyoverdine does not bind to NGAL, confirming the results obtained in the tryptophan quenching assay. The data suggest that pyoverdine is a stealth siderophore that evades NGAL recognition allowing P. aeruginosa to establish chronic infections in CF lungs. |
| format | Article |
| id | doaj-art-30fbef029c734e45a7d80cdabbc35d34 |
| institution | Kabale University |
| issn | 1687-708X 1687-7098 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Interdisciplinary Perspectives on Infectious Diseases |
| spelling | doaj-art-30fbef029c734e45a7d80cdabbc35d342025-02-03T01:12:30ZengWileyInterdisciplinary Perspectives on Infectious Diseases1687-708X1687-70982012-01-01201210.1155/2012/843509843509Pyoverdine, the Major Siderophore in Pseudomonas aeruginosa, Evades NGAL RecognitionMary E. Peek0Abhinav Bhatnagar1Nael A. McCarty2Susu M. Zughaier3School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USASchool of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USADivision of Pulmonology, Allergy/Immunology, Cystic Fibrosis, and Sleep, Department of Pediatrics and Emory+Children’s Center for Cystic Fibrosis Research, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, GA 30322, USADivision of Pulmonology, Allergy/Immunology, Cystic Fibrosis, and Sleep, Department of Pediatrics and Emory+Children’s Center for Cystic Fibrosis Research, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, GA 30322, USAPseudomonas aeruginosa is the most common pathogen that persists in the cystic fibrosis lungs. Bacteria such as P. aeruginosa secrete siderophores (iron-chelating molecules) and the host limits bacterial growth by producing neutrophil-gelatinase-associated lipocalin (NGAL) that specifically scavenges bacterial siderophores, therefore preventing bacteria from establishing infection. P. aeruginosa produces a major siderophore known as pyoverdine, found to be important for bacterial virulence and biofilm development. We report that pyoverdine did not bind to NGAL, as measured by tryptophan fluorescence quenching, while enterobactin bound to NGAL effectively causing a strong response. The experimental data indicate that pyoverdine evades NGAL recognition. We then employed a molecular modeling approach to simulate the binding of pyoverdine to human NGAL using NGAL’s published crystal structures. The docking of pyoverdine to NGAL predicted nine different docking positions; however, neither apo- nor ferric forms of pyoverdine docked into the ligand-binding site in the calyx of NGAL where siderophores are known to bind. The molecular modeling results offer structural support that pyoverdine does not bind to NGAL, confirming the results obtained in the tryptophan quenching assay. The data suggest that pyoverdine is a stealth siderophore that evades NGAL recognition allowing P. aeruginosa to establish chronic infections in CF lungs.http://dx.doi.org/10.1155/2012/843509 |
| spellingShingle | Mary E. Peek Abhinav Bhatnagar Nael A. McCarty Susu M. Zughaier Pyoverdine, the Major Siderophore in Pseudomonas aeruginosa, Evades NGAL Recognition Interdisciplinary Perspectives on Infectious Diseases |
| title | Pyoverdine, the Major Siderophore in Pseudomonas aeruginosa, Evades NGAL Recognition |
| title_full | Pyoverdine, the Major Siderophore in Pseudomonas aeruginosa, Evades NGAL Recognition |
| title_fullStr | Pyoverdine, the Major Siderophore in Pseudomonas aeruginosa, Evades NGAL Recognition |
| title_full_unstemmed | Pyoverdine, the Major Siderophore in Pseudomonas aeruginosa, Evades NGAL Recognition |
| title_short | Pyoverdine, the Major Siderophore in Pseudomonas aeruginosa, Evades NGAL Recognition |
| title_sort | pyoverdine the major siderophore in pseudomonas aeruginosa evades ngal recognition |
| url | http://dx.doi.org/10.1155/2012/843509 |
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