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Egon Ozer


egonozer@gmail.com
Mentor: Joseph Zabner, M.D.
Lab Phone: 335-8457

Prevention of chronic bacterial infection in lungs by interrupting the bacterial quorum sensing system

Pseudomonas aeruginosa infection in the lungs of cystic fibrosis (CF) patients remains a major cause of morbidity and mortality in this population. Pseudomonas bacteria are able to form biofilms in the airways via a quorum sensing pathway. Two types of quorum sensing molecules, also called autoinducers, are secreted and detected by Pseudomonas aeruginosa: N-butanoyl-L-homoserine lactone (C4-HSL) and N-(3-oxododecanoyl)-L-homoserine lactone (3OC12-HSL). It is thought that degradation of these autoinducers in the lungs of CF patients will block the quorum sensing pathway and prevent or reverse the formation of Pseudomonas biofilms. To this end, we are exploring several avenues of research. The autoinducer inhibitor genes, aiiA, aiiB, andaiiD, have been isolated from various strains of bacteria and function by enzymatically hydrolyzing the lactone ring of autoinducers or cleaving the acyl side-chain. Transfecting human cell cultures with aiiA or aiiB has revealed synthesis of a full length transcript by RT-PCR for both genes. The translation profile and functional status of aiiA and aiiB from human cells is currently being examined. We are also looking into the innate ability of some cell lines to inactivate autoinducer. This phenomenon is being explored by structural studies of inactivated autoinducer to determine the mechanism by which cells can block autoinducer signals as well as comparison of gene expression profiles between cell lines that are able to inactivate quorum sensing signals versus those that are not. Finally, in pursuit of more efficient gene delivery to human airways in preparation for eventual gene therapy approaches to quorum sensing interruption, we are examining the use of platelet-derived growth factor receptor (PDGFR) by adeno-associated virus (AAV) for entry into airway epithelia.

Abstracts:

Ozer EA, and Zabner J. Inactivation of a bacterial quorum-sensing signal by expression of bacterial autoinducer inhibitor, aiiA, in mammalian cells. American Society for Gene Therapy, Abstract #566. June 4, 2004.

Publications:

Stoltz DA, Ozer EA, Taft PJ, Barry M, Liu L, Kiss PJ, Moninger TO, Parsek MR, Zabner J. Drosophila are protected from Pseudomonas aeruginosa lethality by transgenic expression of paraoxonase-1. J Clin Invest. 2008 Sep;118(9):3123-31. PubMed PMID: 18704198; PubMed Central PMCID: PMC2515384.

Stoltz DA, Ozer EA, Ng CJ, Yu JM, Reddy ST, Lusis AJ, Bourquard N, Parsek MR, Zabner J, Shih DM. Paraoxonase-2 deficiency enhances Pseudomonas aeruginosa quorum sensing in murine tracheal epithelia. Am J Physiol Lung Cell Mol Physiol. 2007 Apr;292(4):L852-60. Epub 2006 Nov 22. PubMed PMID: 17122353.

Ozer EA, Pezzulo A, Shih DM, Chun C, Furlong C, Lusis AJ, Greenberg EP, Zabner J. Human and murine paraoxonase 1 are host modulators of Pseudomonas aeruginosa quorum-sensing. FEMS Microbiol Lett. 2005 Dec 1;253(1):29-37. Epub 2005 Oct 5. PubMed PMID: 16260097.

Brown CL, Graham SM, Cable BB, Ozer EA, Taft PJ, Zabner J. Xylitol enhances bacterial killing in the rabbit maxillary sinus. Laryngoscope. 2004 Nov;114(11):2021-4. PubMed PMID: 15510034.

Chun CK, Ozer EA, Welsh MJ, Zabner J, Greenberg EP. Inactivation of a Pseudomonas aeruginosa quorum-sensing signal by human airway epithelia. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3587-90. Epub 2004 Feb 17. PubMed PMID: 14970327; PubMed Central PMCID: PMC373506.



Honors and Awards

  • Iowa Orthopedic Society Medical Student Research Award, Carver College of Medicine. Internal Medici
  • American Society for Cell Biology
  • American Society for Cell Biology National Meeting, San Francisco, 2003.