Structural Genomics: Determining the Structure of Proteins from the Infectious Agent Pseudomonas aeruginosa.
EMSL Project ID
7798
Abstract
The antibiotic resistance of Pseudomonas aeruginosa in chronic infections of the lungs of Cystic Fibrosis (CF) patients remains an important health issue to more than 30,000 children and adults in the Unites States and more than 70,000 people world wide. Many key virulence factors have been identified in P. aeruginosa, and the three-dimensional structure and function of many of the factors are known. Still, there is no effective treatment against P. aeruginosa infection in the CF lung and chronic P. aeruginosa infection remains a leading cause of morbidity and mortality in CF patients. The antibiotic resistance of P. aeruginosa stems from two primary characteristics: 1) encapsulation of the colonized bacteria in a mucoidy biofilm that challenges penetration and delivery of antibiotics across the biofilm boundary and 2) multiple, specific antibiotic mechanisms that inactivate antibiotics that reach the pathogen cells. Thus, a two-pronged research approach is needed to advance the fight against this opportunistic and deadly pathogen: 1) deeper research into the factors that regulate biofilm function and 2) research on emerging and new virulence factors that are continually being identified by new genome scale technologies. Thus, the first line of defense against this pathogen must be disruption of biofilm function, followed by an overwhelming regimen of antibiotics that can be effective once they reach the pathogen cells. Recent discoveries on how quorum sensing regulates biofilm function and how this relates to the mechanism of antibiotic resistance in P. aeruginosa are providing hope for new and effective therapeutic and prophylactic treatments. However, basic research is needed to advance our understanding of the molecular basis for quorum sensing regulation of biofilm function and how it relates to antibiotic resistance. Our focus is on determining the three-dimensional structures for three distinct groups of P. aruginosa proteins: 1) uncharacterized essential virulence factors, 2) proteins in the non-mevaonate pathway for isoprenoid synthesis, and 3) new and uncharacterized proteins implicated in the quorum sensing regulon in P. aeruginosa.
Project Details
Project type
Capability Research
Start Date
2004-12-29
End Date
2005-10-03
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Whiteaker JR, H Zhang, JK Eng, R Fang, BD Piening, L Feng, TD lorentzen, RM Schoenherr, JF Keane, T Holzman, M Fitzgibbon, C Lin, K Cooke, T Liu, DG Camp, LN Anderson, J Watts, RD Smith, M McIntosh, and AG Paulovich. 2007. "Head-to-Head Comparison of Serum Fractionation Techniques." Journal of Proteome Research 6(2):828-836.