LetterOfIntent_Shannon

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More than 50% of our infectious diseases are caused by commensal bacterial species such as

Staphylococcus aureus and Pseudomonas aeruginosa naturally living in our bodies (Costerton et al., 1999). We intend to study Pseudomonas aeruginosa because it is a ubiquitous, opportunistic, infectious bacterium that causes devastating chronic infections in immunocompromised eukaryotic organisms, contributes to cystic fibrosis progression, and produces biofilms that are not easily eradicated by conventional antibiotic therapy (Costerton et al., 1999).

Pseudomonas aeruginosa is a gram-negative bacillus known to carry N-acyl-homoserine lactone

(AHL) signal molecules on its cell membrane surface to activate biofilm formation, sense its population density, and control its virulence arsenal time of discharge through quorum sensing communication (Bjarnsholt and Givskov, 2007). Once a biofilm has formed, Pseudomonas aeruginosa releases massive quantities of lipopolysaccharides, exoenzyme S, and alginate virulence factors simultaneously to overwhelm the host’s immune system (Bjarnsholt and

Givskov, 2007). In defense, antibodies are produced by the host, but these antibodies are ineffective because they cannot penetrate the biofilm’s thick protective layer consisting of an extracellular polysaccharide matrix (Costerton et al., 1999). Thus, an agent capable of blocking the quorum sensing pathway; or, an agent capable of carrying an antibiotic or toxin to a

Pseudomonas aeruginosa bacterial cell and deliver this toxin intracellularly is required to eliminate a chronic Pseudomonas aeruginosa infection (Bjarnsholt and Givskov, 2007).

We will develop a method using copper-oxide nanoparticles to target a biofilm produced by

Pseudomonas aeruginosa and deliver an agent, antibody or toxin across the biofilm’s protective layer to eradicate the bacterial cells residing inside the biofilm. Thus, our research question is:

Can copper-oxide nanoparticles carry agents, antibodies or toxins across the biofilm’s protective layer created by Pseudomonas aeruginosa ?

Describe the method or plan:

Mark, if you use this research article to describe the method: Iron and Pseudomonas aeruginosa biofilm formation by Banin, I have the reference on the next page with my two references.

REFERENCES

Banin E, Vasil ML, Greenberg EP. 2005. Iron and Pseudomonas aeruginosa biofilm formation.

Proceedings of the National Academy of Sciences of the United States of America

[Internet]. [cited 2011 Feb 5]; 102(31):11076-81. Available from : http://www.jstor.org.ezproxy.lib.ucalgary.ca/stable/pdfplus/3376219.pdf.

Bjarnsholdt T, Givskov M. 2007. Quorum-sensing blockade as a strategy for enhancing host defences against bacterial pathogens. Philosophical Transactions: Biological Sciences

[Internet]. [cited 2011 Feb 5]; 362(1483):1213-22. Available from : http://www.jstor.org.ezproxy.lib.ucalgary.ca/stable/pdfplus/20209928.pdf.

Costerton JW, Stewart PS, Greenberg EP. 1999. Bacterial biofilms: A common cause of persistent infections. Science [Internet]. [cited 2011 Feb 5]; 284(1518):1318-22.

Available from : http://www.jstor.org.ezproxy.lib.ucalgary.ca/stable/pdfplus/20209928.pdf

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