Development of Topical Treatment for Pseudomonas aeruginosa Wound Infections by Quorum-Sensing Inhibitors Mediated by Poly(amidoamine) (PAMAM) Dendrimers
Annual rept. 15 Dec 2011-14 Dec 2012
MEDICAL COLL OF SOUTH CAROLINA CHARLESTON
Pagination or Media Count:
During this performance period, we have made significant progress on the following Tasks as stated in SOW 1, 2, 4, 5, 6, 7 and 8. For Specific Aim 1, we have synthesized 18 QSI-PAMAM complexes by encapsulation Task 1, conjugation Task 2, or both. For Specific Aim 2, we have established all the protocols to measure planktonic and biofilm growth of PA Task 5, turnover of PAMAM in PA Task 6, quinolone signals by HPLC-MS Task 7, and extracellular virulence factors Task 8. The most significant finding was the specific inhibition of PAMAM dendrimers on Pseudomonas aeruginosa PA biofilm formation and growth. This is significant because PA in the biofilm form is known to be up to 1000 fold more resistant antibiotic treatments. We systematically analyzed the effects of surface charge and particle size on PA biofilm. PAMAM dendrimers with more positive charges on the surface and bigger particle sizes exhibited more potent inhibition. Confocal fluorescent microscopy showed that PAMAM dendrimers also altered the morphology of PA biofilm. In addition, combination of PAMAM dendrimers also significantly enhanced the inhibition of PA biofilm growth by antibiotic such as amikacin.
- Medicine and Medical Research