Development of Topical Treatment for Pseudomonas aeruginosa Wound Infections by Quorum-Sensing Inhibitors Mediated by Poly(amidoamine) (PAMAM) Dendrimers.

摘要

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.