Identification of novel anti-pathogenic compounds against pseudomonas aeruginosa through drug repurposing
Tan, Casandra Ai Zhu
Date of Issue2017-04-26
School of Biological Sciences
Biofilm formations have cause undesirable consequences because they are less susceptible to antimicrobial treatments and are protected from host immune responses. Despite this, pharmaceutical industry has produced very few novel antibiotics. Thus, there is a need for development of new drugs to eradicate biofilms. A promising approach is to repurpose drugs originally produced for other purposes for anti-pathogenic activity, as it circumvents the high cost and time associated with traditional de novo drug discovery. The aim of this study was to repurpose drugs from a library of 1,600 compounds as anti-pathogenic drugs against Pseudomonas aeruginosa via microtiter plate-based biofilm formation assay. Nisoldipine, a calcium channel blocker, was confirmed as a potential quorum sensing inhibitor because it showed inhibition of lasB expression in Pseudomonas aeruginosa (IC50 = 69.31 M) when screened against quorum sensing reporter strains. Nisoldipine also affected various virulence factors, including slight reduction in elastase activity, 20% increase in rhamnolipid production, 7% increase in swarming motility and inhibition of biofilm formation upon combinatory treatment with antibiotics. This is the first documentation indicating nisoldipine with some anti-pathogenic activities. Although results achieved suggested that nisoldipine might not be a promising compound, drug repurposing persists as a strategic approach for drug development against biofilms.
Final Year Project (FYP)
Nanyang Technological University