(197b) A New Antimicrobial Peptide-Antibiotic Combination Strategy for P. Aeruginosa Inactivation

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen which causes several types of severe infections in humans. Traditional antibiotic treatments are not always effective at curing these infections because the lower outer membrane permeability of P. aeruginosa limits the uptake of antibiotics. In addition, many bacteria are now resistant to the commonly used antibiotics for P. aeruginosa infections. Currently, antibiotic combinations are administered to treat P. aeruginosa infections, such as Ceftolozane-Tazobactam or Ceftazidime-Avibactam in combination. However, there are concerns that the antibiotic combination may accelerate the already existing drug resistance. We propose developing a novel treatment strategy through combining the human antimicrobial peptide LL-37 with different antibiotics, to combat P. aeruginosa strains in vitro. Preliminary results showed that LL-37 exhibits synergistic effects against P. aeruginosa when combined with some traditional antibiotics. Further, the effective concentrations of LL-37 and antibiotics decrease substantially compared with the original minimum inhibitive concentrations, suggesting that there is the potential to decrease the cytotoxicity during treatment. In addition, some antibiotics we used in our research are not considered as options to treat infections in clinical due to their weak penetration abilities to the outer membrane of P. aeruginosa. It is therefore promising that they were effective in the combination strategy. We infer that LL-37 helped to increase the outer membrane permeability of P. aeruginosa and thus enhance the uptake of antibiotics, which makes these antibiotics effective against P. aeruginosa. Further research will be conducted to help elucidate the mechanism of these synergistic effects.