Effects of Ceragenins and Antimicrobial Peptides on the A549 Cell Line and an In Vitro Co-Culture Model of A549 Cells and Pseudomonas aeruginosa

Pseudomonas aeruginosa is an important pathogen that can adhere to host tissues and epithelial surfaces, especially during chronic infections such as cystic fibrosis (CF) lung infections. The effect of ceragenins and antimicrobial peptides (AMP) on this colonization was investigated in a co-culture infection model. After determining the antimicrobial effects of the substances on P. aeruginosa planktonic cells, their cytotoxicity on the A549 cell line was also determined. After the A549 cell line was infected with P. aeruginosa, the effect of antimicrobials on intracellular bacteria as well as the effects in inhibiting the adhesion of P. aeruginosa were investigated. In addition, LDH release from cells was determined by performing an LDH experiment to understand the cytotoxicity of bacterial infection and antimicrobial treatment on cells. CSA-131 was determined as the antimicrobial agent with the highest antimicrobial activity, while the antimicrobial effects of AMPs were found to be much lower than those of ceragenins. The antimicrobial with the lowest IC(50) value was determined as the combination of CSA-131 with Pluronic F127. CSA-13 has been determined to be the most effective antimicrobial with its effectiveness to both intracellular bacteria and bacterial adhesion. Nevertheless, further safety, efficacy, toxicity, and pharmacological studies of ceragenins are needed to evaluate clinical utility.