Effects of ceragenins and antimicrobial peptides on pseudomonas aeruginosa biofilm formed on human airway epithelial cell

Pseudomonas aeruginosa is an important pathogen that can form biofilms in host tissues and epithelial surfaces, especially during chronic infections such as cystic fibrosis (CF) lung. Long-term colonization of P. aeruginosa in the lungs is the primary cause of mortality and morbidity in people with CF with abnormal airway epithelium. Antimicrobial peptides (AMP) and ceragenins, which act through the same antimicrobial mechanisms as AMPs and designed as synthetic derivatives of AMPs, are the new generation antimicrobial molecules. The effects of ceragenins and AMP were investigated in a co-culture infection model. In this study, CSA-13, CSA-44, CSA-90, CSA-131, CSA-131-poloxamer (CSA-131P), CSA-138, CSA-142, CSA-144 and CSA-192 as ceragenins and, cecropin, magainin and LL-37 as AMPs were used. After determining the antimicrobial effects of the substances on P. aeruginosa planktonic cells, their cytotoxicity on the A549 cell line was also determined by MTT test. After A549 cell line was infected with P. aeruginosa, the effect of antimicrobials on intracellular bacteria as well as the effects in inhibiting adhesion and biofilm formation of P. aeruginosa were investigated. In addition, Lactate dehydrogenase (LDH) release from cells was determined by performing an LDH experiment to understand the cytotoxicity of bacterial infection and antimicrobial treatment on cells. According to the Minimum Inhibitory Concentration (MIC) results, 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 that of ceragenins. The ceragenin with the lowest IC50 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 biofilm formation. Further studies should be continued by making various combinations of CSA-13 in order to reduce its cytotoxicity.