The Antimicrobial Effects of TP4-LYC1 Fusion Protein against Multidrug-Resistant A. Baumannii

Colistin, tigecycline and ampicillin/sulbactam (high dose) are the only antibiotics with high efficacy against Acinetobacter baumannii and their last line of treatment. So, investigation of new antimicrobial agents with potential activity against these pathogens seems essential. Antimicrobial peptides are natural agents that play an important role in innate immunity against various types of pathogens. In this project, the antimicrobial activity of TP4-LYC1, an antimicrobial peptide consisting of Tilapia Piscidin 4 (TP4) with lycosin-1, was investigated against resistant A. baumannii as well as the synergistic effects of this chimeric peptide with colistin and meropenem.

Optimization the cleavage of each peptides (TP4, LYC1, and TP4-LYC1) to earn the most amounts of peptides was performed based on the incubation temperature, time of incubation and the cleavage buffer pH. Finally, the antimicrobial effects of each peptide, alone or in combination with colistin or meropenem was analyzed by broth micro-dillusion and checker board methods, respectively.

The best condition for the cleavage of TP4, was pH 6.5 for 24 Hours incubation time. These conditions for LYC1 and the chimeric peptide was concluded as pH 4 for 24 and 48 Hours incubation time, respectively. The antibacterial activity of TP4 was less than TP4-LYC1 for each biological sample. Also, TP4-LYC1 has synergistic effects with Meropenem and Colistin in most cases.

TP4-LYC1 has the potential to be used as a candidate for the treatment of infections caused by A. baumanni in combination with routine effective antibiotics in order to reduce the dosage of these antibiotics.