Enhancing the antibacterial activity of PMAP‐37 by increasing its hydrophobicity

: With increasing resistance against conventional antibiotics, there is an urgent need to discover novel substances to replace antibiotics. This need provides an opportunity for the development of antimicrobial peptides (AMPs). To develop new AMPs with effective and safe therapeutic effects, two PMAP-37 analogs called PMAP-37(R13-I) and PMAP-37(K20/27-I) were designed to increase hydrophobicity. Antimicrobial susceptibility testing and animal infection models were used to assess their antibacterial activity. The results showed that the minimal inhibitory concentrations of PMAP-37(R13-I) were lower than those of PMAP-37 for two gram-negative strains. Compared with PMAP-37, PMAP-37(K20/27-I) not only inhibited the growth of most bacterial strains, but also exhibited antibacterial activity against Shigella flexneri CICC21534. In addition, PMAP-37(K20/27-I) exhibited pH and thermal stability. PMAP-37(R13-I) had a therapeutic effect only in mice infected with Salmonella typhimurium SL1344. However, PMAP-37(K20/27-I) exhibited the therapeutic effects, whether in the clinical symptoms, the tissue lesions, or the tissue bacterial loads and the survival rates in mice infected with Staphylococcus aureus ATCC25923 or S. typhimurium SL1344. Therefore, PMAP-37(K20/27-I) can be used as a substitute for antibiotics against infection with bacterial strains.