Tuning of hydrophobic–hydrophilic balance for the development of a salt-tolerant and protease-resistant lipopeptide AMP.

Antimicrobial peptides show promise in combating microbial infections in the age of rapidly growing resistance against antibiotics. The salt sensitivity of their activity, protease susceptibility, and cytotoxicity are some of the disadvantages that limit the commercial success of AMPs. In this study, the hydrophobic–hydrophilic balance of lipopeptides was tuned to generate a highly potent AMP, P18, which overcomes the limitations of the existing AMPs. P18 is a non-cytotoxic, salt-tolerant, and protease-resistant AMP, with no development of resistance over 16 generations in MRSA, which is highly potent against ESKAPE pathogens such as P. aeruginosa, K. pneumoniae, S. aureus, and methicillin-resistant S. aureus (MRSA). This study explores and establishes the direct effect of the hydrophobic–hydrophilic balance of peptides on their various properties such as secondary structure, self-assembly (morphology and kinetics), antimicrobial potency (salt-tolerance, kinetics, etc.), and protease-resistance ability. Thus, peptides with tailor-made properties and functions can be designed in the future by being able to control and tune their overall hydrophobic–hydrophilic balance. [ABSTRACT FROM AUTHOR]