Enhancing the antibacterial activity of antimicrobial peptide PMAP-37(F34-R) by cholesterol modification

Abstract

Background The problem of increasing resistance against conventional antibiotics has drawn people’s attention. Therefore, the development of novel antibacterial agents with effective and safe therapeutic effects is imminent. Antimicrobial peptides (AMPs) are considered a promising class of antibacterial agents due to their broad antibacterial spectrum. Results In this study, on the basis of our previously studied peptide PMAP-37(F34-R), a novel antimicrobial peptide Chol-37(F34-R) was developed by N-terminal cholesterol modification to increase hydrophobicity. We observed that the N-terminal cholesterol-modified Chol-37(F34-R) showed higher antimicrobial activity than PMAP-37(F34-R) in vitro. Chol-37(F34-R) also exhibited effective anti-biofilm activity and may kill bacteria by improving the permeability of their membranes. Chol-37(F34-R) exerted high stability in different pH, salt, serum, and boiling water environments. Chol-37(F34-R) also showed no hemolytic activity and substantially low toxicity. Furthermore, Chol-37(F34-R) exhibited good potency of bacteria eradication and promoted wound healing and abscess reduction in infected mice. Meanwhile, in S. aureus ATCC25923-infected peritonitis model, Chol-37(F34-R) exhibited an impressive therapeutic effect by reducing the decrease in systemic bacterial burden and alleviating organ damage. Conclusions Our findings suggested that the N-terminal cholesterol modification of PMAP-37(F34-R) could improve antibacterial activity. Chol-37(F34-R) displayed excellent bactericidal efficacy and impressive therapeutic effect in vivo. Thus, Chol-37(F34-R) may be a candidate for antimicrobial agents against microbial infection in the clinic.

A Thermostable, Modified Cathelicidin-Derived Peptide With Enhanced Membrane-Active Activity Against Salmonella enterica serovar Typhimurium

“…A previous study demonstrated that pre-incubated PMAP-37(F34-R) in extreme pHs exhibited a stable and maintained antibacterial activity at pH 2-8 and pH 9-11 against S. aureus ATCC 25923 and P. aeruginosa GIM1.551 ( Chen et al, 2020 ). Our results showed that P7 tolerated over a wide range of acidic, neutral even alkaline environment.…”

“…To determine pH stability, the pH of the peptide’s solution was adjusted to 3, 5, 7, 9, and 11 using 1 M NaOH or 1 M acetic acid (CH 3 COOH). P7 were incubated in the different pH conditions for 1 h, then transferred to inoculated MHB for antibacterial testing ( Chen et al, 2020 ), There was no change of the pH following the addition of peptide. To determine the sensitivity of peptide to proteolytic enzymes, the residual activity of P7 was measured after incubation the peptide with 1 mg/ml (final concentration) of proteolytic enzymes (pepsin or trypsin) at 37°C for 1 h and heat denaturation at 80°C for 1 h. To study thermostability, peptides were pre-incubated without bacteria at various temperatures (40, 60, 80, and 100°C) for 1 h and left to cool for 30 min before testing.…”

“…antibacterial activity at pH 2-8 and pH 9-11 against S. aureus ATCC 25923 and P. aeruginosa GIM1.551 (Chen et al, 2020).…”

Porcine Myeloid Antimicrobial Peptides: A Review of the Activity and Latest Advances

“…In recent years, our group has performed research on the structural modification and antimicrobial activity of PMAPs. According to the structure and mechanism of PMAPs, many scholars have designed multiple novel modified peptides with increased stability and antimicrobial activity (43)(44)(45)(46)(47)(48)(49)(50). This review mainly summarizes the research progress on the structural characteristics and biological activities of PMAPs in recent years.…”

“…Although monomers and dimers show rapid and effective bactericidal activity against most microorganisms, dimeric peptides have a more stable conformation, longer bacteriostatic time, and lower medium sensitivity (34,62). PMAP-37 is an amphiphilic antimicrobial peptide that contains 37 amino acid residues with a molecular weight of 4365.02 Da (38,50), and the amino acid sequence of PMAP-37 is GLLSRLRDFLSDRGRRLGEKIERIGQKIKDLSEFFQS (48,49). PMAP-37 has the highest hydrophobicity and the lowest net charge (22).…”