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.

Bacterial resistance induced by the use of antibiotics has provided a chance for the development of antimicrobial peptides (AMPs), and modification of AMPs to enhance the antibacterial activity or stability has become a research focus. PMAP‐37 is an AMP isolated from porcine myeloid marrow, and studies on its modification have not yet been reported. In this study, three PMAP‐37 analogs named PMAP‐37(F9‐R), PMAP‐37(F34‐R), and PMAP‐37(F9/34‐R) were designed by residue substitution to enhance the positive charge. The antimicrobial activity of PMAP‐37 and its analogs in vitro and in vivo were detected. The results showed that compared with PMAP‐37, PMAP‐37(F9‐R) and PMAP‐37(F9/34‐R) exhibited antibacterial activity against S. flexneri CICC21534. Although PMAP‐37(F34‐R) had no antibacterial activity against S. flexneri CICC21534, its minimal inhibitory concentrations (MICs) were significantly lower than those of PMAP‐37 against most bacterial strains. Besides, all PMAP‐37 analogs were pH stable, retaining stable antibacterial activity after treatment with solution from pH 2 to pH 8/9. In addition, the PMAP‐37 analogs displayed increased thermal stability, and PMAP‐37(F34‐R) retained >60% antibacterial activity after boiling for 2 hours. Furthermore, the PMAP‐37 analogs exhibited impressive therapeutic efficacy in bacterial infections by reducing bacterial burden and inflammatory damage in the lung and liver, resulting in a reduction in mortality. Notably, the therapeutic effect of PMAP‐37(F34‐R) was comparable to that of ceftiofur sodium, and even superior to antibiotics in L. monocytogenes CICC21533 infection model. In conclusion, the PMAP‐37(F34‐R) may be a candidate for the treatment of bacterial infections in the clinic.

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In summary, BPP-IV did not have an effect on specific immune responses, therefore it could not reduce pathological damage in mice lungs; BPP-III provided resistance to the antigen through the cell-mediated immune response; BPP-V enhanced both humoral and cellular immune responses, therefore provided protections against the H9N2 Avian Influenza Virus (AIV). Altogether, BPP-III and BPP-V could be adjuvant candidates for the H9N2 avian influenza vaccine.

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.

Drug-resistant bacteria infections and drug residues have been increasing and causing antibiotic resistance and public health threats worldwide. Antimicrobial peptides (AMPs) are novel antimicrobial drugs with the potential to solve these problems. Here, a peptide based on our previously studied peptide PMAP-36PW was designed via N-terminal myristoylation and referred to as Myr-36PW. The fatty acid modification provided the as-prepared peptide with good stability and higher antimicrobial activity compared with PMAP-36PW in vitro. Moreover, Myr-36PW exhibited effective anti-biofilm activity against Gram-negative bacteria and may kill bacteria by improving the permeability of their membranes. In addition, the designed peptide Myr-36PW could inhibit the bacterial growth of Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa GIM 1.551 to target organs, decrease the inflammatory damage, show an impressive therapeutic effect on mouse pneumonia and peritonitis experiments, and promote abscess reduction and wound healing in infected mice. These results reveal that Myr-36PW is a promising antimicrobial agent against bacterial infections.

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Traditional antibiotics have made great contributions to human health and animal husbandry since the discovery of penicillin in 1928, but bacterial resistance and drug residues are growing threats to global public health due to the long-term uncontrolled application of antibiotics. There is a critical need to develop new antimicrobial drugs to replace antibiotics. Antimicrobial peptides (AMPs) are distributed in all kingdoms of life, presenting activity against pathogens as well as anticancer, anti-inflammatory, and immunomodulatory activities; consequently, they have prospects as new potential alternatives to antibiotics. Porcine myeloid antimicrobial peptides (PMAPs), the porcine cathelicidin family of AMPs, have been reported in the literature in recent years. PMAPs have become an important research topic due to their strong antibacterial activity. This review focuses on the universal trends in the biochemical parameters, structural characteristics and biological activities of PMAPs.