Abstract
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.
Original language | English (US) |
---|---|
Article number | e3220 |
Journal | Journal of Peptide Science |
Volume | 25 |
Issue number | 12 |
DOIs | |
State | Published - Dec 1 2019 |
Externally published | Yes |
Keywords
- antibacterial activity
- antimicrobial susceptibility testing
- PMAP-37
- positive charges
- stability
ASJC Scopus subject areas
- Structural Biology
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmacology
- Drug Discovery
- Organic Chemistry