Antimicrobial peptide PMAP-37 analogs: Increasing the positive charge to enhance the antibacterial activity of PMAP-37

Jiangfei Zhou, Liangliang Chen, Yongqing Liu, Tengfei Shen, Cong Zhang, Zhixin Liu, Xiuli Feng, Chen Wang

Research output: Contribution to journalArticle

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 languageEnglish (US)
Article numbere3220
JournalJournal of Peptide Science
Volume25
Issue number12
DOIs
StatePublished - Dec 1 2019
Externally publishedYes

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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

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