Constitutive expression of antimicrobial peptide PR-39 in transgenic mice significantly enhances resistance to bacterial infection and promotes growth

Transgenic Res. 2018 Oct;27(5):409-422. doi: 10.1007/s11248-018-0084-z. Epub 2018 Jul 12.

Abstract

Use of huge amounts of antibiotics in farm animal production has promoted the prevalence of antibiotic-resistant bacteria, which poses a serious threat to public health. Therefore, alternative approaches are needed to reduce or replace antibiotic usage in the food animal industry. PR-39 is a pig-derived proline-rich antimicrobial peptide that has a broad spectrum of antibacterial activity and a low propensity for development of resistance by microorganisms. To test whether ubiquitous expression of PR-39 in transgenic (TG) mice can increase resistance against bacterial infection, we generated TG mice that ubiquitously express a pig-derived antimicrobial peptide PR-39 and analyzed their growth and resistance to infection of the highly pathogenic Actinobacillus pleuropneumoniae (APP) isolated from swine. The growth performance was significantly increased in TG mice compared with their wild-type (WT) littermates. After the APP challenge, TG mice exhibited a significantly higher survival rate and significantly lower tissue bacterial load than WT littermates. Furthermore, the tissue lesion severity that resulted from APP infection was milder in TG mice than that in their WT littermates. This study provides a good foundation for the development of PR-39-expressing TG animals, which could reduce the use of antibiotics in the farm animal industry.

Keywords: Actinobacillus pleuropneumoniae infection; Antimicrobial peptides; Growth; PR-39; Transgenic animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinobacillus Infections / genetics*
  • Actinobacillus Infections / microbiology
  • Actinobacillus Infections / mortality
  • Actinobacillus pleuropneumoniae / pathogenicity
  • Animals
  • Antimicrobial Cationic Peptides / genetics*
  • Antimicrobial Cationic Peptides / metabolism
  • Bacterial Load
  • Disease Resistance / genetics*
  • Female
  • Gene Expression
  • HEK293 Cells
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic* / growth & development
  • Mice, Transgenic* / microbiology
  • Promoter Regions, Genetic
  • Swine

Substances

  • Antimicrobial Cationic Peptides
  • PR 39