Antibacterial activity of a Tribolium castaneum defensin in an in vitro infection model of Streptococcus pneumoniae

Virulence. 2019 Dec;10(1):902-909. doi: 10.1080/21505594.2019.1685150.

Abstract

Streptococcus pneumoniae (S. pneumoniae) is the most common bacterial cause of community-acquired pneumonia. Increasing rates of antibiotic-resistant S. pneumoniae strains impair therapy and necessitate alternative treatment options. In this study, we analysed insect-derived antimicrobial peptides (AMPs) for antibacterial effects on S. pneumoniae in a human in vitro infection model.AMP effects on bacterial growth were examined by colony forming unit (CFU)-assays, and growth curve measurements. Furthermore, cytotoxicity to primary human macrophages was detected by measuring lactate-dehydrogenase release to the supernatant. One AMP (Defensin 1) was tested in a model of primary human monocyte-derived macrophages infected with S. pneumoniae strain D39 and a multi-resistant clinical isolate. Inflammatory reactions were characterised by qPCR and multiplex-ELISA.In total, the antibacterial effects of 23 AMPs were characterized. Only Tribolium castaneum Defensin 1 showed significant antibacterial effects against S. pneumoniae strain D39 and a multi-resistant clinical isolate. During in vitro infection of primary human macrophages with S. pneumoniae D39, Defensin 1 displayed strong antibacterial effects, and consequently reduced bacteria-induced cytokine expression and release.In summary, Tribolium castaneum Defensin 1 showed profound antibacterial effectivity against Streptococcus pneumoniae D39 and a multi-resistant clinical isolate without unwanted cytotoxic or inflammatory side effects on human blood-derived macrophages.

Keywords: Antimicrobial peptides; Streptococcus pneumoniae; antibiotic resistance; defensin; inflammation; insect; macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Cells, Cultured
  • Defensins / pharmacology*
  • Drug Resistance, Multiple, Bacterial
  • Humans
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / microbiology*
  • Microbial Sensitivity Tests
  • Pneumococcal Infections / microbiology
  • Streptococcus pneumoniae / drug effects*
  • Tribolium / chemistry*

Substances

  • Anti-Bacterial Agents
  • Defensins

Grant support

Parts of this work have been funded by the Kempkes Foundation (04/2016) to WB, the Bundesministerium für Bildung und Forschung (e:Med CAPSYS - FKZ 01ZX1604E; JPI-AMR – FKZ 01Kl1702; ERACoSysMed2 – SysMed-COPD – FKZ 031L0140, http://www.bmbf.de/) to BS, Deutsches Zentrum für Infektionsforschung (DZIF) to NSL, Deutsche Forschungsgemeinschaft (SFB/TR-84 TP C01; http://www.sfb-tr84.de/) to BS, Hessisches Ministerium für Wissenschaft und Kunst (LOEWE Medical RNomics - FKZ 519/03/00.001-(0003); http://www.proloewe.de/medicalrnomics) to BS.