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Tribolium castaneum defensin 1 kills Moraxella catarrhalis in an in vitro infection model but does not harm commensal bacteria

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posted on 22.06.2021, 14:40 by Wilhelm Bertrams, Nora S. Lindhauer, Marie Christin Rieke, Anne Paas, Kerstin Hoffmann, Brandon Greene, Alexander Visekruna, Andreas Vilcinskas, Kerstin Seidel, Bernd Schmeck

Moraxella catarrhalis is a bacterial pathogen that causes respiratory tract infections in humans. The increasing prevalence of antibiotic-resistant M. catarrhalis strains has created a demand for alternative treatment options. We therefore tested 23 insect antimicrobial peptides (AMPs) for their activity against M. catarrhalis in a human in vitro infection model with primary macrophages, and against commensal bacteria. Effects on bacterial growth were determined by colony counting and growth curve analysis. The inflammatory macrophage response was characterized by qPCR and multiplex ELISA. Eleven of the AMPs were active against M. catarrhalis. Defensin 1 from the red flour beetle Tribolium castaneum significantly inhibited bacterial growth and reduced the number of colony forming units. This AMP also showed antibacterial activity in the in vitro infection model, reducing cytokine expression and release by macrophages. Defensin 1 had no effect on the commensal bacteria Escherichia coli and Enterococcus faecalis. However, sarcotoxin 1 C from the green bottle fly Lucilia sericata was active against M. catarrhalis and E. coli, but not against E. faecalis. The ability of T. castaneum defensin 1 to inhibit M. catarrhalis but not selected commensal bacteria, and the absence of cytotoxic or inflammatory effects against human blood-derived macrophages, suggests this AMP may be suitable for development as a new therapeutic lead against antibiotic-resistant M. catarrhalis.

Funding

Parts of this work were 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, German Center for Infectious Disease Research (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.

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