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

<i>Moraxella catarrhalis</i> is a bacterial pathogen that causes respiratory tract infections in humans. The increasing prevalence of antibiotic-resistant <i>M. catarrhalis</i> strains has created a demand for alternative treatment options. We therefore tested 23 insect antimicrobial peptides (AMPs) for their activity against <i>M. catarrhalis</i> in a human <i>in vitro</i> 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 <i>M. catarrhalis</i>. Defensin 1 from the red flour beetle <i>Tribolium castaneum</i> significantly inhibited bacterial growth and reduced the number of colony forming units. This AMP also showed antibacterial activity in the <i>in vitro</i> infection model, reducing cytokine expression and release by macrophages. Defensin 1 had no effect on the commensal bacteria <i>Escherichia coli</i> and <i>Enterococcus faecalis</i>. However, sarcotoxin 1 C from the green bottle fly <i>Lucilia sericata</i> was active against <i>M. catarrhalis</i> and <i>E. coli</i>, but not against <i>E. faecalis</i>. The ability of <i>T. castaneum</i> defensin 1 to inhibit <i>M. catarrhalis</i> 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 <i>M. catarrhalis</i>.