A Novel Cryptic Clostridial Peptide That Kills Bacteria by a Cell Membrane Permeabilization Mechanism
Monika Szadkowska, Michał Olewniczak, Anna Kłoska, Elżbieta Jankowska, Małgorzata Kapusta, B Rybak, Dariusz Wyrzykowski, Wioletta Żmudzińska, Artur Giełdoń, Aleksandra M. Kocot, Anna‐Karina Kaczorowska, Łukasz Nierzwicki, Joanna Makowska, Tadeusz Kaczorowski, Magdalena Płotka
Abstract
Antibiotic resistance is rising rapidly among pathogenic bacteria, becoming a global public health problem that threatens the effectiveness of therapies for many infectious diseases. In this respect, antimicrobial peptides appear to be an interesting alternative to combat bacterial pathogens. Here, we report the characteristics of an antimicrobial peptide (of 30 amino acids) derived from the clostridial LysC enzyme. The peptide showed killing activity against clinical strains of Gram-positive and Gram-negative pathogens. Experimental data and computational modeling showed that this peptide forms transmembrane pores, directly engaging the negatively charged phospholipids of the bacterial cell membrane. Consequently, dissipation of the electrochemical gradient across cell membranes affects many vital processes, such as ATP synthesis, motility, and transport of nutrients. This kind of dysfunction leads to the loss of bacterial viability. Our firm conviction is that the presented study will be a helpful resource in searching for novel antimicrobial peptides that could have the potential to replace conventional antibiotics.