AUTHOR=Nepal Anala , Ræder Synnøve Brandt , Søgaard Caroline Krogh , Haugan Maria Schei , Otterlei Marit 

TITLE=Broad-Spectrum Antibacterial Peptide Kills Extracellular and Intracellular Bacteria Without Affecting Epithelialization

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.764451

DOI=10.3389/fmicb.2021.764451

ISSN=1664-302X

ABSTRACT=<p>New antibacterial drugs with novel modes of action are urgently needed as antibiotic resistance in bacteria is increasing and spreading throughout the world. In this study, we aimed to explore the possibility of using APIM-peptides targeting the bacterial β-clamp for treatment of skin infections. We selected a lead peptide, named betatide, from five APIM-peptide candidates based on their antibacterial and antimutagenic activities in both G<sup>+</sup> and G<sup>–</sup> bacteria. Betatide was further tested in minimal inhibitory concentration (MIC) assays in ESKAPE pathogens, in <italic>in vitro</italic> infection models, and in a resistance development assay. We found that betatide is a broad-range antibacterial which obliterated extracellular bacterial growth of methicillin-resistant <italic>Staphylococcus epidermidis</italic> (MRSE) in cell co-cultures without affecting the epithelialization of HaCaT keratinocytes. Betatide also reduced the number of intracellular <italic>Staphylococcus aureus</italic> in infected HaCaT cells. Furthermore, long-time exposure to betatide at sub-MICs induced minimal or no increase in resistance development compared to ciprofloxacin and gentamicin or ampicillin in <italic>S. aureus</italic> and <italic>Escherichia coli</italic>. These properties support the potential of betatide for the treatment of topical skin infections.</p>