Novel Arginine End-Tagging Antimicrobial Peptides to Combat Multidrug-Resistant Bacteria

Abstract

The emergence of multidrug-resistant microorganisms has been termed one of the most common global health threats, emphasizing the discovery of new antibacterial agents. To address this issue, we engineered peptides harboring "RWWWR" as a central motif plus arginine (R) end-tagging and then tested them <i>in vitro</i> and <i>in vivo</i>. Our results demonstrate that Pep 6, one of the engineered peptides, shows great potential in combating <i>Escherichia coli</i> bacteremia and the <i>Staphylococcus aureus</i> skin burn infection model, which induces a 62-90% reduction in bacterial burden. Remarkably, after long serial passages of <i>S. aureus</i> and <i>E. coli</i> for 30 days, Pep 6 is still highly efficient in killing pathogens, compared with 64- and 128-fold increase in minimal inhibitory concentrations (MICs) for vancomycin and polymyxin B, respectively. We also found that Pep 6 exhibited robust biofilm-inhibiting activity and eliminated 61.33% of the mature methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) biofilm with concentration in the MIC level. These results suggest that the RWWWR motif and binding of arginine end-tagging could be harnessed as a new agent for combating multidrug-resistant bacteria.