Testing Ab Initio Designed Antimicrobial Peptides Against Multi-Drug Resistant Acinetobacter baumannii

Abstract

With the development of drug-resistant bacteria in the past century in response to the overuse of antibiotics, there is a pressing need to develop novel ways to counteract bacteria with the ability to acquire resistance to certain treatments when exposed. Antimicrobial peptides (AMPs) are present in every living organism and remain evolutionarily ancient, meaning that they have been able to prevent bacteria from acquiring resistance to their mechanisms for millennia, whereas antibiotics developed in the 20th century caused widespread antibiotic resistance within decades. AMPs have been shown to have therapeutic potential for their ability to kill pathogens while preventing them from developing resistance. In this study, we tested six ab initio-designed peptides for their effectiveness against the multidrug-resistant, gram-negative Acinetobacter baumannii, an increasingly prominent hospital-derived pathogen that primarily affects patients with compromised immune systems. We tested one peptide (termed HRZN-15) for its ability to prevent this bacterium from acquiring resistance by exposing it to a sub-MIC concentration and testing the peptide’s MIC on the exposed pathogen every five days over a fifteen-day period. We found that the ab initio-designed peptides were able to inhibit Acinetobacter baumannii’s growth and that the bacteria acquired resistance to HRZN-15 much slower and less effectively compared to colistin. Based on our findings, these peptides have the potential for therapeutic use.