Best-In-Class novel Antimicrobial and Antiseptic peptide

The risk of infections caused by drug-resistant bacterial pathogens is increasing worldwide. Current analyses paint a grim picture: In 2019, about 1.3 million deaths were attributed to antimicrobial resistance (AMR), with another 5.0 million deaths linked to AMR. These figures highlight the need to discover new antibiotics and antiseptic solutions. As an alternative therapeutic approach, researchers are actively exploring the potential of antimicrobial peptides (AMPs). These peptides fight pathogens as integral components of the innate immune system of various organisms. It is believed that their unique mode of action is promising, in which microbial membranes are destroyed. This destruction leads to the rapid elimination of bacteria in a shorter period of time than their growth rate, reducing the likelihood of resistance development. In the past, we have studied the mode of action of different peptides to understand how their structure relates to their function. It became apparent that the challenges lie in the complex interplay between peptides and cell membranes. Building on this knowledge, we are strategically modifying the sequence of OP-145, a derivative of the well-studied human cathelicidin LL-37, to optimise its membrane- disrupting capabilities. Our preliminary results are encouraging and suggest that one of our newly developed peptides has remarkable properties. It exhibits increased selectivity towards bacteria and is non-toxic to human cells. Another advantage of this new peptide is its ability to prevent inflammation. This property is attributed to the interaction with two important components found on the surface of bacteria: lipopolysaccharides (LPS) and lipoteichoic acids (LTA). These tend to trigger inflammatory reactions in bacterial infections. The anti-inflammatory function distinguishes our peptide from conventional antibiotics and makes it suitable for treating rapidly spreading infections that lead to sepsis, a life-threatening condition due to inflammation. Furthermore, our research postulates distinct functional regions within the peptide sequence - one for membrane interaction and another for binding to LTA/LPS. We will characterise these regions and make modifications to strengthen their efficacy in microbe elimination as well as anti-inflammatory function. Ultimately, our goal is to integrate or isolate these dual functions into single peptides with enhanced activity. The goal is to further develop these peptides into effective therapeutic interventions to help fight infections and promote better health outcomes.