Development of Antimicrobial Peptides Based on Limulus Anti-Lipopolysaccharide Factor (LALF)

Since the 1990s, antimicrobial peptides (AMP) are attracting increasing attention from the medical community, due to the worldwide proliferation of antibiotic resistant human pathogens. According to a report of the World Health Organisation (WHO) “The world is running out of antibiotics”, many experts warn about the possibility that mankind may soon return to the pre-antibiotic era (Brandenburg and Schurholz, World J Biol Chem 6:71–7, 2015). Of particular concern are bacterial pathogens that belong to the so-called ESKAPE group, an acronym formed from the initial letter of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii; Pseudomonas aeruginosa, and Enterobacter spp (Tommasi et al., Nat Rev Drug Discov 14:529–42, 2015). A number of AMPs have been and are now being evaluated in clinical trials. Table 19.1 shows selected examples from preclinic to late state clinical development. The number of submitted patent applications, claiming therapeutic applications of AMPs, has increased in recent years (Kang et al., J Microbiol 55:1–12, 2017). However, as already pointed out by Kosikowska and Lesner (Expert Opin Ther Pat 26:689–702, 2016), “the existing discord between the upcoming list of antimicrobial peptides claimed in the patents or related scientific articles as the potent drug candidates and the frequent failures of AMPs in clinical trials emphasize the need of a better understanding of their pleiotropic nature and mechanisms of host defense in general” (Naafs, Biomed J Sci Tech Res, 2018). The successful commercialization of AMPs such as Polymyxin or Fuzeon®, DALVANCE®, however, give some encouragement that the development of AMPs as a novel class of antibiotics is still considered viable. In this chapter, mainly AMP based on Limulus and other anti-lipopolysaccharide (LPS) factors are presented, particularly synthetic anti-LPS peptides (SALP) which exhibit very promising properties with respect to the fight against severe bacterial infections such as sepsis.