The Potential of Human Peptide LL-37 as an Antimicrobial and Anti-Biofilm Agent

Abstract

The rise in antimicrobial resistant bacteria threatens the current methods utilized to treat bacterial infections. The development of novel therapeutic agents is crucial in avoiding a post-antibiotic era and the associated deaths from antibiotic resistant pathogens. The human antimicrobial peptide LL-37 has been considered as a potential alternative to conventional antibiotics as it displays broad spectrum antibacterial and anti-biofilm activities as well as immunomodulatory functions. While LL-37 has shown promising results, it has yet to receive regulatory approval as a peptide antibiotic. Despite the strong antimicrobial properties, LL-37 has several limitations including high cost, lower activity in physiological environments, susceptibility to proteolytic degradation, and high toxicity to human cells. This review will discuss the challenges associated with making LL-37 into a viable antibiotic treatment option, with a focus on antimicrobial resistance and cross-resistance as well as adaptive responses to sub-inhibitory concentrations of the peptide. The possible methods to overcome these challenges, including immobilization techniques, LL-37 delivery systems, the development of LL-37 derivatives, and synergistic combinations will also be considered. Herein, we describe how combination therapy and structural modifications to the sequence, helicity, hydrophobicity, charge, and configuration of LL-37 could optimize the antimicrobial and anti-biofilm activities of LL-37 for future clinical use.

Efficacy of Cathelicidin LL-37 in an MRSA Wound Infection Mouse Model

“…Bacterial lysis occurs due to altered permeability of the bacterial membrane with transmembrane pores [22]. In fact, LL-37 showed a broad-spectrum against several different pathogens, such as Gram-positive and Gram-negative bacteria [23], fungi [24][25][26] and viruses [27]. Moreover, LL-37 revealed other biological activities, such as regulation of responses to inflammation, showing both pro-inflammatory and anti-inflammatory effects [28].…”

Candida albicans Sfp1 Is Involved in the Cell Wall and Endoplasmic Reticulum Stress Responses Induced by Human Antimicrobial Peptide LL-37

“…Mutants lacking HacA in Aspergillus fumigatus and Hxl1 in Cryptococcus neoformans , the homologs of Hac1, attenuate virulence in mouse models of infection [ 71 , 72 ]. LL-37 is a multifunctional AMP commonly found at mucosal surfaces of humans and plays an important role in the first line of defense against microbial infection [ 17 , 73 ]. Our previous studies showed that LL-37 targets the cell wall and affects C. albicans adhesion to abiotic and biotic surfaces, including oral epidermal cells and mouse bladder mucosa [ 19 , 22 ].…”

The Antibiofilm Nanosystems for Improved Infection Inhibition of Microbes in Skin

“…Mannosides target the bacterial adhesin of FimH to prevent infection by reducing bacterial colonization via adhesion suppression [75]. LL-37 is a cathelicidin-derived broad spectrum antimicrobial peptide that has been investigated to restrain biofilms by preventing bacterial attachment to the surface [76]. LL-37 also displays broad spectrum antibacterial activities and immunomodulatory functions.…”