Alginate Affects Bioactivity of Chimeric Collagen-Binding LL37 Antimicrobial Peptides Adsorbed to Collagen-Alginate Wound Dressings.

Chronic infected wounds cause more than 23,000 deaths annually. Antibiotics and antiseptics are conventionally used to treat infected wounds; however, they can be toxic to mammalian cells, and their use can contribute to antimicrobial resistance. Antimicrobial peptides (AMPs) have been utilized to address the limitations of antiseptics and antibiotics.

Role of lipopolysaccharides and lipoteichoic acids on C-Chrysophsin-1 interactions with model Gram-positive and Gram-negative bacterial membranes.

Antimicrobial peptides (AMPs) are attractive as biomaterial coatings because they have broad spectrum activity against different microbes, with a low likelihood of incurring antimicrobial resistance. Direct action against the bacterial membrane is the most common mechanism of action (MOA) of AMPs, with specific MOAs dependent on membrane composition, peptide concentration, and environmental factors that include temperature. Chrysophsin-1 (CHY1) is a broad spectrum salt-tolerant AMP that is derived from a marine fish.

Mechanistic predictions of the influence of collagen-binding domain sequences on human LL37 interactions with model lipids using quartz crystal microbalance with dissipation.

Modifications of human-derived antimicrobial peptide LL37 with collagen binding domains (CBD-LL37) hold promise as alternatives to antibiotics due to their wider therapeutic ratio than unmodified LL37 when interacting with collagen substrates such as commercial wound dressings. However, CBD-LL37 lipid membrane interaction mechanisms (against both mammalian and bacterial lipids) are not well understood. Our goal was to develop a mechanistic explanation of how CBDs modulate peptide-lipid interactions leading to their observed bioactivities, in order to better understand their potential for clinical applications.

QCM-D characterization of time-dependence of bacterial adhesion.

Quartz crystal microbalance with dissipation monitoring (QCM-D) is becoming an increasingly popular technique that can be employed as part of experimental and modeling investigations of bacterial adhesion. The usefulness of QCM-D derives from this technique's ability to probe binding and interactions under dynamic conditions, in real time. Bacterial adhesion is an important first step in the formation of biofilms, the control of which is relevant to industries that include shipping, water purification, packaging, and biomedical devices.

Concentration-Dependent, Membrane-Selective Activity of Human LL37 Peptides Modified with Collagen Binding Domain Sequences.

Antimicrobial peptides (AMPs) such as LL37 are promising alternatives to antibiotics to treat wound infections due to their broad activity, immunomodulatory functions, and low likelihood of antimicrobial resistance. To deliver LL37 to chronic wounds, we developed two chimeric LL37 peptides with C-terminal collagen binding domains (CBD) derived from collagenase ( cCBD-LL37) and fibronectin ( fCBD-LL37) as a strategy for noncovalent tethering of LL37 onto collagen-based, commercially available wound dressings. The addition of CBD sequences to LL37 resulted in differences in cytotoxicity against human fibroblasts and antimicrobial activity against common wound pathogens.

A QCM-D study of the concentration- and time-dependent interactions of human LL37 with model mammalian lipid bilayers.

The human antimicrobial peptide LL37 is promising as an alternative to antibiotics due to its biophysical interactions with charged bacterial lipids. However, its clinical potential is limited due to its interactions with zwitterionic mammalian lipids leading to cytotoxicity. Mechanistic insight into the LL37 interactions with mammalian lipids may enable rational design of less toxic LL37-based therapeutics.

Collagen tethering of synthetic human antimicrobial peptides cathelicidin LL37 and its effects on antimicrobial activity and cytotoxicity.

Unlabelled: Wound infections, particularly of chronic wounds, pose a substantial challenge for designing antimicrobial dressings that are both effective against pathogens, and do not interfere with wound healing. Due to their broad-spectrum antimicrobial and immunomodulatory activities, naturally-occurring antimicrobial peptides (AMPs) are promising alternative treatments. However, their cytotoxicity at high concentrations and poor stability hinders their clinical use.

Proposed Mechanisms of Tethered Antimicrobial Peptide Chrysophsin-1 as a Function of Tether Length Using QCM-D.

Rising antibiotic resistance has led to a call for the development of alternative antibiotics. Antimicrobial peptides (AMPs) are promising, but their potential has not been fully explored because of toxicity and lack of stability in vivo. Multiple recent studies have focused on surface immobilization of AMPs to maximize antimicrobial activity and stability while mitigating toxicity.