Evaluation of antimicrobial peptide LL-37 for treatment of Staphylococcus aureus biofilm on titanium plate

Abstract

The antimicrobial peptide LL-37 belongs to the cathelicidin family and is one of the few human bactericidal peptides with potent antistaphylococcal activity. Staphylococcus aureus is one of the main infection bacteria in orthopedic implant therapy. Biofilm formation after bacterial infection brings more and more severe test for clinical antiinfection treatment.However, there are few studies on LL-37 in S. aureus infection of prosthesis. In this work, addition to research the antibacterial activity and the inhibitory effect on bacterial adhesion of LL-37, an in vitro model of S. aureus biofilm formation on titanium alloy surface was established to observe the inhibitory effect of LL-37.The results showed that LL-37 has a strong antibacterial effect on S. aureus in vitro, and the minimum inhibitory concentration (MIC) is about 0.62 μΜ. Moreover, LL-37 has significant impact on the adhesion of S. aureus when the concentration ≥0.16 μM and significant anti-staphylococcal biofilm effects on static biofilm models at the concentration of 0.31 to 10 μM. Additionally, LL-37 at 5 μM had a significant destructive effect on S. aureus biofilm (P < .05) that formed on the titanium alloy surface.This study further confirmed the role of LL-37 in the process of S. aureus infection, including antimicrobial activities, inhibition of bacterial adhesion, and inhibition of mature biofilm. LL-37 can significantly destroy the stable biofilm structure on the titanium alloy surface in vitro, which may provide a new way for refractory infection caused by S. aureus in titanium alloy prosthesis infection.

Rational design of bifunctional chimeric peptides that combine antimicrobial and titanium binding activity

“…Thus, an antimicrobial effect of the herein described peptides would be highly beneficial for a future treatment of these critical pathogens. As controls, we included not only MGD2 but also LL37, which was very recently investigated concerning its potency to prevent S. aureus biofilm formation on titanium alloy surfaces 24 . After incubating the peptides for 2 h with the respective strains, a colony formation assay was performed.…”

“…As controls, we included not only MGD2 but also LL37, which was very recently investigated concerning its potency to prevent S. aureus biofilm formation on titanium alloy surfaces. 24 After incubating the peptides for 2 h with the respective strains, a colony formation assay was performed. For all tested peptides, a steady decrease in bacterial viability of S. aureus was observed (Figure 2).…”

A Comprehensive Review of Recent Research into the Effects of Antimicrobial Peptides on Biofilms—January 2020 to September 2023

“…The human cathelicidin LL-37 was one of the popular AMPs to be studied during the review period, with LL-37 being one of the few human bactericidal peptides with potent anti-staphylococcal activity (one of the main bacteria associated with orthopeadic implant infections). Using in vitro studies and static biofilm models, Wei et al showed that LL-37 had significant anti-staphylococcal effects and a 'destructive effect' on S. aureus biofilm formed on a titanium alloy surface (as a proxy for a prosthesis) [99]. Wuersching et al examined the effects of LL-37 and human lactoferricin AMPs on anaerobic biofilms associated with oral diseases [100].…”

Molecular Aspects of the Functioning of Pathogenic Bacteria Biofilm Based on Quorum Sensing (QS) Signal-Response System and Innovative Non-Antibiotic Strategies for Their Elimination

“…The best-studied NAMP produced in the human body is cathelicidin LL-37, termed host defence enzymes, which possesses antimicrobial and antibiofilm activities against a broad spectrum of MDR strains [ 171 , 217 ]. A large number of studies regarding antimicrobial/antibiofilm properties of the LL-37 are focused on strains in which antibiotic resistance is a serious problem, including P. aeruginosa [ 218 ], S. aureus [ 219 ], S. epidermidis [ 220 ], Streptococcus pneumoniae [ 221 ], Streptococcus pyogenes [ 222 ], Acinetobacter baumannii [ 223 ], E. coli [ 224 ], K. pneumonia [ 225 ], Helicobacter pylori [ 226 ], and Aggregatibacter actinomycetemcomitans [ 227 ]. In P. aeruginosa PAO1 grown under biofilm conditions in a flow cell, global gene expression analysis revealed that 4-day exposure to LL-37 (4 µg/mL) led to the downregulation of 475 genes, including QS-controlled genes such as lasl and rhlR [ 228 ].…”