Comparative efficacy analysis of anti-microbial peptides, LL-37 and indolicidin upon conjugation with CNT, in human monocytes

Abstract

BackgroundAntimicrobial peptides (AMPs) have the potential to serve as an alternative to antibiotic. AMPs usually exert bactericidal activity via direct killing of microbial pathogens. Reports have proposed that by harnessing innate immune activation, AMPs can regulate pathogen invasion and may control infection. It has been reported that AMPs could be utilized to activate the innate mucosal immune response in order to eliminate pathogenic infections. This way of controlling pathogen infection, by activating host immunity, confers the potential to the select AMPs to alleviate the problem of antibiotic resistance. Among various AMPs tested LL-37 and indolicidin, showed promise to be potential candidates for eliciting enhanced host innate immune responses. LL-37 and indolicidin had exhibited substantial innate immune activation in both human and murine macrophages. Dosage for each of the AMPs, however, was high with adverse side effects.ResultsIn this study, we reported that upon conjugation with carbon nanotubes (CNT), each AMP remained biologically functional at a concentration that was 1000-fold less than the dosage required for free AMP to remain active in the cells.ConclusionsCurrent study also revealed that while indolicidin induced signalling events mediated through the TNFRSF1A pathway in THP1 cells, followed by activation of NFκB and c-JUN pathways, treatment of cells with LL-37 induced signalling events by activating IL1R, with subsequent activation of NFκB and NFAT2. Thp1 cells, primed with CNT conjugated LL-37 or indolicidin, are protected against Salmonella typhimurium infection at 16 h post challenge.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-017-0278-1) contains supplementary material, which is available to authorized users.

Recent advances in the design of antimicrobial peptide conjugates

“…122 Recently, Pradhan and colleagues (2017) conjugated LL-37 and indolicidin to short multi-walled carbon nanotubes (SMCNTs); the in vitro immunoregulatory activity of nano-conjugates was significantly higher than that of the dissociated forms of indolicidin and LL-37, and peptide activity was maintained even at a concentration that is 1000 times lower (0.02 μg mL −1 of nano-conjugates and 20 μg mL −1 of free peptides). 75…”

Detecting the Mechanism of Action of Antimicrobial Peptides by Using Microscopic Detection Techniques

“…Some of these AMPs, such as alamethicin, porcine protegrin-1, indolicidin, temporin-She, and AP-64, are considered cytotoxic for human use, while the rest of the AMPs (magainin 2, HBD2, LL-37, nisin, Pro10-1D, and protein-glutamine gamma-glutamyltransferase 2) are considered less toxic and safe to use. Among all these safe-to-use AMPs, nisin is used extensively in clinical trials [ 25 , 26 ]. More in vitro and in vivo clinical trials are required to further explore its safety.…”

Nanostructured Antimicrobial Peptides: Crucial Steps of Overcoming the Bottleneck for Clinics

“…It has been documented that the surface of CNTs can decorate various functional groups and provides binding sites, thus, improving the dispersibility and biocompatibility of uploaded drugs ( Zhang et al, 2012 ). Pradhan et al (2017) reported that SM-CNTs conjugated to LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) or indolicidin by the use of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and N-hydroxysuccinimide (EDC-NHS) conjugation protocol to impair side effects. The results demonstrated that the two-peptide conjugation with CNT was 1,000-fold lower than the dosage of free AMPs required for intracellular biological functions, suggesting that SM-CNTs improved the immune-modulatory efficacy of LL-37 and indolicidin, while efficiently reducing the dosage of peptide agents.…”