Description

LL-37 is a 37-residue, amphipathic, helical peptide found throughout the body and has been shown to exhibit a broad spectrum of antimicrobial activity.

The figure show an electrostatic surface plot and a cartoon representation of LL-37, stressing the amphipathic nature of the peptide.

The antimicrobial peptides (AMPs) are present in all species investigated. They form an important part of innate immunity, protecting the organism from infection by directly killing invading bacteria. Since pathogenic microorganism show an increasing tendency to be immune against common antibiotics, AMPs carry remarkable pharmaceutical promise as next-generation antibiotics.



The electron micrographs below show how a bacterium is affected by LL-37, a human antimicrobial peptide. The bacterium dies if a threshold called 'minimum inhibitory concentration' (MIC) is reached. Even at concentrations below the MIC, the bacterium shows visible damage.

The exact mechanism by which AMPs kill microorganisms is still under debate. The cartoon below summarizes aspects known for the action of AMPs.

It has been found to have additional defensive roles such as regulating the inflammatory response and chemo-attracting cells of the adaptive immune system to wound or infection sites, binding and neutralizing LPS, and promoting re-epthelialization and wound closure.
Ref and figures: Ulrich et al., 2006; Ramanculov et al., 2001

Assembly

Results

Modelling

Looking forward

At the beginning, our idea was to use the LL 37 cathelicidin as a toxin, to kill the bacteria from inside. Unfortunately this approach was unsuccessfully as the LL 37 does not kill the bacteria.

We thought to use the LL 37 in another way, combined with the T4 holin, (BBa_K112000) a small bacteriophage-encoded proteins that accumulate during the period of late-protein synthesis after infection and cause lysis of the host cell at a precise genetically programmed time.

The rational of this construct is to create a synergic action were the holin creates the pores through which the LL 37 can reach his target.

Link to the Registry