Disclaimer: This dissertation has been written by a student and is not an example of our professional work, which you can see examples of here.

Any opinions, findings, conclusions, or recommendations expressed in this dissertation are those of the authors and do not necessarily reflect the views of UKDiss.com.

Dermcidin’s Mechanism of Action to Destroy and Kill Bacterial Species

1446 words (6 pages) Dissertation

10th Dec 2019 Dissertation Reference this

Tags: Microbiology

Dermcidin: Epidermal Defense

Introduction:

Dermcidin is one of the first responder peptides for defence against bacteria. Dermcidin is a small, 46 armino acid, peptide that folds into an α-helix(1). The α-helix makes 6 copies of itself creating a hexameric helical pore(1). Dermcidin is classified as an antimicrobial peptide that is produced in the sweat glands and secreted through sweat to cover the whole surface of the skin(1). Studies have shown that the dermcidin peptide is able to function optimally in a broad range of pH and salt concentrations that would be found in sweat(2). This shows that sweat plays a significant role in the function and distribution of the peptide. There are two classifications of antimicrobial peptides: cathelicidins and defensins, each of which have similarities in the activity of their antimicrobial properties(3). Cathelicidins are cationic antimicrobial peptides, containing a protected cathelin domain and is a human immune response(4).  Defensins are also cationic antimicrobial peptides but contain 6-8 cysteine residues which make disulfide bridges(5). Defensives can be further categorized into β-defensins, α-defensins, and θ-defensins, β & α-defensins are found in humans. It is the arrangement of the disulfide bridges which determines the categorization of the antimicrobial peptides. Dermcidin does not fit into any of these categories due to its anionic nature, thus it is a unique antimicrobial peptide found on our bodies. This paper will go into details of dermcidin’s mechanism of action to destroy and kill bacterial species. It will also touch upon the current and future research of dermcidin and its properties to create bigger and better antibiotics.

Role in Health & Disease

Antimicrobial peptides not only defend against harmful bacteria, but they also keep the peace between bacteria that coexist with humans. Due to the ability of antimicrobial peptides to attack the unique but vital structural components of bacterial membranes, bacteria are unable to produce an antibiotic resistance to antimicrobial peptides(6). Dermcidin’s sole purpose is to destroy the cellular membranes of microbial species and stopping the development of antibiotic resistance in the bacterial species(6). Dermcidin is found to affect a broad-spectrum of bacterial species, all the way from gram-negative to gram-positive(6). More specifically dermcidin plays a huge role in protecting us from the harmful effects of Staphylococcus epidermidis (S. epidermidis) which is a bacterium that is found in the human flora. S. epidermidis is commonly found in infections caused by lacerations of the skin.  Studies have also shown that dermcidin is expressed continuously through the sweat glands, independent from any sort of skin inflammation, or lacerations(7). It is also known that dermcidin can act upon fungal species, parasites and even enveloped viruses(8). There is global increase of infections caused by multi-resistant bacteria, and even an increase in death caused by these infections(9). Dermcidin’s structure and function is under a large investigation to determine its role in creating new antibiotics for multi-resistant bacteria. Studies have also shown through molecular dynamic simulations how dermcidin forcibly stops the growth of Staphylococcus aureus found on the surface of human skin(6). Dermcidin’s role in health and disease and its unique properties are the driving force for this paper.

History

Levels of Structure

  • Open state transmembrane channels, composed of zinc-connected trimers; antiparallel helix pair

Image of Structure

Mechanism of Function

Antimicrobial peptides are able to target the unique structural features found in microbial membranes, such as the abundant, negatively charge phospholipids.

Interactions with other molecules

Most antimicrobial peptides that are found on our bodies have an overall positive charge. This positive charge assists them in their ability to bind to the abundant phospholipids found in bacterial cells(1). As for Dermcidin the overall charge of the antimicrobial peptide is negative. For dermcidin to be able to interact with the highly negative cell wall of bacteria it interacts with the zinc ions found in sweat(1). Since the zinc ions are positively charge they are able to assist in the attraction of the negative Dermcidin peptide with the negative cell wall of the bacteria. As seen in figure  the zinc ions also assist in stabilizing the repulsion of the negatively charged amino acids. This stabilization created from the interactions of the zinc ions and the negatively charged amino acids allow for complex to form.

Figure  : Structure of dermcidin (PDB:2ymk) showing the interaction of the zinc ions (blue) with the negatively charged amino acids (red)(1).

Current Research

Future Studies

Method of Research

One method that can be used to determine the structure of dermcidin is x-ray crystallography. The purpose of X-ray crystallography is to determine the 3D structure of a molecule, or in this case a protein, from a crystal(10). For protein crystallography the protein of interest must be in its purest form. One of the biggest problems performing X-ray crystallography is whether or not the protein of interest is able to crystalize or not. If it is unable to crystalize this application is unable to be done. Once crystals are produced, they are blasted with an x-ray beam and it is the diffraction patterns that are detected and determine the structure(10). In particular the study conducted by C. Song, et.al, was able to crystalize the dermcidin peptide sequence and perform crystallography to determine the channel structure of dermcidin(6).

One method that was used to determine function of dermcidin is molecular dynamics simulations. Molecular dynamics simulation is a computational method that calculates the time dependant behaviour of a molecular system(11). Through molecular dynamics simulations scientists are able to obtain information about the fluctuations and conformational changes found in proteins(11). Often molecular dynamics simulations are paired with x-ray crystallography and NMR experiments(11). The study conducted by C. Song at.al, was able to use molecular dynamics simulation to determine the function of the ion-transfer channel and dermcidin’s interactions with the negatively charged bacterial-like bilayers(6).

Figure   : Figure  shows the information given by computational electrophysiology and molecular dynamics simulations. A) Shows dermcidin’s tilt in three 250-ns single bilayer molecular dynamics simulations. B) Shows that water distributions (red/white) in and around dermcidin, view shown along the channel axis. C) Shows that path in which a Cl ion (red) passes through the channel, arrows showing the direction of passage. D) Shows that data obtained from computational electrophysiology simulations (6).

One method that can be used to determine the conditions under which the protein of interest is expressed is through immunohistochemistry. Immunohistochemistry is a technique that uses specific antibodies that will specifically bind to a target antigen, this allows for the detection of specific proteins in tissues(12). A study was performed using immunohistochemistry on healthy human skin, along with tissues affected by inflammatory skin diseases, such as psoriasis and lichen planus to determine if dermcidin is an inducible protein(7). The results from this study showed that dermcidin was constantly produced in the sweat glands, and was not induced by inflammatory skin diseases(7).

Figure   : Figure   shows the immunohistochemistry of dermcidin (a-d) and β-defensin (e-h) protein expression. Pictures a and e show health human skin, pictures b and f show a skin biopsy with palmar, c and g show a skin biopsy with psoriasis, and picture d and h show a skin biopsy with lichen planus(7).

Bibliography

 

 

 

Cite This Work

To export a reference to this article please select a referencing stye below:

Reference Copied to Clipboard.
Reference Copied to Clipboard.
Reference Copied to Clipboard.
Reference Copied to Clipboard.
Reference Copied to Clipboard.
Reference Copied to Clipboard.
Reference Copied to Clipboard.

Related Services

View all

DMCA / Removal Request

If you are the original writer of this dissertation and no longer wish to have your work published on the UKDiss.com website then please: