Sandbox Reserved 1099: Difference between revisions

Dermcidin is present in the sweat around 1-10 µg/ml and acts like a regulator of the skin flora in the [https://en.wikipedia.org/wiki/Innate_immune_system_ innate immune response] by inhibiting a large range of bacteria (comprising Gram positive and Gram negative) and even fungus. Indeed, microbiology tests showed antimicrobial activity against [https://en.wikipedia.org/wiki/Escherichia_coli_ ''Escherichia coli''], [https://en.wikipedia.org/wiki/Staphylococcus_aureus_ ''Staphylococcus aureus''] and [https://en.wikipedia.org/wiki/Enterococcus_faecalis_ ''Enterococcus faecalis''] additional high fungicidal activity on [https://en.wikipedia.org/wiki/Candida_albicans_ ''Candida albicans''].<ref name="de"> Its antimicrobial activity is effective under broad range of pH and high salt concentrations as the human sweat. The sweat is composed in fact of a big percentage of water and electrolytes such as potassium, calcium, magnesium and zinc ions. This is again a key point different from the others AMPs.<ref name="novel"/>  

The overall negatively charged DCD-1L is a one amino acid longer DCD-1 and shows beside the antimicrobial activity against [https://en.wikipedia.org/wiki/Escherichia_coli_ ''Escherichia coli''], [https://en.wikipedia.org/wiki/Staphylococcus_aureus_ ''Staphylococcus aureus''] and [https://en.wikipedia.org/wiki/Enterococcus_faecalis_ ''Enterococcus faecalis''] additional high fungicidal activity on [https://en.wikipedia.org/wiki/Candida_albicans_ ''Candida albicans''].<ref name="novel"/> The first three amino acids (SSL) up to the 23th amino acids of DCD-1L is a region which appears to be responsible for the antibacterial activity. The killing of bacteria rises significantly after 2 – 3 hours of incubation which is not driven by a permeabilization of the outer nor inner bacterial membrane.<ref> Steffen, H., Rieg, S., Wiedemann, I., Kalbacher, H., Deeg, M., Sahl, H.-G., Peschel, A., Gotz, F., Garbe, C., Schittek, B., 2006. Naturally Processed Dermcidin-Derived Peptides Do Not Permeabilize Bacterial Membranes and Kill Microorganisms Irrespective of Their Charge. Antimicrobial Agents and Chemotherapy 50, 2608–2620. https://doi.org/10.1128/AAC.00181-06 </ref> However, more recently studies revealed new information<ref name="girdles"/>, namely, it was also detected that DCD-1L creates ion channels into the bacterial membranes promoted by Zn²⁺.<ref name="de"> Paulmann, M., Arnold, T., Linke, D., Özdirekcan, S., Kopp, A., Gutsmann, T., Kalbacher, H., Wanke, I., Schuenemann, V.J., Habeck, M., Bürck, J., Ulrich, A.S., Schittek, B., 2012. Structure-Activity Analysis of the Dermcidin-derived Peptide DCD-1L, an Anionic Antimicrobial Peptide Present in Human Sweat. J. Biol. Chem. 287, 8434–8443. https://doi.org/10.1074/jbc.M111.332270 </ref> That is the currently accepted opinion. The complex process of forming such a channel starts with a flat approach to the bacterial membrane. Zn²⁺ stabilizes the slow formation of oligomeric complexes and coordinates the His38 residue. A break up of the oligomeric complex follows, leading to a membrane insertion and ending with a re-oligomerization so that the channel is formed.<ref> Burian, M., Schittek, B., 2015. The secrets of dermcidin action. International Journal of Medical Microbiology 305, 283–286. https://doi.org/10.1016/j.ijmm.2014.12.012 </ref> Another study found further evidence for the membrane insertion but only of the cationic N-terminus of DCD-1L with K6 and K13 could being involved in the channel formation.<ref name="nguyen"/> Finally, computer simulations were able to show that the channel allows [https://en.wikipedia.org/wiki/Aquaporin_ aquaporine]-like characterstics but with 50-fold higher osmotic water permeability coefficients. This leads to a high-conductive channel which creates a flux of mainly anions across the bacterial membrane. In a time scale of less than one second the pivotal transmembrane potential of bacteria will abrogate caused by only a few channels.<ref name="girdles"/>

The first three amino acids (SSL) up to the 23th amino acids of DCD-1L is a region which appears to be responsible for the antibacterial activity. The killing of bacteria rises significantly after 2 – 3 hours of incubation which is not driven by a permeabilization of the outer nor inner bacterial membrane.<ref> Steffen, H., Rieg, S., Wiedemann, I., Kalbacher, H., Deeg, M., Sahl, H.-G., Peschel, A., Gotz, F., Garbe, C., Schittek, B., 2006. Naturally Processed Dermcidin-Derived Peptides Do Not Permeabilize Bacterial Membranes and Kill Microorganisms Irrespective of Their Charge. Antimicrobial Agents and Chemotherapy 50, 2608–2620. https://doi.org/10.1128/AAC.00181-06 </ref> However, more recently studies revealed new information<ref name="girdles"/>, namely, it was also detected that DCD-1L creates ion channels into the bacterial membranes promoted by Zn²⁺.<ref name="de"> Paulmann, M., Arnold, T., Linke, D., Özdirekcan, S., Kopp, A., Gutsmann, T., Kalbacher, H., Wanke, I., Schuenemann, V.J., Habeck, M., Bürck, J., Ulrich, A.S., Schittek, B., 2012. Structure-Activity Analysis of the Dermcidin-derived Peptide DCD-1L, an Anionic Antimicrobial Peptide Present in Human Sweat. J. Biol. Chem. 287, 8434–8443. https://doi.org/10.1074/jbc.M111.332270 </ref> The complex process of forming such a channel starts with a flat approach to the bacterial membrane. Zn²⁺ stabilizes the slow formation of oligomeric complexes and coordinates the His38 residue. A break up of the oligomeric complex follows, leading to a membrane insertion and ending with a re-oligomerization so that the channel is formed.<ref> Burian, M., Schittek, B., 2015. The secrets of dermcidin action. International Journal of Medical Microbiology 305, 283–286. https://doi.org/10.1016/j.ijmm.2014.12.012 </ref> Another study found further evidence for the membrane insertion but only of the cationic N-terminus of DCD-1L with K6 and K13 could being involved in the channel formation.<ref name="nguyen"/> Finally, computer simulations were able to show that the channel allows aquaporine-like characterstics but with 50-fold higher osmotic water permeability coefficients. This leads to a high-conductive channel which creates a flux of mainly anions across the bacterial membrane. In a time scale of less than one second the pivotal transmembrane potential of bacteria will abrogate caused by only a few channels.<ref name="girdles"/>