Sandbox Reserved 1099: Difference between revisions
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== Antimicrobial activity == | == Antimicrobial activity == | ||
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. 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"/>. | 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''] . 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 12 DCD-1L-derived peptides described in the expression and maturation part play a role in the modulation of the immune response. For exemple, some of them seems to be more active against ''E. coli'' or ''S.aureus'' than DCD-1L. This is the case of SSL-29, SSL-25 and LEK-24 peptides. Therefor the antimicrobial defense of humans does not stop at the point of DCD-1L but is more likely modulated by further proteolytic processes (e.g. by CatD) to maintain a healthy innate immune defense on the human skin <ref name="baechle"/>. | The 12 DCD-1L-derived peptides described in the expression and maturation part play a role in the modulation of the immune response. For exemple, some of them seems to be more active against ''E. coli'' or ''S.aureus'' than DCD-1L. This is the case of SSL-29, SSL-25 and LEK-24 peptides. Therefor the antimicrobial defense of humans does not stop at the point of DCD-1L but is more likely modulated by further proteolytic processes (e.g. by CatD) to maintain a healthy innate immune defense on the human skin <ref name="baechle"/>. | ||
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 Zn<sup>2+</sup>.<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. Zn<sup>2+</sup> 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"/> | |||
12 DCD-1L-derived peptides by CatD, a carboxypeptidase and an endoprotease are present in human sweat. Some of them have no antimicrobial effect, however, one appears to be more active against ''E. coli'' than DCD-1L. Therefor the antimicrobial defense of humans does not stop at the point of DCD-1L but is more likely modulated by further proteolytic processes (e.g. by CatD) to maintain a healthy innate immune defense on the human skin.<ref name="baechle"/> | 12 DCD-1L-derived peptides by CatD, a carboxypeptidase and an endoprotease are present in human sweat. Some of them have no antimicrobial effect, however, one appears to be more active against ''E. coli'' than DCD-1L. Therefor the antimicrobial defense of humans does not stop at the point of DCD-1L but is more likely modulated by further proteolytic processes (e.g. by CatD) to maintain a healthy innate immune defense on the human skin.<ref name="baechle"/> | ||
