Sandbox Reserved 1099: Difference between revisions
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==Homology== | ==Homology== | ||
The dermcidin peptide sequence has no homology with other known [https://en.wikipedia.org/wiki/Antimicrobial_peptides_ antimicrobial peptide](shortened to AMP). There are two types of AMP, the anionic antimicrobial peptide (AAMP) and the cationic one (CAMP). These two AMP are completing themselves as they reach there optimum under different conditions. Despite AAMP are rare and infrequent in humans, dermcidin is the one of the most analysed AAMP. | The dermcidin peptide sequence has no homology with other known [https://en.wikipedia.org/wiki/Antimicrobial_peptides_ antimicrobial peptide](shortened to AMP). There are two types of AMP, the anionic antimicrobial peptide (AAMP) and the cationic one (CAMP). These two AMP are completing themselves as they reach ''there optimum'' under different conditions. Despite AAMP are rare and infrequent in humans, dermcidin is the one of the most analysed AAMP. | ||
Two classes of mammalian and cationic antimicrobial peptides exist: | Two classes of mammalian and cationic antimicrobial peptides exist: | ||
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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 (Gram positive: [https://en.wikipedia.org/wiki/Staphylococcus_aureus_ ''Staphylococcus aureus''], [https://en.wikipedia.org/wiki/Enterococcus_faecalis_ ''Enterococcus faecalis'']; Gram negative: [https://en.wikipedia.org/wiki/Escherichia_coli_ ''Escherichia coli'']) and even fungus ([https://en.wikipedia.org/wiki/Candida_albicans_ ''Candida albicans'']).<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> Its antimicrobial activity is effective under a broad range of pH and high salt concentrations as the human sweat possesses. The sweat is composed of a big percentage of water and electrolytes such as potassium, calcium, magnesium and zinc ions. This is again a principle difference to the other 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 (Gram positive: [https://en.wikipedia.org/wiki/Staphylococcus_aureus_ ''Staphylococcus aureus''], [https://en.wikipedia.org/wiki/Enterococcus_faecalis_ ''Enterococcus faecalis'']; Gram negative: [https://en.wikipedia.org/wiki/Escherichia_coli_ ''Escherichia coli'']) and even fungus ([https://en.wikipedia.org/wiki/Candida_albicans_ ''Candida albicans'']).<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> Its antimicrobial activity is effective under a broad range of pH and high salt concentrations as the human sweat possesses. The sweat is composed of a big percentage of water and electrolytes such as potassium, calcium, magnesium and zinc ions. This is again a principle difference to the other 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 example, 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. Indeed, 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.<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> Therefore 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 example, 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. Indeed, 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.<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> Therefore 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"/> | ||
More recently studies revealed 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 [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 predominantly 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"/> | More recently studies revealed 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 [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 predominantly 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"/> | ||
