| Structural highlights
Function
TPB_RANTE Amphipathic alpha-helical antimicrobial peptide with potent activity against Gram-positive bacteria, weak activity against Gram-negative bacteria, and moderate activity against fungi (PubMed:27351824, PubMed:30718667, PubMed:9022710). Mainly acts by causing membrane permeabilization, but is unable to forme pore-like openings (Probable). Is also able to penetrate eukaryotic cells (keratinocytes), and kill intracellular S.aureus (both wild-type and MRSA) without injuring host cells (PubMed:24514087). Shows inhibitory effect on biofilm formation of Gram-positive bacteria, but not of Gram-negative bacteria (PubMed:27351824, PubMed:28443279). Shows antiviral activity against herpes simplex virus 1 (HSV-1) by disrupting the viral envelope (PubMed:29483113). Also displays anti-leishmania activity by damaging parasite membrane (PubMed:15513914, PubMed:25668079). Does not show hemolytic activity (PubMed:15513914, PubMed:28443279, PubMed:9022710). Acts synergistically with temporin-L that improves temporin-1Tb activity by preventing its self-association in lipopolysaccharides (LPS) (PubMed:16867990, PubMed:21586570). In vitro, promotes cell migration and wound healing (PubMed:24514087).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]
Publication Abstract from PubMed
Antimicrobial peptides (AMPs) are a potential source of new molecules to counter the increase in antimicrobial resistant infections but a better understanding of their properties is required to understand their native function and for effective translation as therapeutics. Details of the mechanism of their interaction with the bacterial plasma membrane are desired since damage or penetration of this structure is considered essential for AMPs activity. Relatively modest modifications to AMPs primary sequence can induce substantial changes in potency and/or spectrum of activity but, hitherto, have not been predicted to substantially alter the mechanism of interaction with the bacterial plasma membrane. Here we use a combination of molecular dynamics simulations, circular dichroism, solid-state NMR and patch clamp to investigate the extent to which temporin B and its analogues can be distinguished both in vitro and in silico on the basis of their interactions with model membranes. Enhancing the hydrophobicity of the N-terminus and cationicity of the C-terminus in temporin B improves its membrane activity and potency against both Gram-negative and Gram-positive bacteria. In contrast, enhancing the cationicity of the N-terminus abrogates its ability to trigger channel conductance and renders it ineffective against Gram-positive bacteria while nevertheless enhancing its potency against Escherichia coli. Our findings suggest even closely related AMPs may target the same bacterium with fundamentally differing mechanisms of action.
Minor sequence modifications in temporin B cause drastic changes in antibacterial potency and selectivity by fundamentally altering membrane activity.,Manzo G, Ferguson PM, Gustilo VB, Hind CK, Clifford M, Bui TT, Drake AF, Atkinson RA, Sutton JM, Batoni G, Lorenz CD, Phoenix DA, Mason AJ Sci Rep. 2019 Feb 4;9(1):1385. doi: 10.1038/s41598-018-37630-3. PMID:30718667[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mangoni ML, Saugar JM, Dellisanti M, Barra D, Simmaco M, Rivas L. Temporins, small antimicrobial peptides with leishmanicidal activity. J Biol Chem. 2005 Jan 14;280(2):984-90. PMID:15513914 doi:10.1074/jbc.M410795200
- ↑ Rosenfeld Y, Barra D, Simmaco M, Shai Y, Mangoni ML. A synergism between temporins toward Gram-negative bacteria overcomes resistance imposed by the lipopolysaccharide protective layer. J Biol Chem. 2006 Sep 29;281(39):28565-74. PMID:16867990 doi:10.1074/jbc.M606031200
- ↑ Bhunia A, Saravanan R, Mohanram H, Mangoni ML, Bhattacharjya S. NMR structures and interactions of temporin-1Tl and temporin-1Tb with lipopolysaccharide micelles: mechanistic insights into outer membrane permeabilization and synergistic activity. J Biol Chem. 2011 Jul 8;286(27):24394-406. PMID:21586570 doi:10.1074/jbc.M110.189662
- ↑ Di Grazia A, Luca V, Segev-Zarko LA, Shai Y, Mangoni ML. Temporins A and B stimulate migration of HaCaT keratinocytes and kill intracellular Staphylococcus aureus. Antimicrob Agents Chemother. 2014 May;58(5):2520-7. PMID:24514087 doi:10.1128/AAC.02801-13
- ↑ Eggimann GA, Sweeney K, Bolt HL, Rozatian N, Cobb SL, Denny PW. The role of phosphoglycans in the susceptibility of Leishmania mexicana to the temporin family of anti-microbial peptides. Molecules. 2015 Feb 6;20(2):2775-85. PMID:25668079 doi:10.3390/molecules20022775
- ↑ Maisetta G, Grassi L, Di Luca M, Bombardelli S, Medici C, Brancatisano FL, Esin S, Batoni G. Anti-biofilm properties of the antimicrobial peptide temporin 1Tb and its ability, in combination with EDTA, to eradicate Staphylococcus epidermidis biofilms on silicone catheters. Biofouling. 2016 Aug;32(7):787-800. PMID:27351824 doi:10.1080/08927014.2016.1194401
- ↑ Grassi L, Maisetta G, Maccari G, Esin S, Batoni G. Analogs of the Frog-skin Antimicrobial Peptide Temporin 1Tb Exhibit a Wider Spectrum of Activity and a Stronger Antibiofilm Potential as Compared to the Parental Peptide. Front Chem. 2017 Apr 11;5:24. PMID:28443279 doi:10.3389/fchem.2017.00024
- ↑ Marcocci ME, Amatore D, Villa S, Casciaro B, Aimola P, Franci G, Grieco P, Galdiero M, Palamara AT, Mangoni ML, Nencioni L. The Amphibian Antimicrobial Peptide Temporin B Inhibits In Vitro Herpes Simplex Virus 1 Infection. Antimicrob Agents Chemother. 2018 Apr 26;62(5):e02367-17. PMID:29483113 doi:10.1128/AAC.02367-17
- ↑ Manzo G, Ferguson PM, Gustilo VB, Hind CK, Clifford M, Bui TT, Drake AF, Atkinson RA, Sutton JM, Batoni G, Lorenz CD, Phoenix DA, Mason AJ. Minor sequence modifications in temporin B cause drastic changes in antibacterial potency and selectivity by fundamentally altering membrane activity. Sci Rep. 2019 Feb 4;9(1):1385. doi: 10.1038/s41598-018-37630-3. PMID:30718667 doi:https://dx.doi.org/10.1038/s41598-018-37630-3
- ↑ Simmaco M, Mignogna G, Canofeni S, Miele R, Mangoni ML, Barra D. Temporins, antimicrobial peptides from the European red frog Rana temporaria. Eur J Biochem. 1996 Dec 15;242(3):788-92. PMID:9022710 doi:10.1111/j.1432-1033.1996.0788r.x
- ↑ Mangoni ML, Rinaldi AC, Di Giulio A, Mignogna G, Bozzi A, Barra D, Simmaco M. Structure-function relationships of temporins, small antimicrobial peptides from amphibian skin. Eur J Biochem. 2000 Mar;267(5):1447-54. PMID:10691983 doi:10.1046/j.1432-1327.2000.01143.x
- ↑ Rinaldi AC, Di Giulio A, Liberi M, Gualtieri G, Oratore A, Bozzi A, Schininà ME, Simmaco M. Effects of temporins on molecular dynamics and membrane permeabilization in lipid vesicles. J Pept Res. 2001 Sep;58(3):213-20. PMID:11576327 doi:10.1034/j.1399-3011.2001.00896.x
- ↑ Manzo G, Ferguson PM, Gustilo VB, Hind CK, Clifford M, Bui TT, Drake AF, Atkinson RA, Sutton JM, Batoni G, Lorenz CD, Phoenix DA, Mason AJ. Minor sequence modifications in temporin B cause drastic changes in antibacterial potency and selectivity by fundamentally altering membrane activity. Sci Rep. 2019 Feb 4;9(1):1385. doi: 10.1038/s41598-018-37630-3. PMID:30718667 doi:https://dx.doi.org/10.1038/s41598-018-37630-3
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