Defensin Explained

Symbol:Defensin
Defensin
Pfam Clan:CL0075
Opm Family:54
Opm Protein:6cs9

Defensins are small cysteine-rich cationic proteins across cellular life, including vertebrate[1] and invertebrate[2] animals, plants,[3] [4] and fungi.[5] They are host defense peptides, with members displaying either direct antimicrobial activity, immune signaling activities, or both. They are variously active against bacteria, fungi and many enveloped and nonenveloped viruses. They are typically 18-45 amino acids in length, with three or four highly conserved disulphide bonds.

In animals, they are produced by cells of the innate immune system and epithelial cells, whereas in plants and fungi they are produced by a wide variety of tissues. An organism usually produces many different defensins, some of which are stored inside the cells (e.g. in neutrophil granulocytes to kill phagocytosed bacteria), and others are secreted into the extracellular medium. For those that directly kill microbes, their mechanism of action varies from disruption of the microbial cell membrane to metabolic disruption.

Varieties

The name 'defensin' was coined in the mid-1980s, though the proteins have been called 'Cationic Antimicrobial Proteins,' 'Neutrophil peptides,' 'Gamma thionins' amongst others.[6]

Proteins called 'defensins' are not all evolutionarily related to one another.[7] Instead fall into two broad superfamilies, each of which contains multiple families.[8] One superfamily, the trans-defensins, contains the defensins found in humans and other vertebrates,[9] as well as some invertebrates.[10] [11] The other superfamily, cis-defensins, contains the defensins found in invertebrates, plants, and fungi.[12] [13] [14] The superfamilies and families are determined by the overall tertiary structure, and each family usually has a conserved pattern of disulphide bonds.[15] [16] All defensins form small and compact folded structures, typically with a high positive charge, that are highly stable due to the multiple disulphide bonds. In all families, the underlying genes responsible for defensin production are highly polymorphic.

Trans-defensins

Vertebrate defensins are primarily α-defensins and β-defensins. Some primates additionally have the much smaller θ-defensins. In general, both α- and β-defensins are encoded by two-exon genes, where the first exon encodes for a hydrophobic leader sequence (removed after translation) and the cysteine-rich sequence (the mature peptide). The disulfide linkages formed by the cysteines have been suggested to be essential for activities related to innate immunity in mammals, but are not necessarily required for antimicrobial activity.[17] [18] Theta defensins form a single beta-hairpin structure and represent a distinct group. Only alpha and beta-defensins are expressed in humans.[19]

Table of human defensins ! style="width:70px"
Type ! Gene Symbol Gene Name Protein Name Description - Defensin, alpha 1 Neutrophil defensin 1 Are expressed primarily in neutrophils as well as in NK cells and certain T-lymphocyte subsets. DEFA5 and DEFA6 are expressed in Paneth cells of the small intestine, where they may regulate and maintain microbial balance in the intestinal lumen. - Defensin, alpha 1B Defensin, alpha 1 - Defensin, alpha 3, neutrophil-specific Neutrophil defensin 3 - Defensin, alpha 4, corticostatin Neutrophil defensin 4 - Defensin, alpha 5, Paneth cell-specific Defensin-5 - Defensin, alpha 6, Paneth cell-specific Defensin-6 - Defensin, beta 1 Beta-defensin 1 Are the most widely distributed, being secreted by leukocytes and epithelial cells of many kinds. For example, they can be found on the tongue, skin, cornea, salivary glands, kidneys, esophagus, and respiratory tract. It has been suggested (but also challenged) that some of the pathology of cystic fibrosis arises from the inhibition of β-defensin activity on the epithelial surfaces of the lungs and trachea due to higher salt content. - Defensin, beta 2 Beta-defensin 2
DEFB3Defensin, beta 3Beta-defensin 3 - Defensin, beta 103B Beta-defensin 103 - ... ... ... - Defensin, beta 106A Beta-defensin 106A - DEFB106B Defensin, beta 106B Beta-defensin 106B -Defensin, beta 107A Beta-defensin 107 -Defensin, beta 110Beta-defensin 110 -... ...... -Defensin, beta 136Beta-defensin 136 - Defensin, theta 1 pseudogene not expressed in humans Are rare, and thus far have been found only in the leukocytes of the rhesus macaque[20] and the olive baboon, Papio anubis, the gene coding for it is corrupted in humans and other primates.[21] [22]
Although the most well-studied defensins are from vertebrates, a family of trans-defensins called 's' are found in molluscs, arthropods and lancelets.

Cis-defensins

Arthropod defensins are the best-characterised defensins from invertebrates (especially those from insects).[23] Other invertebrates known to produce defensins from this protein superfamily include molluscs, annelids and cnidaria.[24]

Plant defensins were discovered in 1990 and have subsequently been found in most plant tissues with antimicrobial activities, with both antifungal and antibacterial examples.[25] They have been identified in all major groups of vascular plants, but not in ferns, mosses or algae.

Fungal defensins were first identified in 2005.[26] Studied examples mainly have anti-bacterial activities and have been found in both main divisions of fungi (Ascomycota and Basidiomycota), as well as in the more basal groups of Zygomycota and Glomeromycota.[27]

Bacterial defensins have also been identified, but are by far the least studied. They include variants with only four cysteines, whereas defensins from eukaryote defensins almost all have six or eight.[28]

Related defensin-like proteins

In addition to the defensins involved in host defence, there are a number of related Defensin-Like Peptides (DLPs) that have evolved to have other activities.

Toxins

There appear to have been multiple evolutionary recruitments of defensins to be toxin proteins used in the venoms of animals;[29] they act via a completely different mechanism to their antimicrobial relatives, from binding directly to ion channels to disrupting nerve signals. Examples include the crotamine toxin in snake venom,[30] many scorpion toxins,[31] some sea anemone toxins,[9] and one of the toxins in platypus venom.[29] Indeed, an insect defensin has been experimentally converted into a toxin by deletion of a small loop that otherwise sterically hindered interactions with the ion channels.[32]

Signalling

In vertebrates, some α- and β-defensins are involved in signalling between the innate immune and adaptive immune systems.[33] [34] In plants, a specialised family of DLPs is involved in signalling to detect if self-pollination has occurred and induce self-incompatibility to prevent inbreeding.[35]

Enzyme inhibitors

Some antimicrobial defensins also have enzyme inhibitory activity, and some DLPs function primarily as enzyme inhibitors, acting as antifeedants (discouraging animals from eating them).[36] [37] [38]

Function

In immature marsupials, because their immune system is underdeveloped at the time of birth, defensins play a major role in defense against pathogens. They are produced in the milk of the mother as well as by the young marsupial in question.

In human breast milk, defensins play a central role in neonate immunity.[39]

The human genome contains theta-defensin genes, but they have a premature stop codon, hampering their expression. An artificial human theta-defensin, retrocyclin, was created by 'fixing' the pseudogene, and it was shown to be effective against HIV[40] and other viruses, including herpes simplex virus and influenza A. They act primarily by preventing these viruses from entering their target cells.

Also interesting is the effect of alpha-defensins on the exotoxin produced by anthrax (Bacillus anthracis). Chun Kim et al. showed how anthrax, which produces a metalloprotease lethal factor (LF) protein to target MAPKK, is vulnerable to human neutrophil protein-1 (HNP-1). This group showed HNP-1 to behave as a reversible noncompetitive inhibitor of LF.[41]

They have generally been considered to contribute to mucosal health; however, it is possible that these peptides can be considered biological factors that can be upregulated by bioactive compounds present in human breast milk. In this sense, the intestinal production of antimicrobial peptides as hBD2 and hBD4 by trefoil from milk might play an important role on neonate colonization, thereby enhancing the immune response of newborns against pathogens with which they may come in contact.[42]

Pathology

The alpha defensin peptides are increased in chronic inflammatory conditions.

Alpha defensin are increased in several cancers, including colorectal cancer.[43]

An imbalance of defensins in the skin may contribute to acne.[44]

A reduction of ileal defensins may predispose to Crohn's disease.[45] [46]

In one small study, a significant increase in alpha defensin levels was detected in T cell lysates of schizophrenia patients; in discordant twin pairs, unaffected twins also had an increase, although not as high as that of their ill siblings. The authors suggested that alpha-defensin levels might prove a useful marker for schizophrenia risk.[47]

Defensins are found in the human skin during inflammatory conditions like psoriasis[48] and also during wound healing.

Applications

Defensins

At present, the widespread spread of antibiotic resistance requires the search and development of new antimicrobial drugs. From this point of view, defensins (as well as antimicrobial peptides in general) are of great interest. It was shown that defensins have pronounced antibacterial activity against a wide range of pathogens.[49] In addition, defensins can enhance the effectiveness of conventional antibiotics.

Defensin-mimetics

Defensin mimetics, also called host defense peptide (HDP) mimetics, are completely synthetic, non-peptide, small molecule structures that mimic defensins in structure and activity.[50] Similar molecules, such as brilacidin, are being developed as antibiotics,[51] anti-inflammatories for oral mucositis,[52] and antifungals, especially for candidiasis.[53] [54] [55]

See also

External links

Notes and References

  1. Hazlett L, Wu M . 2234617 . Defensins in innate immunity . Cell and Tissue Research . 343 . 1 . 175–88 . January 2011 . 20730446 . 10.1007/s00441-010-1022-4 .
  2. Tassanakajon A, Somboonwiwat K, Amparyup P . Sequence diversity and evolution of antimicrobial peptides in invertebrates . Developmental and Comparative Immunology . 48 . 2 . 324–41 . February 2015 . 24950415 . 10.1016/j.dci.2014.05.020 . Specific immunity in invertebrates .
  3. Thomma BP, Cammue BP, Thevissen K . 19356421 . Plant defensins . Planta . 216 . 2 . 193–202 . December 2002 . 12447532 . 10.1007/s00425-002-0902-6 . 2002Plant.216..193T .
  4. Sathoff AE, Samac DA . Antibacterial Activity of Plant Defensins . Molecular Plant-Microbe Interactions . 32 . 5 . 507–514 . May 2019 . 30501455 . 10.1094/mpmi-08-18-0229-cr . free .
  5. Wu J, Gao B, Zhu S . The fungal defensin family enlarged . Pharmaceuticals . 7 . 8 . 866–80 . August 2014 . 25230677 . 4165938 . 10.3390/ph7080866 . free .
  6. Lehrer RI . 8774156 . Primate defensins . Nature Reviews. Microbiology . 2 . 9 . 727–38 . September 2004 . 15372083 . 10.1038/nrmicro976 .
  7. Shafee TM, Lay FT, Hulett MD, Anderson MA . The Defensins Consist of Two Independent, Convergent Protein Superfamilies . Molecular Biology and Evolution . 33 . 9 . 2345–56 . September 2016 . 27297472 . 10.1093/molbev/msw106 . free .
  8. Shafee TM, Lay FT, Phan TK, Anderson MA, Hulett MD . 24741736 . Convergent evolution of defensin sequence, structure and function . Cellular and Molecular Life Sciences . 74 . 4 . 663–682 . February 2017 . 27557668 . 10.1007/s00018-016-2344-5 . 11107677 .
  9. Mitchell ML, Shafee T, Papenfuss AT, Norton RS . Evolution of cnidarian trans-defensins: Sequence, structure and exploration of chemical space . Proteins . 87 . 7 . 551–560 . July 2019 . 30811678 . 10.1002/prot.25679 . 73469576 . free . 11343/285595 . free .
  10. Zhu S, Gao B . Evolutionary origin of β-defensins . Developmental and Comparative Immunology . 39 . 1–2 . 79–84 . 2013 . 22369779 . 10.1016/j.dci.2012.02.011 .
  11. Montero-Alejo V, Corzo G, Porro-Suardíaz J, Pardo-Ruiz Z, Perera E, Rodríguez-Viera L, Sánchez-Díaz G, Hernández-Rodríguez EW, Álvarez C, Peigneur S, Tytgat J, Perdomo-Morales R . 19734223 . Panusin represents a new family of β-defensin-like peptides in invertebrates . Developmental and Comparative Immunology . 67 . 310–321 . February 2017 . 27616720 . 10.1016/j.dci.2016.09.002 .
  12. Dias RD, Franco OL . Cysteine-stabilized αβ defensins: From a common fold to antibacterial activity . Peptides . 72 . 64–72 . October 2015 . 25929172 . 10.1016/j.peptides.2015.04.017 . Festschrift to highlight the career of Abba J. Kastin as a founding editor, researcher, and educator in the peptide field . 17846143 . free .
  13. Shafee T, Anderson MA . 51968286 . A quantitative map of protein sequence space for the cis-defensin superfamily . Bioinformatics . 35 . 5 . 743–752 . March 2019 . 30102339 . 10.1093/bioinformatics/bty697 .
  14. Zhu S . Discovery of six families of fungal defensin-like peptides provides insights into origin and evolution of the CSalphabeta defensins . Molecular Immunology . 45 . 3 . 828–38 . February 2008 . 17675235 . 10.1016/j.molimm.2007.06.354 .
  15. Book: Hollox. Edward J.. Abujaber. Razan . Evolution and Diversity of Defensins in Vertebrates. 2017. Evolutionary Biology: Self/Nonself Evolution, Species and Complex Traits Evolution, Methods and Concepts. 27–50. Pontarotti. Pierre. Springer International Publishing. en. 10.1007/978-3-319-61569-1_2. 978-3-319-61569-1.
  16. Wang YP, Lai R . [Insect antimicrobial peptides: structures, properties and gene regulation] ]. Dong Wu Xue Yan Jiu = Zoological Research . 31 . 1 . 27–34 . February 2010 . 20446450 . 10.3724/sp.j.1141.2010.01027 . 4692675 . free . 1807/64439 . free .
  17. Varkey J, Singh S, Nagaraj R . 21104756 . Antibacterial activity of linear peptides spanning the carboxy-terminal beta-sheet domain of arthropod defensins . Peptides . 27 . 11 . 2614–23 . November 2006 . 16914230 . 10.1016/j.peptides.2006.06.010 .
  18. Varkey J, Nagaraj R . Antibacterial activity of human neutrophil defensin HNP-1 analogs without cysteines . Antimicrobial Agents and Chemotherapy . 49 . 11 . 4561–6 . November 2005 . 16251296 . 1280114 . 10.1128/AAC.49.11.4561-4566.2005 .
  19. Dhople V, Krukemeyer A, Ramamoorthy A . The human beta-defensin-3, an antibacterial peptide with multiple biological functions . Biochimica et Biophysica Acta (BBA) - Biomembranes . 1758 . 9 . 1499–512 . September 2006 . 16978580 . 10.1016/j.bbamem.2006.07.007 . 36461159 .
  20. Tran D, Tran P, Roberts K, Osapay G, Schaal J, Ouellette A, Selsted ME . Microbicidal properties and cytocidal selectivity of rhesus macaque theta defensins . Antimicrobial Agents and Chemotherapy . 52 . 3 . 944–53 . March 2008 . 18160518 . 2258523 . 10.1128/AAC.01090-07 .
  21. Angie Eva . Garcia . Michael . Selsted . March 2008 . Olive baboon θ-defensins . 10.1096/fasebj.22.1_supplement.673.11 . The FASEB Journal . 22 . 1 Suppl . 673.11 . free. 89807163 .
  22. Garcia AE, Osapay G, Tran PA, Yuan J, Selsted ME . Isolation, synthesis, and antimicrobial activities of naturally occurring theta-defensin isoforms from baboon leukocytes . Infection and Immunity . 76 . 12 . 5883–91 . December 2008 . 18852242 . 2583559 . 10.1128/IAI.01100-08 .
  23. Koehbach J . Structure-Activity Relationships of Insect Defensins . English . Frontiers in Chemistry . 5 . 45 . 2017 . 28748179 . 5506212 . 10.3389/fchem.2017.00045 . 2017FrCh....5...45K . free .
  24. Greco S, Gerdol M, Edomi P, Pallavicini A . Molecular Diversity of Mytilin-Like Defense Peptides in Mytilidae (Mollusca, Bivalvia) . Antibiotics . 9 . 1 . 37 . January 2020 . 31963793 . 10.3390/antibiotics9010037 . 7168163 . free .
  25. Parisi K, Shafee TM, Quimbar P, van der Weerden NL, Bleackley MR, Anderson MA . The evolution, function and mechanisms of action for plant defensins . Seminars in Cell & Developmental Biology . 88 . 107–118 . April 2019 . 29432955 . 10.1016/j.semcdb.2018.02.004 . 3543741 .
  26. Mygind PH, Fischer RL, Schnorr KM, Hansen MT, Sönksen CP, Ludvigsen S, Raventós D, Buskov S, Christensen B, De Maria L, Taboureau O, Yaver D, Elvig-Jørgensen SG, Sørensen MV, Christensen BE, Kjaerulff S, Frimodt-Moller N, Lehrer RI, Zasloff M, Kristensen HH . Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus . Nature . 437 . 7061 . 975–80 . October 2005 . 16222292 . 10.1038/nature04051 . 2005Natur.437..975M . 4423851 .
  27. Wu J, Gao B, Zhu S . The fungal defensin family enlarged . Pharmaceuticals . 7 . 8 . 866–80 . August 2014 . 25230677 . 4165938 . 10.3390/ph7080866 . free .
  28. Dash TS, Shafee T, Harvey PJ, Zhang C, Peigneur S, Deuis JR, Vetter I, Tytgat J, Anderson MA, Craik DJ, Durek T, Undheim EA . A Centipede Toxin Family Defines an Ancient Class of CSαβ Defensins . Structure . 27 . 2 . 315–326.e7 . February 2019 . 30554841 . 10.1016/j.str.2018.10.022 . free .
  29. Whittington CM, Papenfuss AT, Bansal P, Torres AM, Wong ES, Deakin JE, Graves T, Alsop A, Schatzkamer K, Kremitzki C, Ponting CP, Temple-Smith P, Warren WC, Kuchel PW, Belov K . Defensins and the convergent evolution of platypus and reptile venom genes . Genome Research . 18 . 6 . 986–94 . June 2008 . 18463304 . 2413166 . 10.1101/gr.7149808 .
  30. Batista da Cunha D, Pupo Silvestrini AV, Gomes da Silva AC, Maria de Paula Estevam D, Pollettini FL, de Oliveira Navarro J, Alves AA, Remédio Zeni Beretta AL, Annichino Bizzacchi JM, Pereira LC, Mazzi MV . 205440053 . Mechanistic insights into functional characteristics of native crotamine . Toxicon . 146 . 1–12 . May 2018 . 29574214 . 10.1016/j.toxicon.2018.03.007 . 11449/170828 . free .
  31. Possani LD, Becerril B, Delepierre M, Tytgat J . Scorpion toxins specific for Na+-channels . European Journal of Biochemistry . 264 . 2 . 287–300 . September 1999 . 10491073 . 10.1046/j.1432-1327.1999.00625.x . free .
  32. Zhu S, Peigneur S, Gao B, Umetsu Y, Ohki S, Tytgat J . Experimental conversion of a defensin into a neurotoxin: implications for origin of toxic function . Molecular Biology and Evolution . 31 . 3 . 546–59 . March 2014 . 24425781 . 10.1093/molbev/msu038 . free .
  33. Petrov V, Funderburg N, Weinberg A, Sieg S . Human β defensin-3 induces chemokines from monocytes and macrophages: diminished activity in cells from HIV-infected persons . Immunology . 140 . 4 . 413–20 . December 2013 . 23829433 . 3839645 . 10.1111/imm.12148 .
  34. Semple F, Dorin JR . β-Defensins: multifunctional modulators of infection, inflammation and more? . Journal of Innate Immunity . 4 . 4 . 337–48 . 2012 . 22441423 . 6784047 . 10.1159/000336619 .
  35. Book: Fobis-Loisy I, Ivanov R, Gaude T . The S-LOCUS CYSTEINE-RICH PROTEIN (SCR): A Small Peptide with a High Impact on the Evolution of Flowering Plants . 2012. 77–92. Springer Berlin Heidelberg. 978-3-642-27602-6 . 10.1007/978-3-642-27603-3_5. Plant Signaling Peptides. 16. Signaling and Communication in Plants.
  36. News: Porcine pancreatic alpha-amylase in complex with helianthamide, a novel proteinaceous inhibitor. Williams LK, Brayer GD . 2015-11-25. 10.2210/pdb4x0n/pdb.
  37. News: Minimized NMR structure of ATT, an Arabidopsis trypsin/chymotrypsin inhibitor. Zhao Q, Chae YK, Markley JL . 2003-01-07 . 10.2210/pdb1jxc/pdb.
  38. Pelegrini PB, Lay FT, Murad AM, Anderson MA, Franco OL . Novel insights on the mechanism of action of alpha-amylase inhibitors from the plant defensin family . Proteins . 73 . 3 . 719–29 . November 2008 . 18498107 . 10.1002/prot.22086 . 28378146 .
  39. Barrera GJ, Sanchez G, Gonzalez JE . Trefoil factor 3 isolated from human breast milk downregulates cytokines (IL8 and IL6) and promotes human beta defensin (hBD2 and hBD4) expression in intestinal epithelial cells HT-29 . Bosnian Journal of Basic Medical Sciences . 12 . 4 . 256–64 . November 2012 . 23198942 . 4362502 . 10.17305/bjbms.2012.2448 .
  40. Münk C, Wei G, Yang OO, Waring AJ, Wang W, Hong T, Lehrer RI, Landau NR, Cole AM . The theta-defensin, retrocyclin, inhibits HIV-1 entry . AIDS Research and Human Retroviruses . 19 . 10 . 875–81 . October 2003 . 14585219 . 10.1089/088922203322493049 .
  41. Kim C, Gajendran N, Mittrücker HW, Weiwad M, Song YH, Hurwitz R, Wilmanns M, Fischer G, Kaufmann SH . Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences . Proceedings of the National Academy of Sciences of the United States of America . 102 . 13 . 4830–5 . March 2005 . 15772169 . 555714 . 10.1073/pnas.0500508102 . 2005PNAS..102.4830K . free .
  42. Barrera GJ, Tortolero GS . Trefoil factor 3 (TFF3) from human breast milk activates PAR-2 receptors, of the intestinal epithelial cells HT-29, regulating cytokines and defensins . Bratislavske Lekarske Listy . 117 . 6 . 332–9 . 2016 . 27546365 . 10.4149/bll_2016_066 . free .
  43. Albrethsen J, Bøgebo R, Gammeltoft S, Olsen J, Winther B, Raskov H . Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours: a biomarker study . BMC Cancer . 5 . 8 . January 2005 . 15656915 . 548152 . 10.1186/1471-2407-5-8 . free .
  44. Philpott MP . Defensins and acne . Molecular Immunology . 40 . 7 . 457–62 . November 2003 . 14568392 . 10.1016/S0161-5890(03)00154-8 .
  45. Genomics & Genetics Weekly . Researchers discover a possible cause of chronic inflammations of Crohn Disease . August 11, 2006 . 72 .
  46. Wehkamp J, Salzman NH, Porter E, Nuding S, Weichenthal M, Petras RE, Shen B, Schaeffeler E, Schwab M, Linzmeier R, Feathers RW, Chu H, Lima H, Fellermann K, Ganz T, Stange EF, Bevins CL . Reduced Paneth cell alpha-defensins in ileal Crohn's disease . Proceedings of the National Academy of Sciences of the United States of America . 102 . 50 . 18129–34 . December 2005 . 16330776 . 1306791 . 10.1073/pnas.0505256102 . 2005PNAS..10218129W . free .
  47. Craddock RM, Huang JT, Jackson E, Harris N, Torrey EF, Herberth M, Bahn S . Increased alpha-defensins as a blood marker for schizophrenia susceptibility . Molecular & Cellular Proteomics . 7 . 7 . 1204–13 . July 2008 . 18349140 . 10.1074/mcp.M700459-MCP200 . 35381828 . free .
  48. Harder J, Bartels J, Christophers E, Schroder JM . Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic . The Journal of Biological Chemistry . 276 . 8 . 5707–13 . February 2001 . 11085990 . 10.1074/jbc.M008557200 . 9516726 . free .
  49. Bolatchiev A . 2020-11-25. Antibacterial activity of human defensins against Staphylococcus aureus and Escherichia coli . PeerJ . 8 . e10455 . 10.7717/peerj.10455 . 33304659. 7698690 . free .
  50. Press release: PolyMedix. 2008-05-09. Business Wire
  51. News: PMX-30063 The First And Only Defensin Mimetic Systemic Antibiotic Drug In Human Clinical Trials . 2008 .
  52. Web site: Brilacidin-OM page. Cellceutix. 2015-03-02. https://web.archive.org/web/20150207051957/http://cellceutix.com/brilacidin-om/#sthash.SDIn67NC.dpbs. 2015-02-07. dead.
  53. Web site: Candidiasis. Cellceutix. 2015-03-02. https://web.archive.org/web/20150207073612/http://cellceutix.com/candidiasis/#sthash.f36Zt7H7.dpbs. 2015-02-07. dead.
  54. A Novel Therapeutic For Invasive Candiasis . Fox Chase Chemical Diversity Center . Grantome. Diamond . Gill . Scott . Richard .
  55. Ryan LK, Freeman KB, Masso-Silva JA, Falkovsky K, Aloyouny A, Markowitz K, Hise AG, Fatahzadeh M, Scott RW, Diamond G . Activity of potent and selective host defense peptide mimetics in mouse models of oral candidiasis . Antimicrobial Agents and Chemotherapy . 58 . 7 . 3820–7 . July 2014 . 24752272 . 4068575 . 10.1128/AAC.02649-13 .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Defensin".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.