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The Science of Nature

, 105:56 | Cite as

A salamander’s toxic arsenal: review of skin poison diversity and function in true salamanders, genus Salamandra

  • Tim Lüddecke
  • Stefan Schulz
  • Sebastian Steinfartz
  • Miguel Vences
Review

Abstract

Terrestrial salamanders of the genus Salamandra represent one of the most prominent groups of amphibians. They are mainly distributed across Europe but also reach Northern Africa and the Near East. Members of the six currently accepted species have long been known to be poisonous; however, work on their toxins was mostly published in German language, and therefore, many nuances of these studies have remained hidden from the majority of herpetologists and toxinologists. Several Salamandra species are called fire salamanders due to their highly contrasted, black-yellow colouration which probably serves to deter predators, although thorough evidence for aposematism in Salamandra is still lacking. Salamandra skin toxins do not only represent a potent antipredator defence but may also have antimicrobial effects. A better understanding of this dual function of Salamandra skin secretions is of utmost importance in the face of the emergence of a fungal disease causing catastrophic declines of fire salamanders in Central Europe, caused by the fungus Batrachochytrium salamandrivorans. In this review, we summarize the knowledge on Salamandra toxins, providing a list of the compounds so far isolated from their secretion and focusing on the bioactivity of the major compounds in Salamandra secretions, the steroidal alkaloids. We identify priorities for future research, including a screening of co-occurrence of steroidal alkaloids and tetrodotoxins in salamandrids, chemical characterization of already identified novel steroidal compounds, elucidation of the presence and role of peptides and proteins in the secretion, and experimental in vitro and in vivo study of the interactions between bioactive compounds in Salamandra skin secretions and cutaneous fungal and bacterial pathogens.

Keywords

Amphibia Salamandridae Samandarine Samandarone Steroidal alkaloids Aposematism Batrachochytrium salamandrivorans 

Notes

Acknowledgements

Robin Schmidt and Janosch Knepper provided the material for the illustration of the figure. We are grateful to Kathleen Preißler for her fruitful discussions and input and to Pedro Galán for the bibliographic information.

References

  1. Andreone F, Clima V, De Michelis S (1999) On the ecology of Salamandra lanzai Nascetti, Andreone, Capula & Bullini, 1988. Number and movement of individuals, and influence of climate on activity in a population of the upper Po valley (Caudata: Salamandridae). Herpetozoa 12:3–10Google Scholar
  2. Anonymous (1529) Gart der Gesundheit, zu Latin ortus sanitatis. Von allerley Thieren Vögeln/Vischen oder Mözwundern und Edlem gestein/daruß gezogen von den natürlichen Meistern/was dem menschen zu seiner Gesundheit dienet/mit höchstem flesß durch sücht/korrigiert/und gebessert. StrassburgGoogle Scholar
  3. Balogová M, Uhrin M (2015) Sex-biased dorsal spot patterns in the fire salamander (Salamandra salamandra). Salamandra 51:12–18Google Scholar
  4. Balogová M, Kyselová M, Šafárik J, Uhrin M (2016) Changes in dorsal spot pattern in adult Salamandra salamandra (Linnaeus, 1758). Herpetozoa 28:167–171Google Scholar
  5. Bane V, Lehane M, Dikshit M, O’Riordan A, Furey A (2014) Tetrodotoxin: chemistry, toxicity, source, distribution and detection. Toxins (Basel) 6:693–755Google Scholar
  6. Bas S, Gasser F (1994) Polytypism of Salamandra salamandra (L.) in north-western Iberia. Mertensiella 4:41–74Google Scholar
  7. Becher JJ (1663) Parnassus medicinalis illustratus oder: Ein neues und dergestalt vormatzul noch nie gesehenes Thier-Kräuter- und Berg-Buch samt der Salernischen SchulGoogle Scholar
  8. Becker H (1986) Inhaltsstoffe von Feuer- und Alpensalamander. Pharm Unserer Zeit 15(4):97–106PubMedGoogle Scholar
  9. Benn M, Shaw R (1974) A Salamander Alkaloid Synthesis. Can J Chem 52(16):2936–2940Google Scholar
  10. Bettin C, Greven H (1986) Bacteria on the skin of Salamandra salamandra (L.) (Amphibia: Urodela) with notes on their possible significance. Zool Anz 216:267–270Google Scholar
  11. Beukema W, Nicieza AG, Lourenco A, Velo-Anton G (2016a) Colour polymorphism in Salamandra salamandra (Amphibia: Urodela), revealed by a lack of genetic and environmental differentiation between distinct phenotypes. J Zool Syst Evol Res 54:127–136.  https://doi.org/10.1111/jzs.12119 CrossRefGoogle Scholar
  12. Beukema W, Speybroeck J, Velo-Anton G (2016b) Salamandra. Curr Biol 26:696–697Google Scholar
  13. Bevins CL, Zasloff M (1990) Peptides from frog skin. Annu Rev Biochem 59:395–414PubMedGoogle Scholar
  14. Bletz MC, Loudon AH, Becker MH, Bell SC, Woodhams DC, Minbiole KP, Harris RN (2013) Mitigating amphibian chytridiomycosis with bioaugmentation: characteristics of effective probiotics and strategies for their selection and use. Ecol Lett 16:807–820PubMedGoogle Scholar
  15. Bletz MC, Goedbloed DJ, Sanchez E, Reinhardt T, Tebbe CC, Bhuju S, Geffers R, Jarek M, Vences M, Steinfartz S (2016) Amphibian gut microbiota shifts differentially in community structure but converges on habitat-specific predicted functions. Nat Commun 7:13699.  https://doi.org/10.1038/ncomms13699 CrossRefPubMedPubMedCentralGoogle Scholar
  16. Bogaerts S (2002) Farbkleidentwicklung bei einigen Feuersalamandern. Amphibia 1:4–10Google Scholar
  17. Böhme W (1979) Zum Höchstalter des Feuersalamanders “Salamandra salamandra” (L.), ein wiederentdecktes Dokument aus der Frühzeit der Terraristik (Amphibia: Caudata: Salamandridae). Salamandra 15:176–179Google Scholar
  18. Böhme W, Hartmann T, Fleck J, Schöttler T (2013) Miscellaneous notes on Oriental Fire Salamanders (Salamandra infraimmaculata Martens, 1885) (Lissamphibia: Urodela: Salamandridae). Russ J Herpetol 20:66–72Google Scholar
  19. Bonato L, Grossenbacher K (2000) On the distribution and chromatic differentiation of the alpine salamander Salamandra atra Laurenti, 1768, between Val Lagarina and Val Sugana (venetian Prealps): an updated review (Urodela: Salamandridae). Herpetozoa 13:171–180Google Scholar
  20. Bonato L, Steinfartz S (2005) Evolution of the melanistic colour in the alpine salamander Salamandra atra as revealed by a new subspecies from the Venetian Prealps. Ital J Zool 72:253–260Google Scholar
  21. Boulenger EG (1921) Experiments on colour-changes of the spotted salamanders (Salamandra maculosa), conducted in the society’s gardens. Proc Zool Soc Lond 91(1):99–102Google Scholar
  22. Bradley SG, Klika LJ (1981) A fatal poisoning from the Oregon rough-skinned newt (Taricha graulosa). J Am Med Assoc 246:247Google Scholar
  23. Brizzie R, Delfino G, Jantra S, Alvarez BB, Sever D (2001) The amphibian cutaneous glands: some aspects of their structure and adaptive role. In: Lymberakis P, Valakos E, Pafilis P, Mylonas M. Herpetologua Candiana, National Museum of Crete: CreteGoogle Scholar
  24. Brodie ED, Smatresk NJ (1990) The antipredator arsenal of fire salamanders: spraying of secretions from highly pressurized dorsal skin glands. Herpetologica 46:1–7Google Scholar
  25. Brown DD (1997) The role of thyroid hormone in zebrafish and axolotl development. Proc Natl Acad Sci U S A 94:13011–13016PubMedPubMedCentralGoogle Scholar
  26. Bucciarelli GM, Green DB, Shaffer HB, Kats LB (2016) Individual fluctuations in toxin levels affect breeding site fidelity in a chemically defended amphibian. Proc R Soc B Biol Sci 283(1831):20160468Google Scholar
  27. Buckley D, Alcobendas M, Garcia-Paris M, Wake MH (2007) Heterochrony, cannibalism, and the evolution of viviparity in Salamandra salamandra. Evol Dev 9:105–115PubMedGoogle Scholar
  28. Cardoso MH, Cobacho NB, Cherobim MD, Pinto MFS, dos Santos C, Maximiano MR, de Barros EG, Dias SC, Franco OL (2014) Insights into the antimicrobial activities of unusual antimicrobial peptide families from amphibian skin. Clin Toxicol 4:205.  https://doi.org/10.4172/2161-0495.1000205 CrossRefGoogle Scholar
  29. Carretero MA, Rosell C (1999) Salamandra salamandra (fire salamander). Predation. Herp Rev 30:161Google Scholar
  30. Caspers BA, Steinfartz S (2011) Preference for the other sex: olfactory sex recognition in terrestrial fire salamanders (Salamandra salamandra). Amphibia-Reptilia 32:503–508Google Scholar
  31. Caspers BA, Steinfartz S, Krause ET (2015) Larval deposition behaviour and maternal investment of females reflect differential habitat adaptation in a genetically diverging salamander population. Behav Ecol Sociobiol 69:407–413Google Scholar
  32. Dalbeck L, Düssel-Siebert H, Kerres A, Kirst K, Koch A, Lötters S, Ohlhoff D, Sabino-Pinto J, Preißler K, Schulte U, Schulz V, Steinfartz S, Veith M, Vences M, Wagner N, Wegge J (2018) Die Salamanderpest und ihr Erreger Batrachochytrium salamandrivorans (Bsal): aktueller Stand in Deutschland. Z Feldherpetol 25:1–22Google Scholar
  33. Daly JW (1998) Thirty years of discovering arthropod alkaloids in amphibian skin. J Nat Prod 61:162–172PubMedGoogle Scholar
  34. Daly JW, Spande TF (1986) Amphibian alkaloids: chemistry, pharmacology, and biology. In: Pelletier SW (ed) Alkaloids: chemical and biological perspectives. Wiley, New YorkGoogle Scholar
  35. Daly JW, Myers W, Whittaker N (1987) Further classification of skin alkaloids from neotropical poison frogs (Dendrobatidae), with a general survey of toxic/noxious substances in the amphibia. Toxicon 25:1023–1095PubMedGoogle Scholar
  36. Daly JW, Garrafo HM, Hall GFE, Cover JF Jr (1997) Absence of skin alkaloids in captive-raised Madagascan mantelline frogs (Mantella) and sequestration of dietary alkaloids. Toxicon 35:1131–1135PubMedGoogle Scholar
  37. Daly JW, Noimai N, Kongkathip B, Kongkathip N, Wilham JM, Garrafo HM, Kaneko T, Spande TF, Nimit Y, Nabhitabhata J, Chan-Ard T (2004) Biologically active substances from amphibians: preliminary studies on anurans from twenty-one genera of Thailand. Toxicon 44:805–815PubMedGoogle Scholar
  38. Daly JW, Spande TF, Garrafo HM (2005) Alkaloids from amphibian skin: a tabulation of over eight-hundred compounds. J Nat Prod 68:1556–1575PubMedGoogle Scholar
  39. Dean J, Aneshansley DJ, Edgerton HE, Eisner T (1990) Defensive spray of the bombardier beetle: a biological pulse jet. Science 248(4960):1219–1221PubMedGoogle Scholar
  40. Dethlefsen L, McFall-Ngai M, Relman DA (2007) An ecological and evolutionary perspective on human–microbe mutualism and disease. Nature 449:811–818PubMedGoogle Scholar
  41. Diamond G, Beckloff N, Weinberg A, Kirsch KO (2009) The roles of antimicrobial peptides in innate host defense. Curr Pharm Des 15:2377–2392PubMedPubMedCentralGoogle Scholar
  42. Dietrich N (1999) Jahreszyklus der Feuersalamander (Salamandra salamandra) des Neißetales – Landkreis Löbau-Zittau. Elaphe 7(2):62–65Google Scholar
  43. Dietrich N (2000) Der Schwarzspecht – ein Prädator unseres Feuersalamanders? Elaphe 8:65Google Scholar
  44. Duellman WE, Trueb L (1994) Biology of amphibians. JHU, BaltimoreGoogle Scholar
  45. Eom J, Jung YR, Park D (2009) F-series prostaglandin function as sex pheromones in the Korean salamander, Hynobius leechii. Comp Biochem Physiol A Mol Integrat Physiol 154:61–69Google Scholar
  46. Erjavec V, Lukanc B, Žel J (2017) Intoxication of a dog with alkaloids of the fire salamander. Med Weter 73:186–188Google Scholar
  47. Escoubas P (2006) Mass spectrometry in toxinology: a 21st-century technology for the study of biopolymers from venoms. Toxicon 47:609–613PubMedGoogle Scholar
  48. Esterly CO (1904) The structure and regeneration of the poison glands of Plethodon. Univ Calif Publ Zool 1:227–268Google Scholar
  49. Faust SE (1898) Beiträge zur Kenntniss des Samandarins. Arch Exp Pat Phyl 41:229–245Google Scholar
  50. Feldmann R, Klewen R (1981) Feuersalamander Salamandra salamandra terrestris Lacépède, 1788. In: Feldmann R (ed) Die Amphibien und Reptilien Westfalens. Abhandlungen aus dem Landes museum für Naturkunde Münster 43:30–44Google Scholar
  51. Fisher MC, Henk DA, Briggs CJ, Brownstein JS, Madoff LC, McCraw SL, Gurr SJ (2012) Emerging fungal threats to animal, plant and ecosystem health. Nature 484:186–194PubMedGoogle Scholar
  52. Fleck J (2005) Feuersalamanderbiotope in der Türkei. Amphibia 4(1):16–21Google Scholar
  53. Francis ETB (1934) The anatomy of the salamander. Clarendon, OxfordGoogle Scholar
  54. Francke H, Partch R (1966) The chemistry of samandarone model compounds. J Med Chem 9(4):643–644Google Scholar
  55. Freytag GE (1955) Feuersalamander und Alpensalamander. Wittenberg Lutherstadt (Ziemsen)Google Scholar
  56. Frisch K (1920) Über den Einfluss der Bodenfarbe auf die Fleckenzeichnung des Feuersalamanders. Biol Zentralblatt 40:390–414Google Scholar
  57. Fry BG, Roelants K, Champagne DE, Scheib H, Tyndall JD, King GF, Nevalainen TJ, Norman JA, Lewis RJ, Norton RS (2009) The toxicogenomic multiverse: convergent recruitment of proteins into animal venoms. Annu Rev Genomics Hum Genet 10:483–511PubMedGoogle Scholar
  58. Garcia-Paris M, Alcobendas M, Buckley D, Wake DB (2003) Dispersal of viviparity across contact zones in Iberian populations of fire salamanders (Salamandra) inferred from discordance of genetic and morphological traits. Evolution 57:129–143PubMedGoogle Scholar
  59. Gesner C (1669) Allgemeines Thier-Buch. Deutsche Übersetzung durch C. Forer, FrankfurtGoogle Scholar
  60. Geßner O (1926) Über Amphibiengifte. Ber Ges Beförderung ges Naturwiss (Mahrburg/Lahn) 61:138Google Scholar
  61. Geßner O (1928) Über die Wirkung der Krampfgifte Strychnin, Pikrotoxin und Samandarin. Arch Exp Pathol Pharmakol 129:261–270Google Scholar
  62. Geßner O (1932) Die Wirkung der Krampfgifte Strychnin, Pikrotoxin und Samandarin auf glattmuskelige Organe. Arch Exp Pathol Pharmakol 167:244–250Google Scholar
  63. Geßner O, Craemer K (1930) Zur Darstellung der Salamanderalkaloide aus dem Hautdrüsensekret von Salamandra maculosa. Arch Exp Pathol Pharmakol 152:229–237Google Scholar
  64. Geßner O, Esser W (1935a) Über die analeptische Wirkung des Salamanderalkaloides Samandarin. Arch Exp Pathol Pharmakol 178:755–759Google Scholar
  65. Geßner O, Esser W (1935b) Samandarin und eine Reihe von Umwandlungs- und Abbauprodukten des Samandarins. Arch Exp Pathol Pharmakol 179:639–645Google Scholar
  66. Geßner O, Möllenhoff P (1932) Zur Pharmakologie der Salamander-Alkaloide. Arch Exp Pathol Pharmakol 1671:638–653Google Scholar
  67. Geßner O, Urban G (1937) Weitere pharmakologische Untersuchungen zu Samandarin. Arch Exp Pathol Pharmakol 187:378–388Google Scholar
  68. Glaubrecht M (1991) Giftschleuder Feuersalamander. Kosmos 2:12Google Scholar
  69. Grant JB, Land B (2002) Transcutaneous amphibian stimulator (TAS): a device for the collection of amphibian skin secretions. Herpetol Rev 33:38–41Google Scholar
  70. Greven H (1994) Der Feuersalamander. Das Fabeltier und das Objekt moderner zoologischer Forschung. In: Kräubig J (ed) Lurchi- dem Feuersalamander auf der Spur. Galerie der Stadt Kornwestheim, KornwestheimGoogle Scholar
  71. Greven H (1997) Zur Naturgeschichte des Feuersalamanders in Mitteleuropa. In: Landschaftsverband Rheinland (ed) Der Salamander - ein gar fürchterliches Thier. Rheinland Verlag GmbH, KölnGoogle Scholar
  72. Grice EA, Segre JA (2013) The human microbiome: our second genome. Annu Rev Genomics Hum Genet 13:151–170Google Scholar
  73. Günter M (1926) Tötung durch Salamandergift. Lacerta 1:3–4Google Scholar
  74. Günther E (1998) Die Salamander des Tendi-Tals in Asturien/Nordspanien. Elaphe 6:96–97Google Scholar
  75. Habermehl G (1963a) Partialsynthese und absolute Konfiguration des Samandaridins. Chem Ber 96:840–844Google Scholar
  76. Habermehl G (1963b) Die Konstitution und Konfiguration des Samandaridins. Chem Ber 96:143–151Google Scholar
  77. Habermehl G (1964a) Cholesterin und Cholesterinester aus dem Hautdrüsensecret von Salamandra maculosa taeinata. Liebigs Ann Chem 680:104–107Google Scholar
  78. Habermehl G (1964b) O-Acetylsamandarin im Gift von Salamandra maculosa. Liebigs Ann Chem 679:164–167Google Scholar
  79. Habermehl G (1966) Die Konstitution des Samandenons. Chem Ber 99:1439–1442Google Scholar
  80. Habermehl G (1969) Chemistry and biochemistry of amphibian poisons. Naturwissenschaften 56(12):615–622PubMedGoogle Scholar
  81. Habermehl G (1994a) The biological relevance of Salamandra venom. Mertensiella 4:209–214Google Scholar
  82. Habermehl G (1994b) Gift-Tiere und ihre Waffen, 5 Aufl. Springer. BerlinGoogle Scholar
  83. Habermehl G (1995) Antimicrobial activity of amphibian venoms. Stud Nat Prod Chem 15:327–339Google Scholar
  84. Habermehl G, Göttlicher S (1965) Die Konstitution und Konfiguration des Cycloneosamandions. Chem Ber 98:1–10Google Scholar
  85. Habermehl G, Haaf G (1965) Cycloneosamandaridin, ein neues Nebenalkaloid aus Salamandra maculosa. Chem Ber 98:3001–3005Google Scholar
  86. Habermehl G, Haaf A (1968) Cholesterin als Vorstufe in der Biosynthese der Salamanderalkaloide. Chem Ber 101:198–200PubMedGoogle Scholar
  87. Habermehl G, Haaf A (1969) Konstitution und Synthese des Samanins. Liebigs Ann Chem 722:155–161Google Scholar
  88. Habermehl G, Preusser HJ (1969) Hemmung des Wachstums von Bakterien und Pilzen durch das Hautdrüsensekret von Salamandra maculosa. Z Naturforsch 24b:1599–1601Google Scholar
  89. Habermehl G, Preusser HJ (1970) Antimikrobielle Aktivität von Amphibien-Hautdrüsen-sekreten. Z Naturforsch 25b:1451–1452Google Scholar
  90. Habermehl G, Spiteller G (1967) Massenspektren der Salamander Alkaloide. Liebigs Ann Chem 706:213–222Google Scholar
  91. Habermehl G, Vogel G (1969) Samandinine, a minor alkaloid from Salamandra maculosa Laur. Toxicon 7:163–164PubMedGoogle Scholar
  92. Hanifin CT, Gilly WF (2015) Evolutionary history of a complex adaptation: tetrodotoxin resistance in salamanders. Evolution 69:232–244PubMedGoogle Scholar
  93. Hara S, Oka K (1967) A Total synthesis of samandarone. J Am Chem Soc 89:1041–1042PubMedGoogle Scholar
  94. Harris RN, Brucker RM, Walke JB, Becker MH, Schwantes CH, Flaherty DC, Lam BA, Woodhams DC, Briggs CJ, Vredenburg VT, Minbiole KP (2009) Skin microbes on frogs prevent morbidity and mortality caused by a lethal skin fungus. ISME J 3:818–824PubMedGoogle Scholar
  95. Harris RN, James TY, Lauer A, Simon MA, Patel A (2016) Amphibian pathogen Batrachochytrium dendrobatidis is inhibited by the cutaneous bacteria of amphibian species. Ecohealth 3:53–56Google Scholar
  96. Hayes AR, Piggott AM, Dalle K, Capon RJ (2009) Microbial biotransformation as a source of chemical diversity in cane toad steroid toxins. Bioorg Med Chem Lett 19:1790–1792PubMedGoogle Scholar
  97. Herbst C, Ascher F (1927) Beiträge zur Entwicklungsphysiologie der Färbung und Zeichnung der Tiere. III. Der Einfluss der Beleuchtung von unten auf das Farbkleid des Feuersalamanders. Wilhelm Roux’ Arch Entwickl Mech Org 112:1–59Google Scholar
  98. Horter M, Greven M (1981) Zur relativen Genießbarkeit juveniler Feuersalamander, Salamandra salamandra (L.) (Amphibia, Urodela). Amphibia-Reptilia 2:15–21Google Scholar
  99. Hostalka G (1984) Tod eines Jagdhundes durch Feuersalamander. Wild Hund 87(10):54–55Google Scholar
  100. Janssenswillen S, Vandebergh W, Treer D, Willaert B, Maex M, Van Bocxlaer I, Bossuyt F (2015) Origin and diversification of a salamander sex pheromone system. Mol Biol Evol 32:472–480PubMedGoogle Scholar
  101. Joly J (1968) Données écologiques sur la salamandre tachetée Salamandra salamandra (L.). Ann Sci Nat Zool Biol Anim 19:301–366Google Scholar
  102. Kabisch K, Belter H (1968) Das Verzehren von Amphibien durch Vögel. In: Abhandlungen und Berichte aus dem Staatlichen Museum für Tierkunde Dresden 29:191–227Google Scholar
  103. Kamalakkannan V, Salim AA, Capon RJ (2017) Microbiome-mediated biotransformation of cane toad bufagenins. J Nat Prod 80:2012–2017PubMedGoogle Scholar
  104. Kammerer P (1914a) Vererbung erzwungener Farbveränderungen. IV. Mitteilung: Das Farbkleid des Feuersalamanders (Salamandra maculosa Laurenti) in seiner Abhängigkeit von der Umwelt. Arch Entwickl Mech Org 36:4–193Google Scholar
  105. Kammerer P (1914b) Aufklärung zu vorstehenden Bemerkungen des Herrn Professor Baur. Arch Entwickl Mech Org 38:684Google Scholar
  106. Kershenbaum A, Blank L, Sinai I, Merilä J, Blaustein L, Templeton AR (2014) Landscape influences on dispersal behaviour: a theoretical model and empirical test using the fire salamander, Salamandra infraimmaculata. Oecologia 75:509–520.  https://doi.org/10.1007/s00442-014-2924-8 CrossRefGoogle Scholar
  107. Kikuyama S, Yamamoto K, Iwata T, Toyoda F (2002) Peptide and protein pheromones in amphibians. Comp Biochem Physiol B Biochem Molec Biol 132:69–74Google Scholar
  108. Koestler A (1971) The case of the midwife toad. Random House, New YorkGoogle Scholar
  109. König E, Bininda-Emmonds ORP, Shaw C (2015) The diversity and evolution of anuran skin peptides. Peptides 63:96–117PubMedGoogle Scholar
  110. Kozorog M (2003) Salamander brandy: “a psychedelic drink” between media myth and practice of home alcohol distillation in Slovenia. Anthropol East Eur Rev 21:63–71Google Scholar
  111. Kueneman J, Woodhams D, Van Treuren W, Archer W, Knight R, McKenzie V (2016) Inhibitory bacteria reduce fungi on early life stages of endangered Colorado boreal toads (Anaxyrus boreas). ISME J 10:934–944PubMedGoogle Scholar
  112. Linné C (1774). Vollständiges Natursystem. Deutsche Übersetzung durch P. C. S. Müller; 3. Theil: von den Amphibien. NürnbergGoogle Scholar
  113. Lu CX, Nan KJ, Lei Y (2008) Agents from amphibians with anticancer properties. Anti-Cancer Drugs 19:931–939PubMedGoogle Scholar
  114. Luiselli L, Anibaldi C, Capula M (1995) The diet of juvenile adders, Vipera berus, in an alpine habitat. Amphibia-Reptilia 16:404–407Google Scholar
  115. Luiselli L, Capula M, Shine R (1997) Food habits, growth rates, and reproductive biology of grass snakes, Natrix natrix (Colubridae) in the Italian alps. J Zool 241:371–380Google Scholar
  116. Malkmus R (2005a) Lautäußerungen bei Salamandra salamandra gallaica. Z Feldherpetol 12:131–132Google Scholar
  117. Malkmus R (2005b) Abwehrverhalten bei Salamandra salamandra gallaica und Salamandra salamandra crespoi. Z Feldherpetol 12:133–136Google Scholar
  118. Manenti R, Denoël M, Ficetola GF (2013) Foraging plasticity favours adaption to new habitats in fire salamanders. Anim Behav 86:375–382Google Scholar
  119. Manenti R, Pennati R, Ficetola GF (2015) Role of density and resource competition in determining aggressive behaviour in salamanders. J Zool 296:270–277Google Scholar
  120. Martel A, Spitzen-van der Sluijs A, Blooi M, Bert W, Ducatelle R, Fisher MC, Woeltjes A, Bosman W, Chiers K, Bossuyt F, Pasmans F (2013) Batrachochytrium salamandrivorans sp. nov. causes lethal chytridiomykosis in amphibians. Proc Natl Acad Sci U S A 110:15325–15329PubMedPubMedCentralGoogle Scholar
  121. McMenamin SK, Bain EJ, McCann AE, Patterson LB, Eom DS, Waller ZP, Hamill JV, Kuhlman JA, Eisen JS, Parichy DM (2014) Thyroid hormone-dependent adult pigment cell lineage and pattern in zebrafish. Science 345:1358–1361PubMedPubMedCentralGoogle Scholar
  122. Mebs D (2010) Gifttiere. Wissenschaftliche Verlagsgesellschaft, StuttgartGoogle Scholar
  123. Mebs D, Pogoda W (2005) Variability of alkaloids in the skin secretions of the European fire salamander (Salamandra salamandra terrestris). Toxicon 45:603–606PubMedGoogle Scholar
  124. Merabet K, Sanchez E, Dahmana A, Bogaerts S, Donaire D, Steinfartz S, Joger U, Vences M, Karar M, Moali A (2016) Phylogeographic relationships and shallow mitochondrial divergence of Algerian populations of Salamandra algira. Amphibia-Reptilia 37:1–8Google Scholar
  125. Michl E, Kaiser E (1963) Chemie und Biochemie der Amphibiengifte. Toxicon 1:175–228Google Scholar
  126. Muzinic J, Rasajski J (1992) On food and feeding habits of the white stork, Ciconia ciconia ciconia, on the Central Balkans. Ökol Vögel 14:211–223Google Scholar
  127. Nascetti G, Andreone F, Capula M, Bullini L (1988) A new Salamandra species from southwestern alps (Amphibia, Urodela, Salamandridae). Boll Mus Reg Sci Nat Torino 6:617–638Google Scholar
  128. Natchev N, Handschuh S, Lukanov S, Tzankov N, Naumov B, Werneburg I (2016) Contributions of the functional morphology of caudate skulls: kinetic and akinetic forms. PeerJ 4:e2392.  https://doi.org/10.7717/peerj.2392 CrossRefPubMedPubMedCentralGoogle Scholar
  129. Netolitzky F (1904) Untersuchungen über den giftigen Bestandteil des Alpensalamanders, Salamandra atra Laur. Arch Exp Pathol Pharmakol 51:118–129Google Scholar
  130. Obika M, Bagnara JT (1964) Pteridines as pigments in amphibians. Science 143:485–487PubMedGoogle Scholar
  131. Oka K, Hara S (1969) The synthesis of samane (desoxysamanine) and 17β-hydroxysamane. Tetrahedron Lett 10:1189–1191Google Scholar
  132. Oka K, Hara S (1977) Denial of the proposed structure of salamander alkaloid, cycloneosamandaridine. Total synthesis of cycloneosamandione and supposed cycloneosamandaridine. J Am Chem Soc 99:3859–3860PubMedGoogle Scholar
  133. Oka K, Ike Y, Hara S (1969a) The skeletal synthesis of early proposed cycloneosamandione | the synthesis of 19-homosteroids. Tetrahedron Lett 10:4543–4546Google Scholar
  134. Oka K, Ike Y, Hara S (1969b) The skeletal synthesis of early proposed cycloneosamandione || the synthesis of 19-retro-17β, 9-dihydroxy-3-aza-a-homo-5β-androstane. Tetrahedron Lett 10:4547–4550Google Scholar
  135. Otto F (1885) Wunderglaube und Wirklichkeit. In Rücksicht auf seltsame Erscheinungen der Tierwelt sowie unerklärliche Vorgänge im Menschenleben. Fabelhafte Gestalten des Wahns in Volksglauben, Sage und Dichtung. Verlag Otto Spemer, LeipzigGoogle Scholar
  136. Panagides N, Jackson TN, Ikonomopoulou MP, Arbuckle K, Pretzler R, Yang DC, Ali SA, Koludarov I, Dobson J, Sanker B, Asselin A, Santana RC, Hendrikx I, van der Ploeg H, Tai-A-Pin J, van den Bergh R, Kerkkamp HM, Vonk FJ, Naude A, Strydom MA, Jacobsz L, Dunstan N, Jaeger M, Hodgson WC, Miles J, Fry BG (2017) How the cobra got its flesh-eating venom: cytotoxicity as a defensive innovation and its co-evolution with hooding, aposematic marking, and spitting. Toxins (Basel) 9.  https://doi.org/10.3390/toxins9030103 PubMedCentralGoogle Scholar
  137. Park ST, Collingwood AM, St-Hilaire S, Sheridan PP (2014) Inhibition of Batrachochytrium dendrobatidis caused by bacteria isolated from the skin of boreal toads, Anaxyrus (Bufo) boreas boreas, from Grand Teton National Park, Wyoming, USA. Microbiol Insights 7:1–8PubMedPubMedCentralGoogle Scholar
  138. Paulitsch P (1984) Tod eines Jagdhundes durch Feuersalamander. Wild Hund 87:35Google Scholar
  139. Pezaro N, Rovelli V, Segev O, Templeton AR, Blaustein L (2017) Suspected rat predation oft he Near Eastern fire salamander (Salamandra infraimmaculata) by selective consumption of non toxic tissue. Zool Middle East 64:91–93Google Scholar
  140. Phisalix-Picot M (1900) Researches embryologiques, histologiques et physilogiques sur les glandes a venin de la Salamandre terrestre. Paris Mus Hist Nat Bull 6:294–300Google Scholar
  141. Preißler K, Pröhl H (2017) The effects of background coloration and dark spots on the risk of predation in poison frog models. Evol Ecol 31:683–694Google Scholar
  142. Preusser HJ, Habermehl G, Sablofski M, Schmall-Haury D (1975) Antimicrobial activity of alkaloids from amphibian venoms and effects on the ultrastructure of yeast cells. Toxicon 13:285–288PubMedGoogle Scholar
  143. Raaymakers C, Verbrugghe E, Hernot S, Hellebuyck T, Betti C, Peleman C, Claeys M, Bert W, Cavaliers V, Ballet S, Martel A, Pasmans F, Roelants K (2017) Antimicrobial peptides in frog poisons constitute a molecular toxin delivery system against predators. Nature. Communications 8:1495.  https://doi.org/10.1038/s41467-017-01710-1 CrossRefGoogle Scholar
  144. Raaymakers C, Verbrugghe E, Stijlemans B, Martel A, Pasmans F, Roelants K (2018) The anuran skin peptide bradykinin mediates its own absorption across epithelial barriers of the digestive tract. Peptides 103:84–89PubMedGoogle Scholar
  145. Reinhardt T, Steinfartz S, Paetzold A, Weitere M (2013) Linking the evolution of habitat choice to ecosystem functioning: direct and indirect effects of pond-reproducing fire salamanders on aquatic-terrestrial subsidies. Oecologia 173:281–291PubMedGoogle Scholar
  146. Riberon A, Miaud C, Grossenbacher K, Taberlet P (2001) Phylogeography of the alpine salamander, Salamandra atra (Salamandridae) and the influence of the Pleistocene climatic oscillations on population divergence. Mol Ecol 10:2555–2560PubMedGoogle Scholar
  147. Rivera X, Donaire-Barroso D, Arribas O (2014) Hipótesis sobre el origen y función del patrón de coloración y de las estrategias reproductivas en el género Salamandra Laurenti, 1768. Butll Soc Catalana Herpetol 21:75–92Google Scholar
  148. Rodriguez A, Poth D, Schulz S, Vences M (2011) Discovery of skin alkaloids in a miniaturized eleutherodactylid frog from Cuba. Biol Lett 7:414–418PubMedGoogle Scholar
  149. Rodríguez A, Burgon JD, Lyra M, Irisarri I, Baurain D, Blaustein L, Göçmen B, Künzel S, Mable BK, Nolte AW, Veith M, Steinfartz S, Elmer KR, Philippe H, Vences M (2017) Inferring the shallow phylogeny of true salamanders (Salamandra) by multiple phylogenomic approaches. Mol Phylogenet Evol 115:16–26PubMedGoogle Scholar
  150. Rodriguez C, Rollins-Smith L, Ibáñez R, Durant-Archibold AA, Gutiérrez M (2017) Toxins and pharmacologically active compounds from species of the family Bufonidae (Amphibia, Anura). J Ethnopharmacol 198:235–254PubMedGoogle Scholar
  151. Rollins-Smith LA (2009) The role of amphibian antimicrobial peptides in protection of amphibians from pathogens linked to global amphibian declines. Biochim Biophys Acta Biomembr 1788:1593–1599Google Scholar
  152. Rollins-Smith LA, Reinert LK, O’Leary CJ, Houston LE, Woodhams DC (2005) Antimicrobial peptide defenses in amphibian skin. Integr Comp Biol 45:137–142PubMedGoogle Scholar
  153. Roseghini M, Erspamer F, Severini C, Simmaco M (1989) Biogenic amines and active peptides in extracts of thirty-two European amphibian species. Comp Biochem Physiol 94:455–460Google Scholar
  154. Ruxton GD, Sherrat TN, Speed MP (2004) Avoiding attack. Oxford University Press, OxfordGoogle Scholar
  155. Sabino-Pinto J, Bletz M, Hendrix R, Perl RGB, Martel A, Pasmans F, Lötters S, Mutschmann F, Schmeller DS, Schmidt BR, Veith M, Wagner N, Vences M, Steinfartz S (2015) First detection of the emerging fungal pathogen Batrachochytrium salamandrivorans in Germany. Amphibia-Reptilia 36:411–416Google Scholar
  156. Sanchez E, Bletz MC, Duntsch L, Bhuju S, Geffers R, Jarek M, Dohrmann AB, Tebbe CC, Steinfartz S, Vences M (2017) Cutaneous bacterial communities of a poisonous salamander: a perspective from life stages, body parts and environmental conditions. Microb Ecol 73(2):455–465PubMedGoogle Scholar
  157. Sanchez E, Küpfer E, Goedbloed DJ, Nolte AW, Lüddecke T, Schulz S, Vences M, Steinfartz S (2018a) Morphological and transcriptomic analyses reveal three discrete primary stages of postembryonic development in the common fire salamander, Salamandra salamandra. J Exp Zool B Mol Dev Evol 330(2):96–108.PubMedGoogle Scholar
  158. Sanchez E, Gippner S, Vences M, Preißler K, Hermanski IJ, Caspers BA, Krause ET, Steinfartz S, Kastrup FW (2018b) Automatic quantification of colour proportions in dorsal black-and-yellow coloured amphibians, tested on the fire salamander (Salamandra salamandra). Herpetol Notes 11:73–76Google Scholar
  159. Saporito RA, Donnelly MA, Norton RA, Garraffo HM, Spande TF, Daly JW (2002) Oribatid mites: a major dietary source for alkaloids in poison frogs. Proc Natl Acad Sci U S A 104:8885–8890Google Scholar
  160. Sauer H, Weisbecker H (1994) Einheimische Schlangen als gelegentliche Verfolger des Feuersalamanders (Salamandra salamandra) – zwei Feldbeobachtungen. Nat Mus 124:349–350Google Scholar
  161. Schindler H, Frank (1961) Tiere in Pharmazie und Medizin. Hippokrates, StuttgartGoogle Scholar
  162. Schmidt BR, Feldmann R, Schaub M (2005) Demographic processes underlying growth and decline in Salamandra salamandra. Conserv Biol 19:1149–1156Google Scholar
  163. Schöpf C (1942) Die Konstitution des Samandarins. Liebigs Ann Chem 552:62–105Google Scholar
  164. Schöpf C (1961) Die Konstitution der Salamander-Alkaloide. Experientia 17:285–328Google Scholar
  165. Schöpf H (1992) Fabeltiere. VMA, WiesbadenGoogle Scholar
  166. Schöpf C, Braun W (1934) Über Samandarin, das Hauptalkaloid im Gift des Feuer- und Alpensalamanders. Liebigs Ann Chem 514:69–136Google Scholar
  167. Schöpf C, Koch K (1942) Über Samandaron und Samandaridin, Nebenalkaloide im Gift des Feuer- und Alpensalamanders. Liebigs Ann Chem 552:37–61Google Scholar
  168. Schöpf C, Möller OW (1960) Cycloneosamandion, ein neues Nebenalkaloid aus dem Feuersalamander (Salamandra maculosa Laur). Liebigs Ann Chem 633:127–156Google Scholar
  169. Schöpf C, Blödorn HK, Klein D, Seitz G (1950) Zur Konstitution des Samandarins. Chem Ber 83:372–390Google Scholar
  170. Schöpf C, Klein D, Hofmann E (1954) Die Darstellung von Dehydrierungs-Kohlenwasserstoffen aus Samandiol. Chem Ber 87:1638–1660Google Scholar
  171. Seidel U, Gerhardt P (2016) Die Gattung Salamandra. Edition Chimaira, Frankfurt am MainGoogle Scholar
  172. Servedio MR (2000) The effects of predator learning, forgetting, and recognition errors on the evolution of warning coloration. Evolution 54:751–763PubMedGoogle Scholar
  173. Shimizu Y (1976) Synthesis of samandarine-type alkaloids and analogues. J Org Chem 41:1930–1934Google Scholar
  174. Skelhorn J, Halpin CG, Rowe C (2016) Learning about aposematic prey. Behav Ecol 27(4):955–964Google Scholar
  175. Sousa LQ, Machado KD, Oliveira SF, Araújo LD, Monção-Filho ED, Melo-Cavalcante AA, Vieira-Júnior GM, Ferreira PM (2017) Bufadienolides from amphibians: a promising source of anticancer prototypes for radical innovation, apoptosis triggering and Na+/K+-ATPase inhibition. Toxicon 127:63–75PubMedGoogle Scholar
  176. Spitzen-van der Sluijs A, Martel A, Asselberghs J, Bales EK, Beukema W, Bletz MC, Dalbeck L, Goverse E, Kerres A, Kinet T, Kirst K, Laudelout A, Marin da Fonte LF, Nöllert A, Ohlhoff D, Sabino-Pinto J, Schmidt BR, Speybroeck J, Spikmans F, Steinfartz S, Veith M, Vences M, Wagner N, Pasmans F, Lötters S (2016) Expanding distribution of lethal amphibian fungus Batrachochytrium salamandrivorans in Europe. Emerg Infect Dis 22:1286–1288PubMedPubMedCentralGoogle Scholar
  177. Steinfartz S (2004) Salamandra- Feuer- und Alpensalamander. In: Böhme W (ed) Handbuch der Reptilien und Amphibien Europas (4:IIB). AULA, WiebelsheimGoogle Scholar
  178. Steinfartz S, Veith M, Tautz D (2000) Mitochondrial sequence analysis of Salamandra taxa suggests old splits of major lineages and postglacial recolonizations of Central Europe from distinct source populations of Salamandra salamandra. Mol Ecol 9:397–410PubMedGoogle Scholar
  179. Steinfartz S, Weitere M, Tautz D (2007) Tracing the first step to speciation—ecological and genetic differentiation of a salamander population in a small forest. Mol Ecol 16:4550–4561PubMedGoogle Scholar
  180. Stegen G, Pasmans F, Schmidt BR, Rouffaer LO, Van Praet S, Schaub M, Canessa S, Laudelout A, Kinet T, Adriaensen C, Haesebrouck F, Bert W, Bossuyt F, Martel A (2017) Drivers of salamander extirpation mediated by Batrachochytrium salamandrivorans. Nature 544(7650):353–356PubMedGoogle Scholar
  181. Stokes AN, Williams BL, French SS (2012) An improved competetive inhibition enzymatic immunoassay method for tetrodotoxin quantification. Biol Proced Online 14:3PubMedPubMedCentralGoogle Scholar
  182. Summers K, Clough ME (2001) The evolution of coloration and toxicity in the poison frog family (Dendrobatidae). Proc Natl Acad Sci U S A 98:6227–6232PubMedPubMedCentralGoogle Scholar
  183. Summers K, Speed MP, Blount JD, Stuckert AMM (2015) Are aposematic signals honest? Evol Biol 28:1583–1599Google Scholar
  184. Thiesmeier B (2004) Der Feuersalamander. Laurenti, BielefeldGoogle Scholar
  185. Trevisan P (1982) A new subspecies of alpine salamanders. Boll Zool 49:235–239Google Scholar
  186. Tsuruda K, Arakawa O, Kawatsu O, Hamano Y, Takatani T, Noguchi T (2002) Secretory glands of tetrodotoxin in the skin of the Japanese newt Cynops pyrrhogaster. Toxicon 40:131–136PubMedGoogle Scholar
  187. van Alphen JJM, Arntzen JW (2016) Paul Kammerer and the inheritance of acquired characteristics. Contrib Zool 85:457–470Google Scholar
  188. Van Bellegem SM, Papa R, Ortiz-Zuazaga H, Hendrickx F, Jiggins CD, McMillan WO, Counterman BA (2017) Patternize: an R package for quantifying colour pattern variation. Methods Ecol Evol 9:390–398Google Scholar
  189. Van Bocxlaer I, Maex M, Treer D, Janssenswillen S, Janssens R, Vandebergh W, Proost P, Bossuyt F (2016) Beyond sodefrin: evidence for a multi-component pheromone system in the model newt Cynops pyrrhogaster (Salamandridae). Sci Rep 6:21880PubMedPubMedCentralGoogle Scholar
  190. Velo-Anton G, Cordero-Rivera A (2011) Predation by invasive mammals on an insular viviparous population of Salamandra salamandra. Herpetol Notes 4:299–301Google Scholar
  191. Velo-Anton G, Zamudio KR, Cordero-Rivera A (2012) Genetic drift and rapid evolution of viviparity in insular fire salamanders (Salamandra salamandra). Heredity 108:410–418PubMedGoogle Scholar
  192. Vences M, Sanchez E, Hauswaldt SJ, Eikelmann D, Rodriguez A, Carranza S, Donaire D, Gehara M, Helfer V, Lötters S, Werner P, Schulz S, Steinfartz S (2014) Nuclear and mitochondrial multilocus phylogeny and survey of alkaloid content in true salamanders of the genus Salamandra (Salamandridae). Mol Phyl Evol 73:208–216Google Scholar
  193. von Byern J, Mebs D, Heiss E, Dicke U, Wetjen O, Bakkegard K, Grunwald I, Wolbank S, Mühleder S, Gugerell A, Fuchs H, Nuernberger S (2017) Salamanders on the bench—a biocompatibility study of salamander skin secretions in cell cultures. Toxicon 135:24–32Google Scholar
  194. Wang IJ, Shaffer HB (2008) Rapid color evolution in an aposematic species: a phylogenetic analysis of color variation in the strikingly polymorphic strawberry poison-dart frog. Evolution 62:2742–2759PubMedGoogle Scholar
  195. Werner C, Himstedt W (1984) Eye accomodation during prey capture behaviour in fire salamanders (Salamandra salamandra L.). Behav Brain Res 12:69–73PubMedGoogle Scholar
  196. Winter HG (1991) Färbung und Zeichnung. In: Klewen R (ed) Die Landsalamander Europas, Teil 1. Die Gattungen Salamandra und Mertensiella, 2 Aufl. Ziemsen, Wittenberg LutherstadtGoogle Scholar
  197. Wölfel E, Schöpf C, Weitz G, Habermehl G (1961) Die Konstitution und Konfiguration des Samandarins. Chem Ber 94:2361–2373Google Scholar
  198. Wood FW, Sollers BG, Dragoo GA, Dragoo JW (2002) Volatile components in defensive spray of the hooded skunk, Mephitis macroura. J Chem Ecol 28(9):1865–1870PubMedGoogle Scholar
  199. Woodhams DC, Brandt H, Baumgartner S, Kielgast J, Küpfer E, Tobler U, Davis LR, Schmidt BR, Bel C, Hodel S, Knight R, McKenzie V (2014) Interacting symbionts and immunity in the amphibian skin mucosome predicts disease risk and probiotic effectiveness. PLoS One 9:e96375.  https://doi.org/10.1371/journal.pone.0096375 CrossRefPubMedPubMedCentralGoogle Scholar
  200. Woodhams DC, LaBumbard BC, Barnhart KL, Becker MH, Bletz MC, Escobar LA, Flechas SV, Forman ME, Iannetta AA, Joyce MD, Rabemananjara F, Gratwicke B, Vences M, Minbiole KPC (2017) Prodigiosin, violacein, and volatile organic compounds produced by widespread cutaneous bacteria of amphibians can inhibit two Batrachochytrium fungal pathogens. Microbial Ecol 75:1049–1062.  https://doi.org/10.1007/s00248-017-1095-7 CrossRefGoogle Scholar
  201. Yotsu M, Iorizzi M, Yasumoto T (1990) Distribution of tetrodotoxin, 6-epitetrodotoxin and 11-deoxytetrodotoxin in newts. Toxicon 28:238–241PubMedGoogle Scholar
  202. Yotsu-Yamashita M, Mebs D, Kwet A, Schneider M (2007) Tetrodotoxin and its analogue 6-epitetrodotoxin in newts (Triturus spp.: Urodela, Salamandridae) from southern Germany. Toxicon 50:306–309PubMedGoogle Scholar
  203. Yotsu-Yamashita M, Toennes SW, Mebs D (2017) Tetrodotoxin in Asian newts (Salamandridae). Toxicon 134:14–17PubMedGoogle Scholar
  204. Zalesky S (1866) Über das Samandarin. Das Gift der Salamandra maculata. Med chem Untersuch Hoppe-Seyler 1:85–116Google Scholar

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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Zoological InstituteTechnische Universität BraunschweigBraunschweigGermany
  2. 2.Institute of Organic ChemistryTechnische Universität BraunschweigBraunschweigGermany

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