title: Intraspecific variations in Conus geographus defence-evoked venom and estimation of the human lethal dose.
abstract: Conus geographus is the most dangerous cone snail species known, with reported human fatality rates as high as 65%. Crude venom gland extracts have been used to determine animal LD50 and to aid the isolation of several potent paralytic toxins. However, not only is the composition of injected venoms known to differ significantly from that in dissected venom glands, but also to vary according to predatory or defensive stimuli. Therefore, to study the venom that is directly relevant to human envenomation, the defense-evoked venom of several specimens of C. geographus was collected and analyzed by standard LC-MS methods. The molecular composition of individual defense-evoked venom showed significant intraspecific variations, but a core of paralytic conotoxins including α-GI, α-GII, μ-GIIIA, ω-GVIA and ω-GVIIA was always present in large amounts, consistent with the symptomology and high fatality rate in humans. Differences between injected and dissected venoms obtained from the same specimen were also evident. Interestingly, an apparent linear correlation between the dry weight/volume of injected venom and the size of the shell allowed extrapolation to a human lethal dose (0.038-0.029 mg/kg) from an historic fatal case of C. geographus envenomation, which may help in the management of future victims.
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247, Université Montpellier 2 - CNRS, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France; Institute for Molecular Bioscience, The University of Queensland, 4072 Queensland, Australia. Electronic address: Sebastien.Dutertre@univ-montp2.fr.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Dutertre
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, 4072 Queensland, Australia.
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Jin
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, 4072 Queensland, Australia.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Alewood
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, 4072 Queensland, Australia.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lewis
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D052078:Conus Snail / Q000737:chemistry* / Q000145:classification; D006801:Humans; D040901:Proteomics; D013045:Species Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D020866:omega-Conotoxin GVIA / Q000737:chemistry / Q000633:toxicity*
chemical_list: D020866:omega-Conotoxin GVIA
keywords: Cone snails; Conotoxin; Lethal dose; Milking; Venom