Researchers may have an antidote for the deadliest jellyfish sting on Earth

first_img By Bethany AugliereApr. 30, 2019 , 11:00 AM Click to view the privacy policy. Required fields are indicated by an asterisk (*) Researchers may have an antidote for the deadliest jellyfish sting on Earth Sign up for our daily newsletter Get more great content like this delivered right to you! Country Country * Afghanistan Aland Islands Albania Algeria Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia, Plurinational State of Bonaire, Sint Eustatius and Saba Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Congo, the Democratic Republic of the Cook Islands Costa Rica Cote d’Ivoire Croatia Cuba Curaçao Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands (Malvinas) Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and McDonald Islands Holy See (Vatican City State) Honduras Hungary Iceland India Indonesia Iran, Islamic Republic of Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Korea, Democratic People’s Republic of Korea, Republic of Kuwait Kyrgyzstan Lao People’s Democratic Republic Latvia Lebanon Lesotho Liberia Libyan Arab Jamahiriya Liechtenstein Lithuania Luxembourg Macao Macedonia, the former Yugoslav Republic of Madagascar Malawi Malaysia Maldives Mali Malta Martinique Mauritania Mauritius Mayotte Mexico Moldova, Republic of Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Norway Oman Pakistan Palestine Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Qatar Reunion Romania Russian Federation Rwanda Saint Barthélemy Saint Helena, Ascension and Tristan da Cunha Saint Kitts and Nevis Saint Lucia Saint Martin (French part) Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Sint Maarten (Dutch part) Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Islands South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syrian Arab Republic Taiwan Tajikistan Tanzania, United Republic of Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates United Kingdom United States Uruguay Uzbekistan Vanuatu Venezuela, Bolivarian Republic of Vietnam Virgin Islands, British Wallis and Futuna Western Sahara Yemen Zambia Zimbabwe Kelvin Aitken/VWPics via AP Images center_img Email Chironex fleckeri is one of 51 known species of box jellyfish, whose venom is among the world’s deadliest. The sting of a box jellyfish can kill a person in minutes. But scientists have long been at pains to figure out the secret of its fast-acting venom, which can also cause severe agony, inflammation, and heart attacks. A new study may have the answer—and a potential antidote.The finding is “tour de force,” says Angel Yanagihara, a biochemist who studies jellyfish venom at the University of Hawaii in Honolulu, but who wasn’t involved with the work.Up to 40 people die each year from box jellies, according to available figures. But that number is vastly underreported, Yanagihara says. “People die and there is no trace in the public records.” In the Philippines alone, she estimates some 500 people die from box jelly stings each year. And as the ocean warms—and as the range and number of box jellyfish rises—problematic encounters will likely increase. But to date, no one knows how the box jelly’s venom targets and enters human cells. Previous work on their venom has shown that pore-forming proteins, called porins, destroy red blood cells and damage cell membranes, potentially resulting in pain and death. Yet, more components could be responsible.In the new study, geneticist Greg Neely of the University of Sydney in Australia and colleagues collected live Chironex fleckeri, the species of box jellyfish responsible for most human deaths, from coastal waters off of the Northern Territory of Australia. They soaked the tentacles in seawater, recovered the capsules that contain the stinging cells, and then broke them with tiny glass beads to release the venom, which they freeze-dried.Next, the scientists generated a pool of millions of myeloid cells, each of which was missing one of 19,050 genes. (Because the cells, derived from a leukemia patient, have just one set of chromosomes, they are often used for genetic screening tests.) Then, the scientists added the freeze-dried venom and looked for cells that didn’t die. If a cell survived, they sequenced its DNA to identify which gene was missing—and thus, which made proteins that were likely targeted by the venom.The screen suggested four genes involved in cholesterol production were the venom’s targets, they report today in Nature Communications. So, Neely’s team tested the ability of existing cholesterol-targeting drugs to see whether they could also block the venom. Two drugs, MbCD and HPbCD, prevented the venom from killing the human myeloid cells and rupturing mouse red blood cells in a well-plate for up to 15 minutes after exposure, Neely says. The team then gave HPbCD, considered safe for humans, to mice that had been injected with C. fleckeri venom. For 15 minutes, the drug blocked pain, tissue death, and scarring.Neely says he was surprised that he and his colleagues could block the venom’s action with a single drug, given that the venom itself is composed of more than 250 proteins. “It’s kind of lucky that it worked out.” The researchers hypothesize that because HPbCD works by pulling cholesterol out of the cell membrane, jellyfish venom may rely on cholesterol to gain an entryway into the cell. However, Neely says, MbCD may also act directly on the venom to neutralize it.Yanagihara, who has developed a topical cream to help treat box jellyfish stings, says she’s skeptical that the cholesterol drug treatment will be sufficient by itself, because it has so far only been used against processed venom—not stings from live animals, thought to be more potent. “The next step would be to ground truth these findings by live tentacle sting tests on live animals.”Neely says that because their venom caused all the symptoms of a typical sting in the mice, he believes the results will translate to the real world. And he’s already looking forward to the next step: testing whether the cholesterol drugs protect the heart in live animals. Eventually, he hopes to bring the potential antidote to human clinical trials.If those should work, the antidote has much promise, says Cheryl Ames, a marine biologist from the Smithsonian Institution’s National Museum of Natural History in Washington, D.C., who was not involved in the study. “It’s very cool stuff, [and] I’m pumped.”last_img

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