Abstract

Chironex fleckeri (Australian box jellyfish) stings can cause acute cardiovascular collapse and death. We developed methods to recover venom with high specific activity, and evaluated the effects of both total venom and constituent porins at doses equivalent to lethal envenomation. Marked potassium release occurred within 5 min and hemolysis within 20 min in human red blood cells (RBC) exposed to venom or purified venom porin. Electron microscopy revealed abundant ∼12-nm transmembrane pores in RBC exposed to purified venom porins. C57BL/6 mice injected with venom showed rapid decline in ejection fraction with progression to electromechanical dissociation and electrocardiographic findings consistent with acute hyperkalemia. Recognizing that porin assembly can be inhibited by zinc, we found that zinc gluconate inhibited potassium efflux from RBC exposed to total venom or purified porin, and prolonged survival time in mice following venom injection. These findings suggest that hyperkalemia is the critical event following Chironex fleckeri envenomation and that rapid administration of zinc could be life saving in human sting victims.

Highlights

  • The class Cubozoa comprises two families (Carybdeidae and Chirodropidae) [1]

  • While expanding geographic ranges have been reported for many jellyfish species, possibly as a result of changes in ocean currents, over-fishing and warmer ocean temperatures related to climate change [5], the apparent expansion of the range of cubozoan species may be the result of more careful medical reporting of lethal attacks, as well as more recreational activities in existing habitats

  • We show that the potassium leak caused by the cubozoan porin is the likely cause of hemodynamic collapse, and that treatment with a safe, readily available zinc compound significantly prolongs survival of mice

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Summary

Introduction

The class Cubozoa (phylum Cnidaria) comprises two families (Carybdeidae and Chirodropidae) [1]. The most notorious of the latter is the large (.1 kilogram) Australian box jellyfish (Chironex fleckeri), which displays up to 60 two-meter long, ribbon-like tentacles and inhabits coastal mangroves over a broad and potentially expanding geographic range, spanning 40u latitude from Australia to Vietnam [2]. Life-threatening Chironex fleckeri envenomations occur each year, typically from November to May, in North Queensland, Australia [3,4]. Since the report of the first cubozoan hemolytic porin from Alatina moseri (previously reported as Carybdea alata) [11], all cubozoans investigated have been found to contain close homologs of this porin; two isoforms are present in Chironex fleckeri venom (MW 43 and 45 kDa) [12]. The venom has been recognized to create pores in myocytic membranes [13]

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