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Super fungus bites mozzies

October 2019

The mosquito has a reputation for being "the most dangerous animal in the world" credited with killing "one million people a year" (Bates). 

Actually, it's unlikely any mosquito has ever killed anyone, but several very nasty human pathogens have seized the opportunity of hitching a ride from person to person inside biting mosquitoes.

Mosquito-born disease isn't just a developing world problem. Fifty-two Scots were diagnosed with malaria in 2018 after travelling abroad. One of them died.


 
By 'biting mosquito' is meant the egg-carrying females of 6% of mozzie species (out of about 3,500 known species) which need 'blood meals' to develop their eggs and which require, prefer or just happen to alight on a convenient body containing human blood which happens to be infected, before carrying on to infect the involuntary donor of their next blood meal. 

Apart from this momentary carnivorous interlude on the part of a tiny proportion of the global mosquito population, the insects mostly feed on plant nectar.  They're important pollinators and a food for birds, bats, fish and frogs.  In other words, they form a significant part of ecosystems worldwide.  One science writer argues that, by making the tropical rainforests so inhospitable to humans, "Nothing has done more to delay (the catastrophic destruction of the rainforests) over the past 10,000 years than the mosquito". 

Since chemical insecticides were invented, attempts have been on-going to decimate mosquito populations with treated bed-nets and room walls, and spraying the stagnant water which supports the larval stage. However, mozzies breed fast (their life-cycle is about three weeks) and can evolve quickly: insecticide resistance is an increasing problem. 

Genetic engineers have had their attention on exterminating mosquitoes for some time.  Oxitec's GM mosquitoes with a gene drive to spread the self-destruct trait through the entire mozzie population have had the most press [1].  The latest GM venture hijacks a natural fungal pathogen of insects to deliver potent insecticides. 

These new super-insecticides are based on those found in the venom of the Australian funnel-web spider, described by one author as a "scare machine". 

Spiders produce an estimated 5-20 million 'peptide' toxins: these are tiny protein-like molecules which can kill by interfering with nerve function.  Most peptide toxins act specifically on the spiders' prey, and are then consumed by the same spider.  The funnel-web spider doesn't of course hunt down people, but by an evolutionary accident some of the peptides in its repertoire can kill a human within 15 minutes of being bitten by a spider they've chanced to disturb. 

GM yeast fermentation-based spider and scorpion venom insecticides were approved for crop spraying by the US Environmental Protection Agency (EPA) in 2016. Now trials are underway using GM venom-producing fungi which infect mosquitoes. 

The fungus used is a mosquito pathogen which feeds off and kills its victims.  This takes a few days (it's not good pathogenic practice to wipe out your food supply too quickly) and, although the insects are sickened and take fewer and smaller blood meals and produce fewer eggs, there's still time for the mosquito to continue reproducing, biting and spreading disease.  The GM venom-producing versions, however, kill their hosts faster than they can reproduce, and do so at a lower level of infection by the fungus. 

In a "neat ... super-exciting study" using a simulated village and controlled environment, the GM fungus collapsed the mosquito population completely in just two generations. 

We are assured that the chosen GM venom isn't one which makes humans drop dead, isn't harmful to beneficial species such as honeybees, and is engineered to switch on only inside the mosquito.  The GM fungal spores can easily be deployed inside houses by mixing them with widely available sesame oil and using this to coat easily obtainable black sheets on which biting mozzies like to rest after their blood meal. 

For maximum lethal outcome, the fungus can be engineered to produce multiple neurotoxins.  The most effective GM fungus so far identified generated both a spider and a scorpion GM venom. 

OUR COMMENT

This latest mosquito extermination scheme involves an intimate interaction between three factors. 

A fungus which is ubiquitous in soil and which has close relatives able to infect a wide range of insects.  It has proven to be "very malleable, you can genetically engineer them very easily" (its DNA seems very open to change).  This fungus will be forced by artificial DNA to do something which is not in its own interests, i.e. to kill its food/host quickly.

The wide specific host range isn't a chance situation: the fungi can detect when they are in contact with the 'right' insect species. Adapting to accept an alternative 'right' insect species can't be too big a step for it.


An artificial neurotoxic peptide, a small molecule which has many close toxic relatives, not normally present in nature except in spider food.  This will be spread by infected mosquitoes wherever they fly and die. 

A species of mosquito which bites people and animals and injects saliva.  It's also known to marshal its immune system defences on detecting the presence of an attacking fungus, and to be able to alter its reproductive cycle to beat the debilitation caused by the fungus. 

This sounds like a three-tiered melting-pot of evolutionary pressures in organisms with an excellent intrinsic scope for evolutionary change: the fungi can easily evolve to 'improve' their relationship to their host or to spread to other hosts; the artificial neurotoxin could easily evolve into something much more toxic; the mosquito could easily evolve to survive the toxin long enough to reproduce.   The outcome could be mosquitoes with a bite like funnel-web scare-machine.

HYPE ALERTS! 

The same toxin that's in the mosquito-busting fungus has been approved by the EPA as an insecticidal crop spray. It's promoted as a 'natural' non-chemical insecticide, even although it's produced by GM yeast in factories. By the same sleight of hand, the fungus is also a 'natural' mozzie pathogen, even in GM, spider-impersonating, form.

Oft repeated in the media is that the GM fungus is "not harmful to beneficial species such as bees". However, the only readily available supporting details seem to be that honey-bees exposed the GM fungal spores didn't die during a two-week observation and didn't become infected. No one seems to have asked what might happen when the GM spores are ferried back to the hive.

The specificity claim seems unlikely:
  • The fungus doesn't only live in mosquitoes: its' a ubiquitous soil-inhabiting fungus with plenty of scope for adapting to other insect species. No one seems to have asked what effect the venomous GM fungus might have in the soil.
  • The engineered genetic switch designed to turn on the venom production only in a mosquito might behave differently under environmental stress.
  • Notably, the venom itself kills insects of very different types, for example moths as targeted by the EPA-approved spray and mosquitoes as targeted by the GM fungus.
  • The fungus and its venom won't just disappear when the mosquito dies: this could mean more evolutionary pressure in the field.
The illusions of safety and specificity are, of course, a necessary precedent for the biotech industry's bigger aim of using GM pathogens for the control of other mosquito- and insect-transmitted diseases of people and crops.

WHAT YOU CAN DO

Any time you read about or hear the above claims in the media, point out to the editor that he or she is spreading pro-GM propaganda (bad journalism).

Note on alternative approaches
Since an ecosystem mozzie-gap will certainly be filled by something else, possibly worse, you might be wondering by now if it wouldn't be safer to target the disease rather than the innocent and otherwise useful carrier. Community-based trials are underway of 'Wolbachia' non-GM bacteria which naturally boosts the mosquito immune-system so that they are no longer able to host, or spread, key viral diseases, such as Zika, dengue fever, chikungunya or yellow fever. Glasgow University has recently developed a drug which kills the malarial parasite at three stages in its complex life cycle and prevents its sexual development.


Background 

SOURCES: 
  • Brian Lovett, et al., 2019, Transgenic Metarhizium rapidly kills mosquitoes in a malaria-endemic region of Burkina Faso, Science 364 
  • Ernst-Jan Scholte, et al., 2005, Infection of the malaria mosquito Anopheles gambiae with the entomopathogenic fungus Metarhizium anisopliae reduces blood feeding and fecundity, Journal of Invertebrate Pathology 91 
  • Abeer M. Alkhaibari, et al., July 2016, Metarhizium brunneum Blastopore Pathogenesis in Aedes aegypti Larvae: Attack on several Fronts Accelerates Mortality, PLOS Pathogens  
  • Shannon Verhagen, World's deadliest spider: the funnel-web, Australian Geographic, 13.02.17 
  • New drug 'kills malaria at all three life stage', Metro, 30.08.19 
  • Metro Bites, 31.07.19 
  • Luke Taylor, Biting back: mosquitoes used to fight diseases they spread, i, 13.07.19 
  • Etienne Gilgo, et al., June 2017, Improved efficacy of an arthropod toxin expressing fungus against insecticide-resistant malaria-vector mosquitoes, Nature Scientific Reports 7 
  • Transgenic fungus Rapidly Killed Malaria Mosquitoes in West African Study, University of Maryland News, 29.05.19 
  • Transgenic fungus rapidly killed malaria mosquitoes in West African study, www.sciencedaily.com, 30.05.19 
  • Gretchen Vogel, Fungus with a venom gene could be new mosquito killer, www.sciencemag.org, 30.05.19 
  • James Gallagher, GM fungus rapidly kills 99% of malaria mosquitoes, study suggests, www.bbc.co.uk, 31.05.19 
  • Mosquito-killing Fungi Engineered with Spider and Scorpion Toxins Could Help Fight Malaria, University of Maryland, College of Computer, Mathematical and Natural Sciences, 13.06.17 
  • Carolina Brunner-Mendoza, et al., October 2018, A review on the genus Metarhiziumas an entomopathogenic microbial biocontrol agent with emphasis on its use and utility in Mexico, Biocontrol Science & Technology 29 
  • Weiguo Fang, et al., December 2014, Construction of a Hypervirulant and Specific Mycoinsecticide for Locust Control, Nature Scientific Reports Applied Microbiology Molecular Engineering 4 
  • Matt Hickman, Is spider venom the ultimate natural pesticide? Mother Nature Network, 9.05.16 
  • Josh Hrala, Scientists Are Using One of The World's Deadliest Venoms as a Safer Insecticide, www.sciencealert.com, 14.05.16 
  • Applications of Spider Venom, www.chm.bris.ac.uk 
  • Allan Adamson, Genetically Modified Fungus Kills 99 Percent of Malaria Mosquitoes In Just 45 Days, www.techtimes.com, 31.05.19 
  • Claire Bates, Would it be wrong to eradicate mosquitoes​?, www.bbc.co.uk, 28.01.16 
  • Cameron Webb, Who, What, and Where Do Mosquitoes Bite?, Entomology Today, 8.06.16
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