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Transgenic human skin bacteria to produce repellents?

February 1, 2010 - 08:07 -- Bart G.J. Knols

Ninety years ago it was discovered that mosquitoes track us down at night by responding to the smell we as humans produce. Since then, many studies have focused on identifying the nature of the chemicals we produce with the aim to use them to lure mosquitoes to trapping devices, thereby interrupting bloodfeeding and thus transmission of diseases like malaria. But why is there still no trap available for use in the developing world where malaria hits hardest?

A major complication is the fact that the search for active chemicals is like searching for a needle in a haystack. Humans produce several hundred organic compounds (from the skin and exhaled breath) and it has proven difficult to identify the ones that really matter. In the 1960s, research commenced in Gainesville Florida to identify attractants for the yellow fever mosquito Aedes aegypti. Since the late 1980s research on anopheline olfaction became fashionable as a novel means to interrupt disease transmission through trap development. Methods to determine if a mosquito detects a chemical were developed (electrophysiology) and high through-put systems followed in recent years. Although there is still no trap, two recent publications report hope that in due course this may change.

 

First, Niels Verhulst and colleagues reported an intriguing development. Although the possible role of skin biota (skin bacteria) has been published before, he was the first to succeed in attracting Africa’s main malaria vector, Anopheles gambiae sensu stricto, to the scent produced by skin bacteria only. In other words, he succeeded in attracting this mosquito, which has a strong preference for biting humans, to bacteria that were isolated from the human foot and cultivated on growth medium (agar). Without the presence of a human. Think of it, it is not us that lure mosquitoes…. It is the microflora on our skin. What can we do with this?

 

1)   Develop probiotics that compete with ‘attractant-producing’ bacteria (such as Staphylococcus epidermidis that produces attractants);

2)   Develop ‘soaps’ that selectively remove the bacteria that produce attractants. These would not be repellents, they would be called ‘making-you-less-attractiveants’;

3)   Develop bait systems (e.g. broths) that are based on bacteria and attract mosquitoes;

4)   Develop transgenic bacteria that produce repellents on our skin and mask the production of attractants….

 

Second, Fredros Okumu and colleagues claimed to have found a blend of compounds for Anopheles arabiensis that is 3-5 times more attractive as a human being. That’s really something. Perhaps we are closer to having a blend, that can be used in a trap in or near every hut in Tanzania, than we thought.

 

Key is that Okumu’s research was undertaken in a semi-field system (a large outdoor screened cage), which facilitated high through-put of compounds or blends thereof. Much more emphasis on testing of compounds in field settings should bring us closer to a trap over the next few years. The paper in PLoS ONE then details the results of an experimental hut study that is pretty convincing.

 

But there is more that needs done. We need a cheap source of carbon dioxide as well. And here Wolfgang Schmied has come up with a great idea – using locally available resources – to use Coca Cola bottles, with water, yeast, and sugar. The result: carbon dioxide. The results have not been published yet.

 

Next, we need a very cheap trap that can hopefully run free of power or utilise a renewable energy source (solar panel). Goal: the trap should cost less than 1 dollar. Alas, this is an idea we submitted to Gates, but they did not like it...

 

Combining the studies above should, however, lead to enough creative ideas to tackle the long-standing dream of mass trapping malaria vectors.

 

Give us your idea...

Comments

Fredros Okumu's picture
Submitted by Fredros Okumu on

It is obvious that development and adoption of new tools for malaria control has been dreadfully slow in the past years. the success of vector control tools such as ITNs and IRS have partly contributed to the decline in mechanisms for prospecting for the necessary alternative tools. Nevertheless, there are now real opportunities for development of tools such as odor baited traps which will be suitable for use in most malaria endemic countries. We have recently shown that it is possibly to create artificial lures that not only mimic humans but that can actually actract more mosquitoes than humans. If incoporated in simple and cheap traps produced at community level, and if such traps can be optimally located in areas where mosquitoes are most abundant, such lures represent real opportunities for developing new tools to complement existing methods such as nets and IRS. Another interesting finding recently has been that by luring host seeking mosquitoes to predetermined stations, the mosquitoes may be contaminated with larvicides and used to horizontally disperse small quantities of such larvicides to their most productive larval breeding habitats

Mark Benedict's picture
Submitted by Mark Benedict on

Mr. Okumu highlights a great idea that deserves development. The combination of attractants and IGR transport to breeding sites could be very powerful since larval control will be difficult to accomplish unless we let mosquitoes do the work of finding sites. This is exactly the kind of idea that donors who are serious about creating novel interventions should welcome - and support.

Bart G.J. Knols's picture
Submitted by Bart G.J. Knols on

This idea was published last year in PNAS (http://www.ncbi.nlm.nih.gov/pubmed/19561295?itool=EntrezSystem2.PEntrez....) where Aedes aegypti carried pyriproxyfen that was applied indoors to breeding sites and killed their own offspring. Also this was not the first investigation of this kind. In Charles Apperson's lab it was first demonstrated (back in 2003) that females can be 'contaminated' and carry lethal compoounds to breeding sites (see http://www.ncbi.nlm.nih.gov/pubmed/12823839?itool=EntrezSystem2.PEntrez....)

Submitted by Ricardo Ataide on

Thanks for posting this.

It is a field full of possibilities and that would probably deserve a lot more attention that it actually gets. I speak for myself also. Although concerned with the methods that can be used to prevent or decrease infections (ITNs, Indoor spraying, habitat control, etc.) I would not remember to focus on a simple, still, ingenious idea like "smell-traps".

I guess some of the questions are: how many traps would be needed, how long would they last, how would they be replaced, who would do the replacement, who would cover the costs of replacement...

Still, nothing that cannot be solved, i'm sure.

Ricardo Ataíde

Niels Verhulst's picture
Submitted by Niels Verhulst on

It has already been shown in 1953 by Shelley et al. that bacteria play an important role in the production of body odour. More recent studies confirmed that skin bacteria determine the human odour profile. Although the possible role of skin bacteria in the host seeking behaviour of mosquitoes was published before, I am still surprised that it gets little attention when scientists study the host seeking behaviour of mosquitoes. Many fundamental questions remain unanswered.
- Do mosquitoes prefer a certain body site because of skin bacteria?
- Is there adaptation of the skin microbiota in malaria areas?
- If a plasmodium infection makes people more attractive to mosquitoes is this because of a change in skin bacteria?
- is host preference regulated by skin bacteria of the different hosts
Bart also mentioned the use of bacteria on the skin or in a trap.
In a trap is possible, for sure and it would be cheap, but the design and release will be important.
I think people are not willing to use transgenic bacteria on their skin, but it has already been shown in studies on foot odour that specific odour producing bacterial enzymes can be blocked.
If think the skin bacteria are a good example of how a better understanding of the host seeking behaviour of mosquitoes can lead to creative ideas to tackle the malaria problem.

Niels Verhulst Wageningen University

Submitted by Guest (not verified) on

Dear sir,
I am impressed by your latest findings that link malaria with smelly socks. I am the author of a newly published book entitled: Medicinal use of fresh Air & Water published by Amazon at http://www.amazon.com/dp/1466221380. It is a practical guide by which people can learn to optimize intake of fresh air and drinking water to stimulate natural healing of the body or boost natural immunity to diseases. I am a science graduate who has been conducting medical research over the last nine years. I started my research program in 2002 when I invented a new method for maximizing intake of fresh air as a form of medication called aerotherapy, which has proven to be highly effective in preventing or fighting off malaria. I discovered a link between having regular optimal exposure of the body to fresh air and enjoying higher level of protection against malaria. I spent over seven years without suffering from malaria since I adopted aerotherapy in 2002 as opposed to my past record of having an average of one malaria attack per annum prior to 2002. Meanwhile people in my immediate surrounding such as room mates continued contracting malaria over that seven year period of my immunity. I also discovered the scientific significance of drinking adequate water in protecting a human body against malaria. Two out of three trials that I conducted this year in my clinical case study have successfully proven that a human body can fend off malaria fever by ensuring sufficient intake of drinking water and cool fresh air. Some scientists had ever argued (hypothesized) that a human body can naturally heal itself from malaria provided the symptom of fever could be kept at bay. These solutions keep fever at bay while giving the body ample time to naturally heal itself or buy more time say some weeks/months for one to access affordable medical services. My discoveries have not been widely publicized or reported due to my lack of sponsors. My related research reports can be found on my website/blog. Your kind response will be highly appreciated.
Yours faithfully,

Eporu Ronald
Author/Founder,
Aero-medical Sciences,
Computer Point (opposite Kakira mosque), Jinja, Uganda
Telephone: +256 0712 066386
http://aerotherapy.wordpress.com