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Mosquitoes are Drawn to Your Skin Bacteria

There’s only two more days left in 2011, so time for my final paper a month post for 2011!

Like with the paper I blogged for last month, this month’s paper (from open access journal PLoS ONE) is yet again about the impact on our health of the bacteria which have decided to call our bodies home. But, instead of the bacteria living in our gut, this month is about the bacteria which live on our skin.

Its been known that the bacteria that live on our skin help give us our particular odors. So, the researchers wondered if the mosquitos responsible for passing malaria (Anopheles) were more or less drawn to different individuals based on the scent that our skin-borne bacteria impart upon us (also, for the record, before you freak out about bacteria on your skin, remember that like the bacteria in your gut, the bacteria on your skin are natural and play a key role in maintaining the health of your skin).

Looking at 48 individuals, they noticed a huge variation in terms of attractiveness to Anopheles mosquitos (measured by seeing how much mosquitos prefer to fly towards a chamber with a particular individual’s skin extract versus a control) which they were able to trace to two things. The first is the amount of bacteria on your skin. As shown in Figure 2 below, is that the more bacteria that you have on your skin (the higher your “log bacterial density”), the more attractive you seem to be to mosquitos (the higher your mean relative attractiveness).

Figure 2

The second thing they noticed was that the type of bacteria also seemed to be correlated with attractiveness to mosquitos. Using DNA sequencing technology, they were able to get a mini-census of what sort of bacteria were present on the skins of the different patients. Sadly, they didn’t show any pretty figures for the analysis they conducted on two common types of bacteria (Staphylococcus and Pseudomonas), but, to quote from the paper:

The abundance of Staphylococcus spp. was 2.62 times higher in the HA [Highly Attractive to mosquitoes] group than in the PA [Poorly Attractive to mosquitoes] group and the abundance of Pseudomonas spp. 3.11 times higher in the PA group than in the HA group.

Using further genetic analyses, they were also able to show a number of other types of bacteria that were correlated with one or the other.

So, what did I think? While I think there’s a lot of interesting data here, I think the story could’ve been tighter. First and foremost, for obvious reasons, correlation does not mean causation. This was not a true controlled experiment – we don’t know for a fact if more/specific types of bacteria cause mosquitos to be drawn to them or if there’s something else that explains both the amount/type of bacteria and the attractiveness of an individual’s skin scent to a mosquito. Secondly, Figure 2 leaves much to be desired in terms of establishing a strong trendline. Yes, if I  squint (and ignore their very leading trendline) I can see a positive correlation – but truth be told, the scatterplot looks like a giant mess, especially if you include the red squares that go with “Not HA or PA”. For a future study, I think it’d be great if they could get around this to show stronger causation with direct experimentation (i.e. extracting the odorants from Staphylococcus and/or Pseudomonas and adding them to a “clean” skin sample, etc)

With that said, I have to applaud the researchers for tackling a fascinating topic by taking a very different angle. I’ve blogged before about papers on dealing with malaria, but the subject matter is usually focused on how to directly kill or impede the parasite (Plasmodium falciparums). This is the first treatment of the “ecology” of malaria – specifically the ecology of the bacteria on your skin! While the authors don’t promise a “cure for malaria”, you can tell they are excited about what they’ve found and the potential to find ways other than killing parasites/mosquitos to help deal with malaria, and I look forward to seeing the other ways that our skin bacteria impact our lives.

(Figure 2 from paper)

Paper: Verhulst et al. “Composition of Human Skin Microbiota Affects Attractiveness to Malaria Mosquitoes.” PLoS ONE 6(12). 17 Nov 2011. doi:10.1371/journal.pone.0028991

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Making the Enemy of your Enemy

What? Another science paper post? Yup, I’m trying to get ahead of my paper-a-month deadlines by posting February’s while actually still in February!

This month’s paper comes from Science and is a topic which is extremely relevant to global health. As you probably know, malaria kills close to 1 million people a year, with most of these deaths in areas lacking in the financial resources and public infrastructure needed to tackle the disease. In addition to the socioeconomic factors, the biology of the disease itself is extremely challenging to deal with because the malaria parasite Plasmodium falciparum not only rapidly shifts its surface proteins (so the immune system can’t get a good “fix” on it) it also has a very complex multi-stage life cycle (diagram below), where it goes from being carried around by a mosquito as a sporozoite, to infecting and effectively “hiding inside” human liver cells, to becoming merozoites which then infect and hide inside human red blood cells, and then producing gametocytes which are picked up by mosquito’s which combine to once again form sporozoites. Each stage is not only difficult to target (because the parasites spend a lot of their time “hiding”), but the sheer complexity of the lifecycle means the immune system and drugs humans come up with are always a step behind.

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So, what to do? While there is active work being done to build vaccines and drugs to fight malaria, the “low-hanging fruit” is getting the upper-hand on the mosquito transmission phase. Unfortunately, controlling mosquitos has become almost as bad a nightmare as dealing with the Plasmodium parasite. The same socioeconomic factors which limit medical treatment for the disease also make it difficult to do things like exterminate mosquitos. Furthermore, pesticides not only have adverse environmental impacts (i.e., DDT) but will ultimately have limited lifetimes as the mosquito population will eventually develop resistance to them.

imageWell, enter the enterprising scientist. I can’t say for sure, but I have to believe that the scientists here must have read comic books like Spiderman or Captain America as a kid because the approach they chose feels like it came straight out of the comic book world. But, instead of building a monstrosity like the Scorpion (pictured to the right), the researchers built a super-fungus super-soldier to control malarial transmission.

Instead of giving the powers of a scorpion to smalltime thief Mac Gargan (who then named himself, appropriately, The Scorpion), the researchers engineered a fungus which naturally infects mosquitos called Metarhizium anisopliae to:

  • kill the infected mosquito more slowly (as to not push mosquitos to become resistant to the fungus)
  • coat the infected mosquito’s salivary glands with a protein fragment called SM1 to block the malaria parasites from getting there
  • produce a chemical derived from scorpions called scorpine which is extremely effective at killing malaria parasites and bacteria

Pretty cool idea, right? But does it work? Figure 3 of the chart below shows the results of their experiments:

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Mosquitos were fed on malaria-infected blood 11 days before they were dosed with our super-fungus. Typically sporozoites take about 2 weeks to build in any reasonable number in a mosquito’s salivary glands, so 14-17 days after exposure to malaria, the researchers checked the salivary glands of uninfected mosquitos (the control [C] group), mosquitos infected with non-super-fungus (the wild-type [WT] group), and mosquitos infected with the super-fungus (transgenic [TS] group). As you can see in the chart above, the TS parasite count was not only significantly smaller than both the control and wild type groups, but the control and wild type groups behaved exactly as you would expect them to (the parasite counts went up over time).

So, have we discovered a super-soldier we can count on to stop mosquito-borne illnesses? I would hold off on that for a number of reasons. First, on an experimental level, the researchers only looked at 14-17 days post-infection. To be confident, I’d like to see what this looks like with different doses of fungus and over longer periods of time and a wider range of mosquitos (as nearly 70 species of mosquito transmit malaria and I don’t even know what the numbers look like for other diseases). Secondly, its not clear to me what the most effective way to dose large populations of mosquitos are. The researchers maintain that you can spray this like a pesticide and the fungus will adhere to surfaces and stay effective for long periods of time – but that needs to be validated and plans need to be drawn up to not only pay for this (I have no idea how expense this is) but also to deploy it.

Lastly, and this is something that almost any naturalist or economist will tell you: human actions always have unintended consequences. At a first glance, it looks like the researchers covered their bases. They build what looks like a strategy which avoids mosquito resistance (and, because it uses at least two ways of controlling the parasite, is probably less vulnerable to Plasmodium resistance than drugs/vaccines). But, more research needs to be done to ascertain if there are other environmental or economic impacts of using something like this.

All in all, however, this looks like a promising start for what could be an interesting and inspired way to help control malaria.

(Image credit – Malaria lifecycle) (Image credit – the Scorpion) (Figure 3 from paper)

Paper: Fang et al., “Development of Transgenic Fungi that Kill Human Malaria Parasite in Mosquitos.” Science 331: 1074-1077 (Feb 2011) – doi:10.1126/science.1199115

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