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Tag: immunity

New Year’s Special: Flies in Space (and other news from 2014)

Fruit fly researchers published thousands of papers in 2014, and several of them were picked up by the media. I even reviewed a couple of these popular stories on this blog. In April, the Seghal lab published a paper showing that sleep loss in young flies led to abnormal brain development and behavioral deficits in adulthood. In September, researchers in the Walker lab showed that increasing the levels of a molecule called AMPK in the guts of fruit flies could extend their lifespan, providing hope that we may one day be able to develop a pill to slow aging.

The most heartwarming story of 2014 came out in June, after a sixth-grader’s science fair project was published in the peer-reviewed journal PLoS One. Father and son worked together to discover that the artificial sweetener Truvia is toxic to fruit flies. Erythritol, the main ingredient of Truvia, is safe to consume for humans but quickly kills these winged pests. The researchers who worked on the project are now pursuing the possibility of using erythritol as a safe insecticide for fruit flies and other insects.

But perhaps the biggest news from 2014 involves flies… in space! Although many animals have been to space over the past several decades, fruit flies have recently proven to be ideal for studying the effects of zero gravity on earthly bodies. It’s widely known that microgravity (zero gravity) leads to rapid loss of bone density and muscle weakness, which is why astronauts spend a lot of time exercising while they’re in space. But did you know that microgravity also negatively affects the cardiovascular and immune systems? NASA recently announced a plan to send humans to Mars by 2030, but first, they need a better understanding of the long-term effects of microgravity on the body.

Fruit fly with fungusThis fruit fly is covered with a fungal infection after its immune system was compromised by 2 weeks in space. Image credit: Deborah Kimbrell/UC Davis

Space flies made the news in January 2014 after the results of a successful experiment were published in PLoS One by the Kimbrell lab. Researchers sent flies into space for 12 days to determine how zero gravity affects their immune system. It may seem like a short trip, but that’s about half the lifespan of your average fly (roughly the equivalent of sending a human into space for 40 years!). The researchers reported that flies subjected to microgravity had reduced ability to fight off a fungal infection compared to their earthbound brethren. Also interestingly, flies exposed to hypergravity (even stronger than Earth’s gravity) showed an increased ability to fight off the infection. The difference in immunity was caused by changes in the Toll pathway, an immune response which is also present in humans and other mammals. These promising results provided a leap forward in understanding how astronauts’ immune system may also be affected by microgravity.

Three more fruit fly experiments were launched into space in 2014. In April, a collaborative group led by Dr. Peter Lee sent flies into space for 30 days to study the effects of microgravity on the cardiovascular system (the experiment was named The HEART FLIES study). The second experiment was launched in September by a team at NASA’s Ames Research Center led by Dr. Sharmila Bhattacharya. The researchers hope to better understand how flies adapt to microgravity by studying changes in behavior.

The final experiment, launched in December 2014, was the maiden voyage of NASA’s newly-developed Fruit Fly Lab-01 project. NASA’s Fruit Fly Lab is a collaborative effort with a sophisticated set-up that researchers hope will improve our understanding of how spaceflight affects immune function. After 30 days in space, researchers will analyze the immune systems from three generations of flies exposed to various levels of gravity.

The results of these three missions should be published this year. Researchers at NASA are hoping that the findings will help them predict the physical challenges that astronauts will face during future space exploration, including the first human mission to Mars. NASA is also planning yearly sequels to their Fruit Fly Lab’s debut mission, so stay tuned!

References:

  • Baudier K.M., Nirali Patel, Katherine L. Diangelus, Sean O’Donnell & Daniel R. Marenda (2014). Erythritol, a Non-Nutritive Sugar Alcohol Sweetener and the Main Component of Truvia®, Is a Palatable Ingested Insecticide, PLoS ONE, 9 (6) e98949. DOI: http://dx.doi.org/10.1371/journal.pone.0098949
  • Taylor K., Michael D. George, Rachel Morgan, Tangi Smallwood, Ann S. Hammonds, Patrick M. Fuller, Perot Saelao, Jeff Alley, Charles A. Fuller & Deborah A. Kimbrell (2014). Toll Mediated Infection Response Is Altered by Gravity and Spaceflight in Drosophila, PLoS ONE, 9 (1) e86485. DOI: http://dx.doi.org/10.1371/journal.pone.0086485
  • NASA.gov

Breaking Research: A method by which invading bacteria avoid detection could also be our key to defeating them

Have you ever wondered how our body recognizes when it’s being invaded by harmful bacteria? Nearly all forms of life—from single-celled organisms all the way to humans—have an “innate” immune system, which has evolved to recognize cellular components shared by broad groups of pathogens. One such example is peptidoglycan, a molecule found on the cell walls of virtually all bacteria. Peptidoglycan forms a sort of “load-bearing mesh” required for the bacteria to maintain their shape and is therefore an essential part of their structure. As a result, our immune systems have evolved to recognize peptidoglycan as a danger signal and will trigger an immune response when it is detected.

But just as our innate immune system has evolved to recognize invaders bearing peptidoglycan, bacteria have also evolved to escape detection. In a recent paper published in eLife by the Filipe lab, researchers used fruit flies to study how some bacteria can remain undetected by its host. Understanding how bacteria avoid detection will help us develop new ways to defeat them by preventing them from evading our immune system. This could reduce the need for antibiotics, which is particularly important now that antibiotic-resistant bacteria are becoming painfully common (in 2014, the World Health Organization declared antibiotic resistance a major threat to public health).

Gram-negative and -positive bacteriaThe difference between Gram-negative and Gram-positive bacteria. Image source

So how do bacteria with peptidoglycan conceal themselves from our immune system? Previous work has categorized bacteria into two groups based on the way they cover up their peptidoglycan mesh: Gram-negative bacteria, which have a full membrane surrounding the peptidoglycan molecules, and Gram-positive bacteria, which have the mesh directly outside the cell wall. Instead of a full membrane, Gram-positive bacteria have layers of molecules that stick out of the cell wall and block access to the peptidoglycan. Because of this, it has long been thought that the immune system can only detect peptidoglycan when fragments have been snipped off of the bacterial walls (when bacteria need to grow and divide, they must break down their mesh and then rebuild it).

But now, researchers have uncovered a new twist to this story. Recent findings have suggested that under certain conditions, the immune system can actually recognize peptidoglycan while it’s still a part of the bacterial cell wall. So the authors of this paper asked: Have bacteria evolved other methods to prevent this from happening?

To answer this question, they infected fruit flies with Staphylococcus aureus (S. aureus), a Gram-positive strain of bacteria related to MRSA. They observed how well the fruit fly hosts were able to defend against the invaders, and then mutated parts of the bacteria to determine how each manipulation affected the hosts’ ability to survive. The authors learned that S. aureus releases a molecule called Atl, which they found was responsible for trimming off pieces of peptidoglycan that stick up above the bacteria’s protective layer. When the bacteria couldn’t release Atl, the flies were much more likely to survive the infection because their immune system could more easily recognize the intruders and fight them off.

How can this help us humans?  The mammalian innate immune system is similar to that of flies, and also recognizes peptidoglycan as a trigger for activating an immune response. Thus, if bacteria that infect humans use the same evasive maneuvers, it could be possible to develop a drug that targets and disables Atl and other peptidoglycan-snipping molecules. This would allow our immune systems to better recognize and fight back against bacterial infections and reduce the need for antibiotics.

The authors have already done some of the work toward this goal. To find out if strains of bacteria known to endanger humans use the same avoidance mechanism, they also infected flies with MRSA, a dangerous antibiotic-resistant strain of bacteria often found in hospitals, and Streptococcus pneumoniae, which is a frequent cause of pneumonia in developed countries and a major cause of infant mortality in developing countries. That found that both of these bacteria use Atl to shave their surface and avoid recognition by the immune system. Future research may therefore lead to treatments that prevent these bacteria from going into hiding, allowing our immune system to hunt them down and do its job with ease.

Reference:

  • Atilano M.L., Filipa Vaz, Maria João Catalão, Patricia Reed, Inês Ramos Grilo, Rita Gonçalves Sobral, Petros Ligoxygakis, Mariana Gomes Pinho & Sérgio Raposo Filipe (2014). Bacterial autolysins trim cell surface peptidoglycan to prevent detection by the Drosophila innate immune system, eLife, 3 DOI: http://dx.doi.org/10.7554/elife.02277

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