Wednesday, June 12, 2013

In the modern age, sterility is something that we have become accustomed to. Many years ago, the achievement of sterility was an almost inaccessible luxury as the technology was lacking. Yet despite all the advantages, we must note the drastic effect it has on microbial abundance and diversity. From the moment Leeuwenhoek first noted the presence of “wee beasties” in a droplet of water, the field of microbiology has accelerated rapidly. Today we learn more about microbes every day and the wealth of discoveries can be seen in the many recent biological and medical advancements. From polymerase chain reaction (PCR) based diagnosis to sequencing the human genome, products from bacteria notably enzymes, have been essential to the advancement of humanity. For this age of prosperity to continue it is essential that we maintain and cultivate our greatest resource. By promoting strategies to protect and strengthen the microbial diversity of the world (primarily in the kingdom of bacteria), we can assure that this vital resource will be around for generations to come.

The recent invention of antibiotics and recognition of bleach, alcohol and fire as anti-bacterial agents have revolutionized the world. In the past, prior to the implementation of sterile technique, even the most minor of surgeries could have resulted in a deadly infection. Without the discovery of antibiotics mortality rates due to common illnesses, such as pneumonia, were relatively high (30% in the case of pneumonia)5.

Haemophilus influenzae a common cause of bacterial pneumonia (© 2009 Kent Wood)

Prior to the contemporary era, people often thought that all bacteria were malignant and pathogenic. Studies performed in the last few decades have revealed that this is far from the case. Many bacteria, if not the vast majority that we interact with every day, are beneficial commensal organisms. In humans they are essential for priming our immune systems, helping us metabolize food, and even protecting us from other more nefarious bacteria11,8,12,16. As infants we are born with an immature and inexperienced immune system. It is only through breast feeding and exposure to microbes that we are able to develop a robust and diverse immune system that is able to fight off novel pathogens. A significant portion of this priming process occurs in our guts. At birth we acquire bacteria, usually from our mothers, which colonize our intestinal tracts. Studies have shown that a baby’s immune system is stronger (more developed) when the child underwent a vaginal birth in comparison to a caesarian section15. Studies in mice and rats have also confirmed the necessity of bacteria in the extraction of nutrients and energy from food12,17.

Building off these studies, researchers have furthered their understanding of gut microbiomes. With the recent surge in next-generation sequencing technologies, it is getting easier and easier to analyze the microbial communities in environments with high levels of genetic diversity (i.e. intestines)6. Organisms ranging from cows to zebrafish have had their gut microbiota sequenced3,13. The results reveal that there are many conserved species across phyla and that these microbes are likely to be essential in breaking down certain types of nourishment4. In the images below we can see the similarities between the microbiomes in the guts of cows and zebrafish. In addition, I included an animated image to remind us that the bacterial interactions within the gut, are dynamic and constantly changing.

Microbiome of the cow gut4

Microbiome of the zebrafish gut15

Fluorescent bacteria within the gut of a zebrafish

Another interesting use of bacteria is in the conservation of eukaryotes. Many plants and animals have specific bacteria that are associated with them. These symbiotic relationships tend to be mutualistic in nature. One great example is the cutaneous bacterial community found on the redback salamander, Plethodon cinereus. Scientists noticed that these salamanders were innately more resistant to chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis. Further investigation suggested that this resistance was due to anti-fungal proteins produced by the salamanders’ resident cutaneous bacteria1. Researchers in Kings Canyon National Park are inoculating lakes with these bacteria in hopes that they may confer chytridiomycosis resistance to the endangered yellow-legged frogs living there14. An important point to take home here is that the extinction of eukaryotic organisms can also result in the loss of the bacteria associated with said organism. Although the redback salamander is relatively common, the extinction of it and/or its associated microbiota could be a death sentence for amphibians worldwide.

Having elucidated the importance and significance of microbial diversity, we will now venture into terra incognita (uncharted territories).

Firstly, how would it be possible to make sure that we maintain certain species of bacteria? One option would be to store all species in large cryogenic libraries.

On the other hand, is it necessary to preserve every species or is the preservation of individual genes or sets of genes a better option?

It is widely understood that one of the primary methods of prokaryotic genetic inheritance is through horizontal gene transfer; the transfer of genes between different species in a non-temporal and non-generational fashion. Perhaps instead of preserving individual species, we could preserve the individual genes that make certain bacteria different from other bacteria. This would be a far simpler endeavor than preserving every unique species as molecular cloning techniques are already well established.

Another important topic is where to focus the efforts. It is not entirely clear how many different bacteria there are on earth but it would probably be fair to say that identifying and defining each species would take more than a single human lifetime. It might be best to focus on locations that are endangered or at risk of being drastically altered in a way that might affect the bacteria present there. Possible locations include bio-diversity hotspots and other locations near the equator. In addition, lands that are likely to be changed due to recent surges in human activity (e.g logging in the amazon rainforests) are other possible locations of focus.

On this point, it is interesting to consider some of the past microbial-derived discoveries in terms of their value to the human race. Heat-stable polymerases, such as Taq, that were discovered in hot-springs (see picture below) or hydrothermal vents were key in developing a research method that is fundamental to many aspects of molecular biology, the polymerase chain reaction (PCR). Without these bacterial polymerases it is probable that the human genome project would still not be complete today. Maybe focusing on extreme environments is the ideal, as the future of the earth is unclear and we never know when we will need enzymes that function in super high temperature (global warming?) or super cold temperatures (interstellar travel?).

Hot springs potentially similar to the location where Taq was discovered (microbewiki.kenyon.edu)

Regardless, it seems foolish to not consider the importance of preserving microbial species. A good first step would be to lay out all the benefits and risks to see how urgent and necessary this kind of endeavor would be. Investigating natural rates and cycles of bacterial extinction would be a good place to start. Another starting point would be deciding which approach to take (bacterial species vs. bacterial genes). It is important to take into account the cost and efficiency of a given preservation method.

In conclusion, throughout history bacteria have provided us with a substantial array of benefits. More often than not it took hundreds, even thousands, of years before people were able to tap into the resources provided by bacteria (e.g. Taq, restriction enzymes, etc…) If we want to maximize the potential of similar new discoveries, it is crucial that we begin thinking about and investigating bacterial conservation NOW.

1)      Becker, Matthew H., and Reid N. Harris. “Cutaneous Bacteria of the Redback Salamander Prevent Morbidity Associated with a Lethal Disease.” PLoS ONE 5, no. 6 (June 4, 2010): e10957. doi:10.1371/journal.pone.0010957.
2)      Brandt, L. J. (2012). Fecal transplantation for the treatment of Clostridium difficile infection. Gastroenterol Hepatol (N Y), 8(3), 191-194.
3)      Broderick, N. A., & Lemaitre, B. (2012). Gut-associated microbes of Drosophila melanogaster. Gut Microbes, 3(4), 307-321. doi: 10.4161/gmic.19896
4)      De Menezes, Alexandre B., Eva Lewis, Michael O’Donovan, Brendan F. O’Neill, Nicholas Clipson, and Evelyn M. Doyle. “Microbiome Analysis of Dairy Cows Fed Pasture or Total Mixed Ration Diets.” FEMS Microbiology Ecology 78, no. 2 (2011): 256–265. doi:10.1111/j.1574-6941.2011.01151.x.
5)      “Dead Guts Spill History of Extinct Microbes: Fecal Samples from Archeological Sites Reveal Evolution of Human Gut Microbes.” Accessed June 3, 2013. http://www.sciencedaily.com/releases/2012/12/121212205609.htm.
6)      Dowling HF. Frustration and foundation: Management of pneumonia before antibiotics. JAMA 1972;220:1341-1345. (Historical review)
7)      Gevers, D., Knight, R., Petrosino, J. F., Huang, K., McGuire, A. L., Birren, B. W., Huttenhower, C. (2012). The Human Microbiome Project: a community resource for the healthy human microbiome. PLoS Biol, 10(8), e1001377. doi: 10.1371/journal.pbio.1001377
8)      Gomez, F., Monsalve, G. C., Tse, V., Saiki, R., Weng, E., Lee, L., Clarke, C. F. (2012). Delayed accumulation of intestinal coliform bacteria enhances life span and stress resistance in Caenorhabditis elegans fed respiratory deficient E. coli. BMC Microbiol, 12, 300. doi: 10.1186/1471-2180-12-300
9)      Gourbeyre, P., Denery, S., & Bodinier, M. (2011). Probiotics, prebiotics, and synbiotics: impact on the gut immune system and allergic reactions. J Leukoc Biol, 89(5), 685-695. doi: 10.1189/jlb.1109753
10)  Hot_springs.png (PNG Image, 728 × 497 Pixels). Accessed June 2, 2013. http://microbewiki.kenyon.edu/images/0/02/Hot_springs.png.
11)  Lin, Anna L., Bernward A. Mann, Gelsy Torres-Oviedo, Bryan Lincoln, Josef Kas, and Harry L. Swinney. “Localization and Extinction of Bacterial Populations Under Inhomogeneous Growth Conditions.” Biophysical Journal 87, no. 1 (July 2004): 75–80. doi:10.1529/biophysj.103.034041.
12)  Meningitis-bacteria.jpg (JPEG Image, 750 × 501 Pixels). Accessed June 11, 2013. http://cdn.c.photoshelter.com/img-get/I00007kDHJu3OH9M/s/750/750/Meningitis-bacteria.jpg.
13)  Reddy, B S, and B S Wostmann. “Intestinal Disaccharidase Activities in the Growing Germfree and Conventional Rats.” Archives of Biochemistry and Biophysics 113, no. 3 (March 1966): 609–616.
14)  Rex, Erica. “Toiling to Save a Threatened Frog.” The New York Times, October 4, 2010, sec. Science. http://www.nytimes.com/2010/10/05/science/05frog.html.
15)  Roeselers, Guus, Erika K Mittge, W Zac Stephens, David M Parichy, Colleen M Cavanaugh, Karen Guillemin, and John F Rawls. “Evidence for a Core Gut Microbiota in the Zebrafish.” The ISME Journal 5, no. 10 (October 2011): 1595–1608. doi:10.1038/ismej.2011.38.
16)  Thavagnanam S, Fleming J, Bromley A, Shields MD, Cardwell, CR (2007). "A meta-analysis of the association between Caesarean section and childhood asthma". Clin. And Exper. Allergy 38(4): 629–633. doi:10.1111/1365-2222-7-2780
17)  “The Influence of Diet on the Gut Microbiome | Second Genome.” Accessed June 2, 2013. http://www.secondgenome.com/2011/06/the-influence-of-diet-on-the-gut-microbiome/.
18)  Tito, Raul Y., Dan Knights, Jessica Metcalf, Alexandra J. Obregon-Tito, Lauren Cleeland, Fares Najar, Bruce Roe, et al. “Insights from Characterizing Extinct Human Gut Microbiomes.” Edited by Michael Hofreiter. PLoS ONE 7, no. 12 (December 12, 2012): e51146. doi:10.1371/journal.pone.0051146.

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