(Un)Natural Born Killers

Its name is coli. Escherichia coli. This James Bond of the microscopic world is not just any E. coli bacterium—it has been carefully engineered to assassinate bodily pathogens with alarming specificity. Killer E. coli are not the only genetically modified bacteria. Scientists have begun using synthetic biology techniques to amass a veritable army of altered microbes that have the ability to target unwanted prey. From human pathogens to cancer cells to malaria parasites, these genetically modified bacteria signal a revolution in fields as diverse as medicine and climate change. Of course, the idea of engineering any type of organism is very controversial. Debates about genetically modified organisms (GMOs) have been raging for several years. Public acceptance of these creatures is just one hurdle. Engineered bacteria must also be proven safe before they can benefit humans. Despite these challenges, synthetically made and specifically targeted bacteria show significant promise in ameliorating the environment, reducing clinical reliance on antibiotics, contributing to global public health control, and transforming cancer treatment.

Engineered bacteria have a potentially important role in the treatment of both human and environmental disease. We know that carbon dioxide contributes to global climate change by warming the atmosphere. One group found that Caulobacter vibrioides bacteria could be engineered to remove carbon dioxide from the air by fixing it in crystals of calcium carbonate [5]. Expanding the scale of this experiment could allow these specialized bacteria to have a significant effect on climate change. Other researchers have examined the potential of engineered bacteria to engage in environmental remediation by sequestering pollutants such as heavy metals [9]. Our future on this planet depends on our ability to be sustainable, and both minimizing climate change and engaging in environmental remediation are incredible opportunities that we must embrace.

In terms of human disease, scientists in Singapore recently created synthetic E. coli bacteria with the ability to target, hunt down, and kill pathogenic pneumonia-causing Pseudomonas aeruginosa bacteria [3, 8]. The group’s specialized E. coli can sense molecules produced by the P. aeroginosa colonies, migrate towards those signals, and annihilate the defensive biofilm, a sticky coating that can protect pathogenic colonies. After removing this barrier, the E. coli secretes an antimicrobial peptide to kill the pathogens [8]. This killer bacterium’s advantage over traditional antibiotic drugs is significant. Even short-term use of antibiotics can result in major changes in the human microbiota; one study found that antibiotic treatment for an infection of the bacterium H. pylori resulted in prolonged disturbance and even antibiotic resistance in host microbiota [4]. Jakobsson et al. called for restrictive use of antibiotics in order to avoid both antibiotic resistance and future treatment failure [4]. Engineered killer E. coli eliminates the problem of antibiotic overuse and could reduce the emergence of antibiotic resistance, especially in hospitals where antibiotic-resistant bacteria is a major problem.

E. coli is not the only bacterium with a license to kill. Recently, researchers have used Pantoea agglomerans and Wolbachia bacteria to combat malaria parasites in mosquitoes. P. agglomerans, a type of mosquito symbiotic bacterium, was synthesized to secrete proteins that kill the malaria parasite. These engineered P. agglomerans bacteria were able to prevent parasite development by approximately 98% in the mosquito midgut [10]. Insect-infecting Wolbachia bacteria can be inherited from parent to offspring and, within the mosquito vector Anopheles stephensi, can reduce the amount of the parasite that causes human malaria [7]. Given the incredible global burden of malaria, novel strategies such as the use of modified bacteria are both promising and powerful.

Engineered bacteria also show considerable promise as a therapy for cancer. In 2006, Anderson et al. opened up possibilities to manipulate the ability to sense one’s environment by programming engineered bacteria to sense the microenvironment of a tumor and then invade those cancer cells [1]. Just seven years later, scientists have produced several types of bacteria to kill many different types of cancer cells. Because cancer is a heterogenous disease, with many different manifestations and a variety of distinct treatment strategies, we will need an arsenal of engineered bacteria to defeat the vast variety of cancer types. One group of researchers synthesized bacteria to express antibodies that can detect cancer cells. The bacteria can then kill the cancer cells by bombarding them with toxic compounds [2]. Specifically, this group created a strain of Salmonella typhimurium bacteria to express antibodies that target CD20, which is a cell-surface protein expressed on lymphomas. The engineered Salmonella, upon recognition of the lymphoma cell, delivered an enzyme to the cancer cells that converts a certain drug, ganciclovir, into an active, toxic form when inside the cancer cell [6]. Usage of engineered bacteria to fight cancer is a revolutionary treatment option that eliminates adverse side effects of chemotherapy such as hair loss, nausea, and diarrhea. Given the incredibly painful journey that cancer patients face, the promise of a new therapy that can significantly reduce their suffering is empowering and long overdue.

The future is bright for engineered bacteria. Research has shown that these bacteria can be targeted to kill pathogens, fight malarial parasites, destroy cancer cells, and clean up the environment. However, despite the benefits for disease treatment, public health, and the planet as a whole, there are still challenges that must be overcome. Engineered bacteria are genetically modified organisms and as such they are not fully accepted by either regulatory agencies or the public. Safety must always come first, but the incredible possibilities that engineered bacteria carry should not be ignored or suppressed out of fear alone. More research is needed, of course, but it is exciting to imagine a future in which so many of our problems could be solved by microscopic secret agents.

References

  1. Anderson, JC, Clarke, EJ, Arkin, AP, and Voigt, CA. “Environmentally controlled invasion of cancer cells by engineered bacteria.” Journal of Molecular Biology 355, no. 4 (2006): 619-627.
  2. Ben-Jacob, E. “Engineering Trojan-horse bacteria to fight cancer.” Blood 122, no. 5 (2013): 619-620.
  3. Hwang, In Young, Tan, Mui Hua, Koh, Elvin, Ho, Chun Loong, Poh, Chueh Loo, and Chang, Matthew Wook. “Reprogramming Microbes to Be Pathogen-Seeking Killers.” ACS Synthetic Biology (2013). doi: 10.1021/sb400077j.
  4. Jakobsson, HE, Jernberg, C, Andersson, AF, Sjolund-Karlsson, M, Jansson, JK, and Engstrand, L. “Short-Term Antibiotic Treatment Has Differing Long-Term Impacts on the Human Throat and Gut Microbiome.” PLoS ONE 5, no. 3 (2010). doi:10.1371/journal.pone.0009836.
  5. Krieger, Kim. “Genetically Engineered Bacteria Could Help Fight Climate Change.” ScienceNow (2012).
  6. Massa, PE, Paniccia, A, Monegal, A, de Marco, A, and Rescigno, M. “Salmonella engineered to express CD20-targeting antibodies and a drug-converting enzyme can eradicate human lymphomas.” Blood 122, no. 5 (2013): 705-714.
  7. Milius, Susan. “Malaria mosquito dosed with disease-fighting bacteria.” ScienceNews (2013).
  8. Peplow, Mark. “Engineered bacterium hunts down pathogens.” Nature (2013). doi:10.1038/nature.2013.13727.
  9. Singh, JS, Abhilash, PC, Singh, HB, Singh, RP, and Singh, DP. “Genetically engineered bacteria: an emerging tool for environmental remediation and future research perspectives.” Gene 480 (2011): 1-9.
  10. Wang, S, Ghosh, AK, Bongio, N, Stebbings, KA, Lampe, DJ, and Jacobs-Lorena, M. “Fighting malaria with engineered symbiotic bacteria from vector mosquitoes.” Proceedings of the National Academy of Sciences of the United States of America 109, no. 31 (2012): 12734-12739.

Viggy Parr is a junior at Georgetown University majoring in Biology of Global Health. She is very interested in malnutrition and plans to pursue a career in public health upon her graduation from Georgetown. Follow The Triple Helix Online on Twitter and join us on Facebook.

 

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  • Becky Stapp

    Loved the article on “Unnatural Born Killers”. Using biological warfare on disease and environmental hazards is both brilliant and necessary. Thank you Miss Parr for telling us about it!