Superbugs resistant to multiple antibiotics are quickly adapting to renew the threat from lethal diseases we once thought defeated. If they continue to learn and change at this rate, will we be left facing new plagues of tuberculosis, septic wounds and infectious diseases with nothing left to fight them?
Not if researchers like AJ Singhal can prevent it. A research associate at iXpressGenes on the Huntsville campus of the HudsonAlpha Institute for Biotechnology, Singhal is the principal investigator in a search for potential new antibiotics produced by strands of DNA from bacteria that survive and thrive in the earth’s most extreme environments.
“Bacteria are continually struggling and fighting with other bacteria. They produce novel compounds to help them compete with other organisms, and those that succeed may be creating something that could work against the germs that cause human diseases,” Singhal said.
“The problem, until now, has been numbers. In the human body alone, there are typically more microbe cells than human cells. The quantity of novel bacteria in even a small sample of ordinary garden soil is also vast and impossibly large to study one by one. We don’t even know what 90 percent of them are, or what substances they might produce. Some we couldn’t culture, and those we can would take far too long to culture and investigate their properties individually. The only way to study such a high volume of bacteria is with a metagenomics approach.“Metagenomics is becoming a very active field. With the biotechnologies of rapid gene sequencing and bioinformatics, we can look at all the DNA in a sample at one time and sort out clusters that have similarities to strands of genes with known pathways of activity in our databases. When we identify a promising sequence, we engineer it into bacteria, and then study how it works and the substances it produces. Those showing the greatest potential will be tested against target pathogens.”
When the first phase of this study is complete, the most promising samples will be sent to the Chemical and Biological Defense Division of the Department of Defense for testing against anthrax and other biological weapons, as well as drug-resistant pathogens that are of concern in health care. The next phase will be turning successful samples into drugs and confirming that they can be used safely and effectively in human patients.
What sets Singhal’s work apart is the unusual nature of the samples he is studying. iXpressGenes is known for its work in proteins, enzymes and genetic engineering research, and has a unique background in microgravity experiments in space and extremozymes from its library of samples from some of the most difficult environments on earth.“Our founders went around the world collecting samples of bacteria that have adapted to thrive in places most life wouldn’t be able to survive. We have bacteria from arctic permafrost, and from acidic, alkali and high salt environments. We also have genomes from the hot volcanic deep sea vents of the Atlantic Ridge,” Singhal said. “Something different about their DNA allows them to live where other life can’t exist. This is the first time anyone has looked at these samples to evaluate their therapeutic potential. It’s going to be exciting to see whether the differences in their genome will translate into novel antibiotics.”Singhal is working with HudsonAlpha Genomic Services Lab Director Shawn Levy, PhD, in sequencing DNA from the samples. He is also consulting with Mark Liles, PhD, from Auburn University.
“The sequencing capabilities at HudsonAlpha are incredible,” Singhal said. “We’re working with the Illumina platform, which has the powerful, high speed capabilities for full genome sequencing. Dr. Liles at Auburn has also been extremely helpful in sharing his experience in using the antibiotic potential in bacteria to kill other bacteria. He is already using bacteria as a drug in fish populations to save them from an infectious pathogen.”
What researchers learn from sequencing metagenomes of bacteria has the potential to go well beyond the possibility of new antibiotics to fight anthrax and resistant diseases.“The sequencing data could be used to develop drugs to fight cancer, antivirals, anti-inflammatories and other therapeutic medications,” Singhal said. “We have high hopes that treatments for many human diseases are here in the genomes of the world around us, waiting to be discovered