NIAID Now | March 29, 2019
At first glance, the inside of the human intestine is a far cry from hot springs in the deep sea. But somewhere in the ancient past, bacteria from the deep sea made their way into mammalian guts, carrying evidence of their origins in their genes—highly-conserved fragments of genetic material that have made the bacteria tough and adaptable enough to colonize new environments.
Thanks to new advances in genetic sequencing technology, scientists have been able to peer into the origins of bacteria and viruses from all over the world—as two scientists recently discussed in a lecture at the National Institutes of Health, “Exploring Deep Sea Ecosystems and Human Disease.” As part of NIH’s Demystifying Medicine lecture series, Dr. Stefan Sievert, an Associate Scientist in the Biology Department of the Woods Hole Oceanographic Institution, and Dr. John Dekker, Chief of the Bacterial Pathogenesis and Antimicrobial Resistance Unit in NIAID’s Laboratory of Clinical Immunology and Microbiology, discussed how pathogens have evolved from microbes living in some of the world’s most inhospitable environments, and how the latest science is helping us track and fight them.
Bacteria from the abyss
Dr. Sievert has spent years studying the microbiomes of some of the ocean’s most hostile regions, including hot springs in the Pacific Ocean, where giant tube worms, crabs, and pallid octopuses eke out a living in the mixing zone of the frigid ocean and the hot vent fluids. As it bubbles up from deep within the ocean crust, the vent fluid carries chemicals acquired from interacting with rocks at high temperatures and pressure, like hydrogen sulfide and hydrogen. In combination with oxygen or nitrate derived from seawater, these chemicals sustain microorganisms that have evolved to use chemosynthesis—the generation of biomass from carbon dioxide by using chemical energy rather than light—in an environment with no light and little to no oxygen. Chemosynthetic bacteria have been found on the backs of the heat-tolerant polychaete worm Alvinella pompejana, and inside Riftia tube worms in a specialized organ called the trophosome, where they provide food to the animal in an intimate symbiotic association. These types of bacteria also live independently of other organisms, forming the base of the food web of deep-sea vent ecosystems.
To study these bacteria, Dr. Sievert and his colleagues must send submersibles and rovers down to the abyss to physically take samples. To determine the vent ecosystems’ productivity, they bring back the samples to their research vessel with specially-built equipment to incubate the samples under the same conditions they would experience at depth, including the intense pressure. Recently, they have also developed instrumentation to make these measurements directly at the seafloor.
Hunting genes with a “candy bar”
These revelations have come about in large part due to evolving sampling techniques for bacterial genomes—and in the years to come, rapid genetic sequencing will likely get even faster and easier. In his portion of the lecture, NIAID’s Dr. John Dekker discussed how next-generation sequencing approaches have led to some surprising breakthroughs in rapid discovery of new and unexpected pathogens and may lead to further discoveries in the future.
In one of these approaches, based on nanopore technology, an enzyme feeds a single unzipped strand of DNA or RNA through a nanopore—a narrow caliber protein channel. Detectors pick up on the electrical disturbances caused by this process, and are able to decipher the base pair sequences from these fluctuations. The machine itself is about the size of a candy bar, and can run off the power from a standard laptop USB port. Their size and efficiency makes them both portable and versatile: During the 2015 Ebola outbreak, a team of researchers put together a “mobile lab” that could fit in commercial airline luggage—and could rapidly sequence the genome of the Ebola virus. Nanopore sequencing can also be used to identify antimicrobial resistance genes in bacteria faster than traditional methods that require cultivating bacteria in the presence of antibiotics. These findings could lead to advances in combatting antimicrobial resistance. Dr. Dekker also discussed a published case of a boy whose illness could not be identified by traditional methods after months of testing, but whose infection was successfully cured after next-generation sequencing was used to identify the bacteria that had infected him, allowing treatment with antibiotics. Bacteria may prove to be our most tenacious pathogenic foes, especially as antibiotic resistance spreads. However, with techniques and dedicated researchers like these, we may still be able to outpace them.