Posted on by Dr. Francis Collins
Technological advances with potential for improving human health sometimes come from the most unexpected places. An intriguing example is an electricity-conducting biological nanowire that holds promise for powering miniaturized pacemakers and other implantable electronic devices.
The nanowires come from a bacterium called Geobacter sulfurreducens, shown in the electron micrograph above. This rod-shaped microbe (white) was discovered two decades ago in soil collected from an unlikely place: a ditch outside of Norman, Oklahoma. The bug can conduct electricity along its arm-like appendages, and, in the hydrocarbon-contaminated, oxygen-depleted soil in which it lives, such electrical inputs and outputs are essentially the equivalent of breathing.
Scientists fascinated with G. sulfurreducens thought that its electricity had to be flowing through well-studied microbial appendages called pili. But, as the atomic structure of these nanowires (multi-colors, foreground) now reveals, these nanowires aren’t pili at all! Instead, the bacteria have manufactured unique submicroscopic arm-like structures. These arms consist of long, repetitive chains of a unique protein, each surrounding a core of iron-containing molecules.
The surprising discovery, published in the journal Cell, was made by an NIH-funded team involving Edward Egelman, University of Virginia Health System, Charlottesville. Egelman’s lab has had a long interest in what’s called a type 4 pili. These strong, adhering appendages help certain infectious bacteria enter tissues and make people sick. In fact, they enable bugs like Neisseria meningitidis to cross the blood-brain barrier and cause potentially deadly bacterial meningitis. While other researchers had proposed that those same type 4 pili allowed G. sulfurreducens to conduct electricity, Egelman wasn’t so sure.
So, he took advantage of recent advances in cryo-electron microscopy, which involves flash-freezing molecules at extremely low temperatures before bombarding them with electrons to capture their images with a special camera. The cryo-EM images allowed his team to nail down the atomic structure of the nanowires, now called OmcS filaments.
Using those images and sophisticated bioinformatics, Egelman and team determined that OmcS proteins uniquely fit into the nanowires’ long repetitive chains, spacing their iron-bearing cores at regular intervals to transfer electrons and convey electricity. In fact, bacteria unable to produce OmcS proteins make filaments that conduct electricity 100 times less efficiently.
With these cryo-EM structures in hand, Egelman says his team will continue to explore their conductive properties. Such knowledge might someday be used to build biologically-inspired nanowires, measuring 1/100,000th the width of a human hair, to connect miniature electronic devices directly to living tissues. This is one more example of how nature’s ability to invent is pretty breathtaking—surely one wouldn’t have predicted the discovery of nanowires in a bacterium that lives in contaminated ditches.
 Structure of Microbial Nanowires Reveals Stacked Hemes that Transport Electrons over Micrometers. Wang F, Gu Y, O’Brien JP, Yi SM, Yalcin SE, Srikanth V, Shen C, Vu D, Ing NL, Hochbaum AI, Egelman EH, Malvankar NS. Cell. 2019 Apr 4;177(2):361-369.
Electroactive microorganisms in bioelectrochemical systems. Logan BE, Rossi R, Ragab A, Saikaly PE. Nat Rev Microbiol. 2019 May;17(5):307-319.
High Resolution Electron Microscopy (National Cancer Institute/NIH)
Egelman Lab (University of Virginia, Charlottesville)
NIH Support: National Institute of General Medical Sciences; National Institute of Allergy and Infectious Diseases; Common Fund
Posted on by Dr. Francis Collins
As many of you know, Alzheimer’s is an absolutely devastating neurodegenerative disease. It destroys the lives of loved ones with the disease, takes a terrible toll on family and friends who care for them, and costs, for patient care alone, an estimated $200 billion a year.
Alzheimer’s is the most common form of dementia, robbing those it affects of their memory, their ability to learn and think, and their personality. It worsens over time. People forget recent events, and gradually lose the ability to manage their daily lives and care for themselves. It currently affects an estimated 5.1 million Americans; this number is expected to rise to somewhere between 11 and 16 million by 2050 unless treatments can be found in the meantime.
There’s no cure for Alzheimer’s disease (AD), but biomedical researchers are testing new drugs and biochemical approaches, treatments that could stem and possibly reverse the course of the disease. They are also exploring how conditions like obesity and diabetes—which are at epidemic levels in the U.S. and worldwide—play a role. I want to tell you about a new NIH-funded experimental approach that was tried for the first time in the U.S. in November.
Neurosurgeons at Johns Hopkins Hospital, in Baltimore, MD, implanted a ‘pacemaker’ in the brain of a patient with mild AD. You are probably familiar with the concept of a pacemaker that stabilizes heart rhythms. The implanted device sends electrical pulses to the heart muscle, resetting a normal heartbeat. In some ways, this pacemaker for AD is similar. It, too, sends electrical pulses, but targets a region of the brain called the fornix—a bundle of 1.2 million axons that normally serves as a superhighway for learning, emotion, and forming memories. The fornix is one of the first regions to be destroyed by Alzheimer’s.