Decoding Messages in the Body’s Microscopic Metropolises 

by Aliyah Kovner

Newswise — A study aimed at identifying and examining the small messenger proteins used by microbes living on and inside humans has revealed an astounding diversity of more than 4,000 families of molecules – many of which have never been described previously.

The research, led by Stanford University and now published in Cell, lays the groundwork for future investigations into how the trillions of bacteria, archaea, and fungi that compose human microbiomes compete for resources, attack and co-exist with one another, and interact with our own cells. “Because it is much more difficult to search for sequences encoding small proteins than it is to trawl for large proteins, our comprehension of the small proteins expressed by microbial communities has always been lacking,” said Nikos Kyrpides, a Berkeley Lab senior scientist who contributed to the work. Yet, very small proteins made of 50 or fewer amino acids, which can move though cell walls and membranes, perform many essential tasks that mediate an organism's interactions with the environment. These functions, combined with the fact that they are easier to synthesize and manipulate than large molecules, make small microbial proteins a potential source of new medicines.

Learn more about this study here.

X-ray Experiments Contribute to Studies of a Drug Now Approved to Combat Tuberculosis

By Glenn Roberts

The U.S. Food and Drug Administration has approved a new antibiotic that, in combination with two existing antibiotics, can tackle one of the most formidable and deadly treatment-resistant forms of the bacterium that causes tuberculosisThe new antibiotic, called pretomanid (PA-824), can work with the other drugs like a deadly cocktail – triggering the bacteria (Mycobacterium tuberculosis) to release nitric oxide. This can burst the bacteria’s cell walls and poison the microorganisms. 

Studies exploring the structure and function of the new drug benefited from X-ray experiments at Berkeley Lab’s Advanced Light Source (ALS). ALS experiments detailed the molecular structure of Ddn, a tuberculosis bacterium enzyme, in the presence and absence of a coenzyme (F420). Coenzymes, or cofactors, can help enzymes carry out chemical reactions. SLAC National Accelerator Laboratory’s Stanford Synchrotron Radiation Lightsource (SSRL) also carried out related experiments. ALS and SSRL are DOE Office of Science user facilities.

Drug-resistant strains of tuberculosis bacteria infected an estimated 558,000 people in 2017. Existing treatments are often unsuccessful and can include as many as eight antibiotics taken for 18 months or longer. The World Health Organization has reported a 55% success rate in treating multi-drug resistant tuberculosis using existing treatments.

In a Phase III clinical trial, the three-drug regimen that includes the new FDA-approved antibiotic cleared the infection within six months from 95 of 109 patients who were unresponsive to previous treatments.

Work at the ALS has also benefited research into cancer-fighting drugs, and the fight against the Ebola and Zika viruses, among other examples.

Read the FDA announcement:

FDA approves new drug for treatment-resistant forms of tuberculosis that affects the lungs

A Chemical Reaction Close-Up: New Technology Gives a Glimpse of Solar Fuel Generation in Action

By Aliyah Kovner

Electrochemical devices that use sunlight to generate fuel represent a promising means of harvesting sustainable energy; but currently, none are efficient enough for real-world applications. One of the main reasons for the slow development is the difficulty in observing and measuring what is happening at the liquid-catalyst interface – the location in the cell where the fuel-producing chemical reactions are taking place – without interfering with the processes. 

Hoping to break this barrier, scientists at the Joint Center for Artificial Photosynthesis, a Department of Energy Innovation Hub based partly at Berkeley Lab, have invented a cell that is specially designed to allow for unobtrusive observation of an isolated, operating catalyst. A description of the cell is published in Physical Chemistry Chemical Physics

“Our design can mimic how a catalyst behaves in a full device, thanks to a fast-flow design that constantly replenishes the liquid at the interface,” said lead author Walter Drisdell, a Berkeley Lab chemist.  “And the cell shape allows X-ray beams to graze over the surface, showing us the chemistry at the interface specifically.”

The cell is expected to help scientists engineer and test new catalyst materials, which can be used in next-generation solar fuel devices that split water to produce hydrogen gas and convert carbon dioxide emissions into fuels like ethanol.

“We intend to make the cell available to users at the DOE’s Stanford Synchrotron Radiation Lightsource (SSRL) facility so the entire science community can benefit from it,” said Drisdell. SSRL is a DOE Office of Science user facility.

Media contact: Laurel Kellner, [email protected], 510-590-8034