Warren symposium follows legacy of geneticist giant

If we want to understand how the brain creates memories, and how genetic disorders distort the brain’s machinery, then the fragile X gene is an ideal place to start. That’s why the Stephen T. Warren Memorial Symposium, taking place November 28-29 at Emory, will be a significant event for those interested in neuroscience and genetics. Stephen T. Warren, 1953-2021 Warren, the founding chair of Emory’s Department of Human Genetics, led an international team that discovered Read more

Mutations in V-ATPase proton pump implicated in epilepsy syndrome

Why and how disrupting V-ATPase function leads to epilepsy, researchers are just starting to figure Read more

Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more
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biofilms

Rescuing existing antibiotics with adjuvants

One of the speakers at Thursday’s Antibiotic Resistance Center symposium, Gerald Wright from McMaster University, made the case for fighting antibiotic resistance by combining known antibiotics with non-antibiotic drugs that are used to treat other conditions, which he called adjuvants.

As an example, he cited this paper, in which his lab showed that loperamide, known commercially as the anti-diarrheal Immodium, can make bacteria sensitive to tetracycline-type antibiotics.

Wright said that other commercial drugs and compounds in pharmaceutical companies’ libraries could have similar synergistic effects when combined with existing antibiotics. Most drug-like compounds aimed at human physiology follow “Lipinski’s rule of five“, but the same rules don’t apply to bacteria, he said. What might be a more rewarding place to look for more anti-bacterial compounds? Natural products from fungi and plants, Wright proposed.

“I made a little fist-pump when he said that,” says Emory ethnobotanist Cassandra Quave, whose laboratory specializing in looking for anti-bacterial activities in medicinal plants.

Medical thnobotanist Cassandra Quave collecting plant specimens in Italy.

Medical ethnobotanist Cassandra Quave collecting plant specimens in Italy

Indeed, many of the points he made on strategies to overcome antibiotic resistance could apply to Quave’s approach. She and her colleagues have been investigating compounds that can disrupt biofilms, thus enhancing antibiotic activity. More at eScienceCommons and at her lab’s site.

Posted on January 15, 2016 by Quinn Eastman in Uncategorized Leave a comment

Odd couples and persistence

When doctors treat disease-causing bacteria with antibiotics, a few bacteria can survive even if they do not have a resistance gene that defends them from the antibiotic. These rare, slow-growing or hibernating cells are called “persisters.”

Microbiologists see understanding persistence as a key to fighting antibiotic resistance and possibly finding new antibiotics. Persistence appears to be regulated by constantly antagonistic pairs of proteins called toxin-antitoxins.

Basically, the toxin’s job is to slow down bacterial growth by interfering with protein production, and the antitoxin’s job is to restrain the toxin until stress triggers a retreat by the antitoxin. Some toxins chew up protein-encoding RNA messages docked at ribosomes, but there are a variety of mechanisms. The genomes of disease-causing bacteria are chock full of these battling odd couples, yet not much was known about how they work in the context of persistence.

Biochemist Christine Dunham reports that several laboratories recently published papers directly implicating toxin-antitoxin complexes in both persistence and biofilm formation. Her laboratory has been delving into how the parts of various toxin-antitoxin complexes interact.HigBA smaller

BCDB graduate student Marc Schureck and colleagues have determined the structure of a complex of HigBA toxin-antitoxin proteins from Proteus vulgaris bacteria via X-ray crystallography. The results were recently published in Journal of Biological Chemistry.

While Proteus vulgaris is known for causing urinary tract and wound infections, the HigBA toxin-antitoxin pair is also found in several other disease-causing bacteria such as V. cholera, P. aeruginosa, M. tuberculosis, S. pneumoniae etc.

“We have been directly comparing toxin-antitoxin systems in E. coli, Proteus and M. tuberculosis to see if there are commonalities and differences,” Dunham says.

The P. vulgaris HigBA structure is distinctive because the antitoxin HigA does not wrap around and mask the active site of HigB, which has been seen in other toxin-antitoxin systems. Still, HigA clings onto HigB in a way that prevents it from jamming itself into the ribosome.

Posted on December 10, 2013 by Quinn Eastman in Uncategorized Leave a comment