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

Reddit as window into opioid withdrawal strategies

Drug abuse researchers are using the social media site Reddit as a window into the experiences of people living with opioid addiction. Abeed Sarker in Emory's Department of Biomedical Informatics has a paper in Clinical Toxicology focusing on the phenomenon of “precipitated withdrawal,” in collaboration with emergency medicine specialists from Penn, Rutgers and Mt Sinai. Precipitated withdrawal is a more intense form of withdrawal that can occur when someone who was using opioids starts medication-assisted treatment Read more

CROI: HIV cure report and ongoing research

The big news out of CROI (Conference on Retroviruses and Opportunistic Infections) was a report of a third person being cured of HIV infection, this time using umbilical cord blood for a hematopoetic stem cell transplant. Emory’s Carlos del Rio gave a nice overview of the achievement for NPR this morning. As del Rio explains, the field of HIV cure research took off over the last decade after Timothy Brown, known as “the Berlin patient,” Read more

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 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 by Quinn Eastman in Uncategorized Leave a comment