Precision medicine with multiple myeloma

“Precision medicine” is an anti-cancer treatment strategy in which doctors use genetic or other tests to identify vulnerabilities in an individual’s cancer subtype. Winship Cancer Institute researchers have been figuring out how to apply this strategy to multiple myeloma, with respect to one promising drug called venetoclax, in a way that can benefit the most patients. Known commercially as Venclexta, venetoclax is already FDA-approved for some forms of leukemia and lymphoma. Researchers had observed that multiple Read more

Promiscuous protein droplets regulate immune gene activity

Biochemists at Emory are achieving insights into how an important regulator of the immune system switches its function, based on its orientation and local environment. New research demonstrates that the glucocorticoid receptor (or GR) forms droplets or “condensates” that change form, depending on its available partners. The inside of a cell is like a crowded nightclub or party, with enzymes and other proteins searching out prospective partners. The GR is particularly well-connected and promiscuous, and Read more

Neutrophils flood lungs in severe COVID-19

In the lungs of severe COVID-19 patients, neutrophils camp out and release inflammatory cytokines and tissue-damaging Read more

David Weiss

Combo approach vs drug-resistant fungus

Before 2020 and the COVID-19 pandemic, concern among infectious disease specialists was rising about Candida auris, an emerging fungal pathogen that is often drug-resistant and difficult to eradicate from hospitals.

CDC image of Candida auris

Many people know Candida can cause mouth or vaginal infections and diaper rashes. According to the CDC, Candida also can cause invasive infections in the bloodstream, particularly in hospital or nursing home patients with weakened immune systems. About 30 percent of patients with an invasive Candida infection die – and C. auris is just one particularly hardy variety.

Emory Antibiotic Resistance Center director David Weiss and colleagues have identified a combination of existing antifungal drugs (micafungin and amphotericin B) with enhanced activity against C. auris when used together. The results – in vitro only, so far — were published in a letter to The Lancet Microbe. Postdoctoral fellow Siddharth Jaggavarapu was the first author. Weiss reports his team continues to investigate combination approaches against C. auris.

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Focus on antibiotic resistance at ASM Microbe 2018

We are excited that the ASM Microbe meeting will be at the Georgia World Congress Center from June 7 to June 11. If you are interested in antibiotic resistance, you can learn about how to detect it, how to (possibly) defeat it and how the bacteria fight back.

A host of Emory microbiologists are participating. In some cases, our scientists are presenting their unpublished data for discussion with their colleagues at other universities. Accordingly, we are not going to spill the beans on those results. However, please find below some examples of who’s talking and a bit of explanatory background. ASM Microbe abstracts are available online for posters, but not for some symposiums and plenary talks.

David Weiss labKlebsiella

Graduate student Jessie Wozniak is presenting her research on an isolate of Klebsiella that combines alarming properties. She will describe how the bacterial colonies behave (unappetizingly) like stretchy melted cheese in a “string test.”

June 9, 11 am to 1 pm, June 11, 11 am to 1 pm

Christine Dunham – toxin-antitoxin/persistence

Graduate student Sarah Anderson presenting her poster at ASM Microbe. She discussed a genetic connection between virulence switch and antibiotic resistance.

Dunham, a structural biologist, is giving a plenary talk June 11 on toxin-antitoxin pairs, which play a role in regulating bacterial persistence, a dormant state that facilitates antibiotic resistance. Two past papers from her lab.

Phil Rather labAcinetobacter baumannii

Rather’s lab recently published a Nature Microbiology paper on A. baumannii’s virulence/opacity switch. This type of bacteria is known for hospital-associated infections and for wound infections in military personnel. Poster talk by graduate student Sarah Anderson June 8. Read more

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Retaining the resistance: MCR-1, colistin + lysozyme

If you’ve been following the news about antibiotic resistant bacteria, you may have heard about a particularly alarming plasmid: MCR-1. A plasmid is a circle of DNA that is relatively small and mobile – an easy way for genetic information to spread between bacteria. MCR-1 raises concern because it provides bacteria resistance against the last-resort antibiotic colistin. The CDC reports MCR-1 was found in both patients and livestock in the United States this summer.
David Weiss, director of Emory’s Antibiotic Resistance Center, and colleagues have a short letter in The Lancet Infectious Diseases showing that MCR-1 also confers resistance to an antimicrobial enzyme produced by our bodies called lysozyme. MCR-1-containing strains were 5 to 20 times less susceptible to lysozyme, they report.
This suggests that the pressure of fighting the host immune system may select for MCR-1 to stick around, even in the absence of colistin use, the authors say.
While the findings are straightforward in bacterial culture, Weiss cautions that there is not yet evidence showing that this mechanism occurs in live hosts. For those that really want to get alarmed, he also calls attention to a recent Nature Microbiology paper describing a hybrid plasmid with both MCR-1 and resistance to carbapenem, another antibiotic.

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Fooling the test: antibiotic resistant bacteria that look susceptible

A diagnostic test used by hospitals says a recently isolated strain of bacteria is susceptible to the “last resort” antibiotic colistin. But the strain actually ignores treatment with colistin, causing lethal infections in animals.

Through heteroresistance, a genetically identical subpopulation of antibiotic-resistant bacteria can lurk within a crowd of antibiotic-susceptible bacteria. The phenomenon could be causing unexplained treatment failures in the clinic and highlights the need for more sensitive diagnostic tests, researchers say.

In Nature Microbiology (published online Monday, May 9), scientists led by David Weiss, PhD, describe colistin-heteroresistant strains of Enterobacter cloacae, a type of bacteria that has been causing an increasing number of infections in hospitals around the world.

“Heteroresistance has been observed previously and its clinical relevance debated,” Weiss says. “We were able to show that it makes a difference in an animal model of infection, and is likely to contribute to antibiotic treatment failures in humans.”

Weiss is director of the Emory Antibiotic Resistance Center and associate professor of medicine (infectious diseases) at Emory University School of Medicine and Emory Vaccine Center. His laboratory is based at Yerkes National Primate Research Center. The co-first authors of the paper are graduate students Victor Band and Emily Crispell.

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