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

Clostridium difficile

Poop substitute effective vs C. diff

A pill derived from human feces can effectively ward off Clostridium difficile diarrhea, according to the results of a clinical trial published in the New England Journal of Medicine.

Clinical microbiologist/infectious disease specialist Colleen Kraft and Emory patients contributed to the Phase III, 182 patient study, which was sponsored by Seres Therapeutics. Kraft is associate chief medical officer at Emory University Hospital and 2022 president-elect of the American Society for Microbiology.

Colleen Kraft, MD

Seres’ pill is an alternative to fecal microbiota transplant (FMT), a treatment for C.difficile that is both well-established and difficult to standardize. Everyone is intimately familiar with the material necessary for FMT, but its microbial components vary with the individual donor, diet and time. That presents some inconsistency and risk that has delayed FDA approval for the procedure.

Moving toward an “off the shelf” product, Seres takes stool from prescreened donors and treats the material with ethanol, killing some microbes and leaving behind bacterial spores that can compete for intestinal real estate with C. difficile. A previous study of Seres’ pill was unsuccessful, inspiring the headline “Sham poo washes out.” More information about the newer study and the company’s plans are in this Science article.

C. difficile colonization sometimes occurs after antibiotics deplete healthier forms of intestinal bacteria. Kraft and colleagues at Emory have been investigating whether FMT can prevent colonization by antibiotic-resistant bacteria in kidney transplant patients, who have (deliberately) dampened immune systems and need to take antibiotics.

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FMT microbial transplant for C diff gaining acceptance

In February, the Infectious Diseases Society of America issued new guidelines for fighting Clostridium difficile, the hardy bacterium that can cause life-threatening diarrhea and whose dominance is sometimes a consequence of antibiotic treatment. The guidelines recommend for the first time that FMT (fecal microbiota transplant) be considered for individuals who have repeatedly failed standard antibiotics.

In a nice coincidence, Emory FMT specialists Colleen Kraft and Tanvi Dhere recently published a look at their clinical outcomes with C diff going back to 2012, in Clinical Infectious Diseases. They report 95 percent of patients (122/128) indicated they would undergo FMT again and 70 percent of the 122 said they would prefer FMT to antibiotics as initial treatment if they were to have a recurrence. Read more

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Measuring microbiome disruption

How should doctors measure how messed up someone’s intestinal microbiome is?

This is the topic of a recent paper in American Journal of Infection Control from Colleen Kraft and colleagues from Emory and the Centers for Disease Control and Prevention. The corresponding author is epidemiologist Alison Laufer Halpin at the CDC.

A “microbiome disruption index” could inform decisions on antibiotic stewardship, where a patient should be treated or interventions such as fecal microbial transplant (link to 2014 Emory Medicine article) or oral probiotic capsules.

What the authors are moving towards is similar to Shannon’s index, which ecologists use to measure diversity of species. Another way to think about it is like the Gini coefficient, a measure of economic inequality in a country. If there are many kinds of bacteria living in someone’s body, the disruption index should be low. If there is just one dominant type of bacteria, the disruption index should be high.

In the paper, the authors examined samples from eight patients in a long-term acute care hospital (Wesley Woods) who had recently developed diarrhea. Using DNA sequencing, they determined what types of bacteria were present in patients’ stool. The patients’ samples were compared with those from two fecal microbial transplant donors. Read more

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An effective alternative to fecal transplant for C. difficile?

Bacterial spores in capsules taken by mouth can prevent recurrent C. difficile infection, results from a preliminary study suggest.

Clostridium difficile is the most common hospital-acquired infection in the United States and can cause persistent, sometimes life-threatening diarrhea. Fecal microbiota transplant has shown promise in many clinical studies as a treatment for C. difficile, but uncertainty has surrounded how such transplants should be regulated and standardized. Also, the still-investigational procedure is often performed by colonoscopy, which may be difficult for some patients to tolerate.

The capsule study, published Monday in Journal of Infectious Diseases, represents an important step in moving away from fecal microbiota transplant as a treatment for C. difficile, says Colleen Kraft, MD, assistant professor of pathology and laboratory medicine and medicine (infectious diseases) at Emory University School of Medicine.

Kraft and Tanvi Dhere, MD, assistant professor of medicine (digestive diseases) have led development of the fecal microbiota transplant program at Emory. They are authors on the capsule study, along with investigators from Mayo Clinic, Massachusetts General Hospital, Miriam Hospital (Rhode Island), and Seres Therapeutics, the study sponsor.

While this study involving 30 patients did not include a control group, the reported effectiveness of 96.7 percent compares favorably to published results on antibiotic treatment of C. difficile infection or fecal microbial transplant. Read more

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C. difficile: its name says what it is

If you’re looking for an expert on the “notorious” bacterium Clostridium difficile, consider Emory microbiologist Shonna McBride.

C. difficile is a prominent threat to public health, causing potential fatal cases of diarrheal disease. C. difficile can take over in someone’s intestines after antibiotics clear away other bacteria, making it dangerous for vulnerable patients in health care facilities. Healthcare-associated infections caused by other types of bacteria such as MRSA have been declining, leaving C. difficile as the most common cause, according to recently released data from the CDC.

Shonna McBride, PhD

McBride’s work focuses on how C. difficile is able to resist antimicrobial peptides produced by our bodies that keep other varieties of bacteria in check.

A 2013 paper from her lab defines genes that control C. difficile’s process for sequestering these peptides. It appears that its ability to resist host antimicrobial peptides evolved out of a system for resisting weapons other bacteria use against each other.

Since C. difficile requires an oxygen-free environment to grow, studying it can be more difficult than other bacteria. The McBride lab has a recent “video article” in the Journal of Visualized Experiments explaining how to do so using specialized equipment.

McBride explains in a recent Microbe magazine cover article that C. difficile’s ability to form spores is connected to the threat it poses:

Without the ability to form spores, the strict anaerobe C. diffıcile would quickly die in the presence of atmospheric oxygen. However, the intrinsic resilience of these spores makes them diffıcult to eradicate, facilitating the spread of this pathogen to new hosts, particularly in health care settings where they withstand many of the most potent disinfectants.

Yet the process of sporulation is markedly different in C. difficile compared with other kinds of bacteria, she says in the review.

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