Wednesday 27 September 2023

New partnership seeks to reduce toxic effects of pathogenic digestive bacteria



The bacterium Clostridioides difficile is a nosocomial infectious agent and one that is challenging to treat. C. difficile infection is spread by bacterial spores found within faeces. Transmission occurs if surfaces become contaminated with the spores with further spread occurring via the hands of healthcare workers.




Mohamed Seleem, director of the Center for One Health Research, and the company Nectagen Inc,. have received a $275,000 grant from the U.S. National Institute of Allergy and Infectious Diseases. The funds will be used to study whether synthetic proteins developed by Nectagen can reduce the toxicity of the digestive bacteria.


The widespread use of antibiotics for a variety of medical issues can destroy beneficial intestinal biomes along with harmful infectious bacteria. The use of systemic antibiotics, including broad-spectrum penicillins/cephalosporins, fluoroquinolones, and clindamycin, causes the normal microbiota of the bowel to be altered.


This can open the door for spores of C. difficile to vegetate and dominate the digestive system, becoming a dangerous pathogen that can lead to life-threatening bouts of intestinal cramps and diarrhoea.


Other risk factors involved in the causation of infection include advanced age, chemotherapy, use of proton pump inhibitors, chronic renal disease, chronic liver disease, and malnutrition.

Only one new antibiotic drug has been developed to fight C. difficile in the past 40 years. Some patients are treated with an antitoxin, but it must be taken intravenously and is often prohibitively expensive. Currently, restoring the gut microflora through methods such as fecal microbiota transplantation is one of the most effective approaches for the treatment of an infection.


C. difficile recurs in up to 20 percent of patients after treatment, and many of those patients die. A more effective, less expensive, orally consumable approach is needed to reduce mortality from C. difficile.


The grant funding will enable the Seleem Lab in the Center for One Health Research — a collaborative effort of the Virginia-Maryland College of Veterinary Medicine and the Edward Via College of Osteopathic Medicine — to conduct testing on animal models to determine if synthetic “nanoCLAMP” proteins produced by Nectagen, ingested orally, can reduce the toxic effects of C. difficile.


The term nanoCLAMP contains the prefix “nano”, implying microscopic size; while CLAMP stands for CLostridal Antibody Mimetic Proteins. This refers to specialized molecules designed to bind to specific molecular targets within cells.


Nectagen is a Lawrence, Kansas-based biotechnology company that develops and markets “antibody mimetic reagents,” or lab-created molecules that behave similarly to an antibody by imitating an antibody’s binding properties.


It is hoped that the nanoCLAMP proteins will be “thermally stable and protease resistant” enough to survive in the digestive tract and protect endothelial cells lining the intestines from C. difficile toxin damage.

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 Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (

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