Tag Archives: C. diff. Research Community

Researchers From North Carolina State University Find That Antibiotics Give C.diff. Nutrient-Rich Environment

Using a mouse model, researchers from North Carolina State University have found that antibiotic use creates a “banquet” for Clostridium difficile (C. diff), by altering the native gut bacteria that would normally compete with C. diff for nutrients. The findings could lead to the development of probiotics and other strategies for preventing C. diff infection.

C. diff is a harmful bacterium that can cause severe, recurrent and sometimes fatal infections in the gut. Although the bacteria are commonly found throughout our environment, C. diff infections primarily occur in patients who are taking, or who have recently finished taking, antibiotics.

“We know that antibiotics are major risk factors for C. diff infection because they alter the gut microbiota, or composition of bacteria in the gut, by eliminating the bacteria that are normally there,” says Casey Theriot, assistant professor of infectious disease at NC State and corresponding author of a paper describing the research. “Our latest work suggests that the microbiota may provide natural resistance to C. diff colonization by competing with C. diff for nutrients in that environment; specifically, for an amino acid called proline.”

Theriot and postdoctoral fellow Joshua Fletcher introduced C. diff to antibiotic-treated mice and monitored their gut environment at four intervals: 0, 12, 24, and 30 hours after introduction. They conducted metabolomic and RNA sequencing analysis of the gut contents and the C. diff at these time points to find out which nutrients the bacteria were “eating.” Metabolomics allowed the team to trace the abundance of the nutrients in the gut, and RNA analysis indicated which genes in the C. diff were active in metabolizing nutrients.

The researchers found that the amount of proline in the gut decreased as the population of C. diff increased. Additionally, the amount of a proline byproduct called 5-aminovalerate also increased, indicating that C. diff was metabolizing the proline. The RNA analysis further confirmed C. diff‘s use of proline, as genes related to proline metabolism in C. diff increased during the early stages of colonization, when proline was abundant.

“We’ve been able to show that in the absence of competition C. diff is metabolizing proline and other amino acids in the mouse model, using it as fuel to survive and thrive,” Theriot says. “Hopefully this information could lead to the development of better probiotics, or ‘good’ bacteria that can outcompete C. diff for nutrients in the gut. The ultimate goal is to control these bacteria in ways that don’t rely solely on antibiotics.”

To review article in its entirety please click on the following link to be redirected:

https://www.sciencedaily.com/releases/2018/03/180328204122.htm

Norman B. Javitt, M.D. Is Welcomed As a Member Of the C Diff Foundation, R & D Committee

We are pleased to welcome
Norman B. Javitt, M.D. to the
C Diff Foundation.

Dr. Javitt has an extensive professional career in health care.  New York University Medical Center: Instructor, then Assistant Professor Medicine where his career was devoted mostly to research in liver disease, specifically in inborn errors of cholesterol metabolism affecting newborns, and to teaching medical students.

Cornell University Medical School-New York Hospital:  Associate Professor of Medicine, then Professor of medicine and Chief, Division of Gastroenterology the research program continued to grow, attracting many fellows from all over the world.  Also provided care for private patients, both children and adults, with difficult liver problems.

New York University Medical Center:  Professor of Medicine and of Pediatrics, Division chairman Hepatic Diseases April, Research professor 2015-presnt.  At NYUMC Dr. Javitt has been focusing on C. difficile research  and teaching medical students and house staff.  His research interest has also expand to many areas of cholesterol synthesis and metabolism other than just liver disease.

Dr. Javitt has published research papers in age-related macular degeneration, in vitro fertilization, and Alzheimer’s disease.  He has also published more than 150 research papers, in addition to several books and review articles, and presented work at numerous professional meetings and symposia throughout the world.  His work has been supported by the National Institutes of Health, by private foundations and Pharmaceutical companies.  Dr. Javitt is welcomed by fellow researchers in the Research and Development Committee Chaired by Professor Simon M. Cutting, Ph.D…

Vitality Biopharma Researchers Unlock the Use of Cannabinoid Compounds For the Treatment of Microbes Including Clostridium difficile

Vitality Biopharma a corporation dedicated to the development of cannabinoid prodrug pharmaceuticals, and to unlocking the power of cannabinoids for the treatment of serious neurological and inflammatory disorders, today announced that it has obtained positive results demonstrating antimicrobial activity of cannabinoids and filed for patent protection on the use of cannabinoid compounds for the treatment of microbes including Clostridium difficile and other “superbug” pathogens.

Utilizing a list of the top drug-resistant pathogens from the United States Centers for Disease Control and Prevention (CDC), Vitality researchers screened for antimicrobial activity in their portfolio of compounds. Vitality Biopharma discovered new antimicrobial activities for cannabinoids, and as a result has filed for patent protection on the use of cannabinoids and cannabinoid prodrugs for the treatment of multiple pathogenic bacterial infections.

At the top of the CDC’s list is Clostridium difficile (C. diff), which is classified as an urgent threat to human health. The CDC reported in 2015 that it infected almost 500,000 Americans and was directly responsible for 15,000 deaths. Vitality successfully demonstrated antimicrobial reactivity of a cannabinoid against C. diff, and is currently conducting follow-on studies designed to enable pharmaceutical use of their targeted cannabinoid prodrugs for this application.

The Company also confirmed that cannabinoids have antimicrobial activity towards methicillin-resistant Staphylococcus aureus (MRSA), a pathogen that was recently listed on the World Health Organization’s (WHO) list of priority pathogens that pose a significant threat to human health globally. Additional antimicrobial activity was seen towards other antibiotic-resistant bacterial species that were included on the CDC and WHO lists, and Vitality is seeking broad intellectual property coverage for use of cannabinoids against these pathogens as well.

“Our cannaboside prodrugs enable the targeted delivery of cannabinoids into the large intestine, where C.diff infections colonize, take over, and can cause severe damage.  Our compounds are uniquely suited for performing this task, and it’s now clear they may provide benefits to gut health through multiple mechanisms.” said Dr. Brandon Zipp, Director of R&D at Vitality.  Robert Brooke, the Company’s CEO, adds that, “This is a logical extension of our work that has been focused on gastrointestinal disease, and represents a new opportunity to treat a serious and life-threatening condition.”

 

To read the article in its entirety, click on the link below:

http://www.dddmag.com/news/2017/05/vitality-biopharma-announces-positive-results-cannabinoid-antibiotics

Clostridium difficile Research Suggests That Positively Selected Sites In the Surface Layer Proteins May Play A Role In Driving the Emergence of Hyper-virulent Strains

  • Mark Lynch,
  • Thomas A. Walsh,
  • Izabela Marszalowska,
  • Andrew E. Webb,
  • Micheál MacAogain,
  • Thomas R. Rogers,
  • Henry Windle,
  • Dermot Kelleher,
  • Mary J. O’ConnellEmail author and
  • Christine E. Loscher

To Read Abstract/Article In Its Entirety Please Click On the Following Link:

https://bmcevolbiol.biomedcentral.com/articles/10.1186/s12862-017-0937-8

 

Abstract

Background

Clostridium difficile is a nosocomial pathogen prevalent in hospitals worldwide and increasingly common in the community.

Sequence differences have been shown to be present in the Surface Layer Proteins (SLPs) from different C. difficile ribotypes (RT) however whether these differences influence severity of infection is still not clear.

Results

We used a molecular evolutionary approach to analyse SLPs from twenty-six C. difficile RTs representing different slpA sequences. We demonstrate that SLPs from RT 027 and 078 exhibit evidence of positive selection (PS).

We compared the effect of these SLPs to those purified from RT 001 and 014, which did not exhibit PS, and demonstrate that the presence of sites under positive selection correlates with ability to activate macrophages.

SLPs from RTs 027 and 078 induced a more potent response in macrophages, with increased levels of IL-6, IL-12p40, IL-10, MIP-1α, MIP-2 production relative to RT 001 and 014. Furthermore, RTs 027 and 078 induced higher expression of CD40, CD80 and MHC II on macrophages with decreased ability to phagocytose relative to LPS.

Conclusions

These results tightly link sequence differences in C. difficile SLPs to disease susceptibility and severity, and suggest that positively selected sites in the SLPs may play a role in driving the emergence of hyper-virulent strains.