Tag Archives: C diff research and developnent

C. diff. Research and Development – August 2015

Microbiota and Subsequent Effects on Colonization Resistance against Clostridium difficile

Alyxandria M. Schubert, Hamide Sinani, Patrick D. Schloss

To read this paper in its entirety :

http://mbio.asm.org/content/6/4/e00974-15.short?rss=1&ssource=mfr

The gastrointestinal tract harbors a complex community of bacteria, known as the microbiota, which plays an integral role preventing its colonization by gut pathogens. This resistance has been shown to be crucial for protection against Clostridium difficile infections (CDI), which are the leading source of hospital-acquired infections in the United States. Antibiotics are a major risk factor for acquiring CDI due to their effect on the normal structure of the indigenous gut microbiota. We found that diverse antibiotic perturbations gave rise to altered communities that varied in their susceptibility to C. difficile colonization. We found that multiple coexisting populations, not one specific population of bacteria, conferred resistance. By understanding the relationships between C. difficile and members of the microbiota, it will be possible to better manage this important infection.

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The spore-associated protein BclA1 affects the susceptibility of animals to colonization and infection by Clostridium difficile

To read this paper in its entirety :

http://onlinelibrary.wiley.com/doi/10.1111/mmi.12611/abstract

The paper shows that so-called “hypervirulent” strains of C. difficile, such as the 027 ribotype strains, are actually less infectious than the existing strains of C. difficile carried in humans and animals. We were able to show this by characterizing one gene of C. difficile that encodes the BclA1 protein. BclA1 is involved in the early stages of colonization and its presence enables spores of C. difficile to colonise the host. When this protein is removed or truncated the ability of spores to colonise is much reduced. This then raises the question of how hypervirulent strains are more efficient at infecting a host, in other words, how they can be more virulent. The answer is probably the hypervirulent strains are able to produce more toxins. This work raised the concept that C. difficile is similar to influenza. For example, with influenza the most infectious influenza strains  do not normally cause fatality (ie, the seasonal flu strains). On the other hand, the pandemic strains (avian influenza) are not very infectious (that is, they spread poorly) yet when they do infect they cause a dangerous infection more likely to lead to fatality. C. difficile we reason behaves in a similar way, the hypervirulent strains are poorly infectious yet cause a more potent infection while highly infectious strains cause a less potent infection. We plan to use this knowledge to type new isolates of C. difficile and assess their risk to humans.

Professor Simon M. Cutting
School of Biological Sciences,
Bourne Laboratories, 4-26,
Royal Holloway, University of London
Egham,
Surrey TW20 OEX
UK

C. diff. cases higher in the Spring according to a study conducted by researchers at the University of Texas at Austin

People may be more likely to get infected with the sometimes deadly gut infection called “C. diff” during the spring, according to a new study.

Researchers analyzed information from people who were discharged from U.S. hospitals between 2001 and 2010. During this time period, about 2.3 million people were released from a hospital following an infection with Clostridium difficile, which can cause severe diarrhea, and frequently comes back after treatment.

In the spring, there were about 62 cases of C. difficile for every 10,000 people discharged from the hospital, the study found.

In winter and summer, there were 59 C. difficile cases per 10,000 people discharged from the hospital, and the lowest rate was seen in the fall, when there were 56 C. difficile cases per 10,000 hospital discharges.

Most cases of C. difficile occur after people take antibiotics, which disturb the normal balance of gut bacteria, giving harmful bacteria the chance to overgrow. It’s possible that the rates of C. difficile infection are the highest in the spring because people use more antibiotics during the winter months to treat respiratory infections, the researchers said. There can be a one- to two-month lag between the time a person takes antibiotics, or antimicrobials, and when he or she develops a C. difficile infection.

The new finding “emphasizes the importance of antimicrobials’ use as a risk factor” for                   C. difficile infections, the researchers said. The results also underscore the need to better control infections and use antibiotics only when they are needed,” particularly during high-risk seasons and in high-risk areas, the researchers wrote.

The study also found that, over the 10-year study period, the rates of C. difficile infection were the highest in the Northeast, where the overall rate was 80 cases per 10,000 hospital discharges, followed by the Midwest (64 cases per 10,000 hospital discharges), the South (50 cases per 10,000 hospital discharges) and the West (48 cases per 10,000 hospital discharges).

These regional differences in C. difficile could be partly due to differences in the number of older adults in each area, with the Northeast possibly having a higher proportion of older adults, the researchers said. Older adults are at increased risk for C. difficile infection. In fact, the overall rate of C. difficile infections during the study was 160 cases per 10,000 hospital discharges among adults age 65 and older, compared with 35 cases per 10,000 discharges in adults under 65 and 12 cases per 10,000 discharges in children.

“Our findings indicate the need for additional resources when and where health care burdens are highest,” the researchers said.

The study, conducted by researchers at the University of Texas at Austin, is published in the May issue of the American Journal of Infection Control.

 

To read article in its entirety click on the following link:

http://news.yahoo.com/deadly-gut-bacteria-infections-peak-spring-145430313.html;_ylt=A0LEVxPSvkNV1ooA0MFXNyoA;_ylu=X3oDMTEza2t0ajNjBGNvbG8DYmYxBHBvcwMxBHZ0aWQDVklQNTY0XzEEc2VjA3Nj

Dr Casey Theriot and Dr Martha Clokie Join The C Diff Foundation To Discuss Their Latest Scientific Research On C diff Radio

Key scientific researchers join the                        C Diff Foundation to discuss their latest scientific research:

Dr. Casey Theriot of University of Michigan will be discussing the latest research how         C. difficile wreaks havoc on the guts of animals in a short time and causes severe diarrhea and life-threatening diseases in humans.

 

 

Dr. Matha Clokie of University of Leicester, UK will also be discussing her most recent work in the area of C. difficile research; ‘Bacteria-eating viruses ‘magic bullets in the war on superbugs’

“C. diff. Spores and More” spotlights world renown topic experts, research scientists, healthcare professionals, organization representatives, C. diff. survivors, board members, and their volunteers who are all creating positive changes in the C. diff. community and more. Through their interviews, the CDF mission will connect, educate, and empower many in over 180 countries.

C. diff. Spores and More airs live on Tuesdays at the following times:

ET   2 – 3 p.m.,  CT 1 – 2 p.m.,  MT 12 – 1 p.m.,  PT 11 – 12 p.m.

Join us Tuesdays in listening to the educational episodes.

For radio information and access episodes available to listen as a podcast please click on the link below:

www.voiceamerica.com/show/2441/c-diff-spores-and-more

 

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C Diff Foundation Welcomes Dr. David Cook, Ph.D.

We are pleased to welcome

Dr. David Cook,Ph.D.

joining the C Diff Foundation’s Research and Development Committee and Research Community.

David Cook is a scientist and entrepreneur who has held senior operating and management positions in the biotechnology industry over his 20-year career. Before joining Seres Health, he was the chief operating officer for the International AIDS Vaccine Initiative (IAVI), a global R&D organization whose mission is to develop a safe, globally accessible vaccine for HIV. Prior to IAVI, David was the founding CEO at Anza Therapeutics, a biotechnology start-up developing a novel microbial vaccine platform to induce cellular immune responses to fight or prevent diseases such as cancer, hepatitis C, malaria and tuberculosis. Before launching Anza, David held positions of increasing responsibility at the biotechnology corporations Cerus and Eligix, with oversight over R&D, program management, manufacturing, and clinical and regulatory affairs. He has led teams to develop and commercialize several biotech products and has been directly responsible for obtaining marketing authorization from the European Union for four novel medical products. He is also a co-inventor on over twenty-five patents. He received his undergraduate degree from Harvard College and his Ph.D. in chemistry from the University of California, Berkeley.

C. diff. Research and Development Community; November/December 2014

Here’s the latest from the

C. diff. Research Community:

 

 
Animal models of Clostridium difficile infection (CDI) are essential for the better understanding of this disease. The historical animal model for studying CDI was the Golden Syrian hamster, and the murine model for CDI has been described by Dr. Ciaran Kelly’s group in 2008. In this current study, Koenigsknecht et al. have used the antibiotic-treated murine model to describe in great detail the early dynamics of CDI in mice from ingestion and colonization, germination and colitis.
http://iai.asm.org/content/early/2014/12/16/IAI.02768-14.long

 

The role of host microbiota in the development of C. diff. infection (CDI) has been studied in great detail. In the current issue of Cell Host Microbe, two studies have looked at two different pathogens and their interactions with host microbiota.

In the first study, by Ferreyra et al, the authors show that following antibiotic treatment                 C. difficile uses host microbiota produced succinate to colonize the gut and cause diarrhea.

In the second study, Curtis et al. show that Bacteroides thetaiotaomicron enhances the expression of virulence genes of enterohemorrhagic Escherichia coli (EHEC) leading to EHEC colonization. B.thetaiotaomicron leads to increased levels of succinate which in turn is sensed by transcription factor Cra, which then leads to the enhanced expression of virulence genes in EHEC.

Although commensal microbiota often prevents pathogens from gaining a foothold in the gut by providing colonization resistance, gut pathogen have evolved in ways so that they can exploit metabolites produced by commnesals to use for their own advantage.

http://ac.els-cdn.com/S1931312814004193/1-s2.0-S1931312814004193-main.pdf?_tid=6ff3eb40-8f91-11e4-b02e-00000aab0f6b&acdnat=1419881733_d475a24b936814a7c30ed35c6ffeffb7
http://ac.els-cdn.com/S1931312814004211/1-s2.0-S1931312814004211-main.pdf?_tid=b1cc6540-8f93-11e4-a2e9-00000aab0f6b&acdnat=1419882703_c8e4440013034567236b8bf782708315

 

Several journal articles in December have been published looking at the efficacy of LFF571 in treateing CDI. LFF571 is a novel semi-synthetic thiopeptide antibacterial that inhibits bacterial protein synthesis.

The first article includes results from a Phase 2 exploratory study where the authors compared the safety and efficacy (based on a non-inferiority analysis) of LFF571 to vancomycin in adults with primary episodes or first recurrences of moderate C. difficile. Results show that based on protocol-specified definition, rates of clinical cure for LFF571 were non-inferior to those of vancomycin, recurrences were lower for LFF571 and LFF571 was generally safe and well-tolerated.
The second article compares the pharmacokinetics (PK) of LFF571 and vancomycin in patients with  a C. difficile infection (CDI) as part of an early efficacy study. Patients were randomized to receive 200 mg of LFF571 or 125 mg of vancomycin four times daily for 10 days. The highest LFF571 serum concentration was 41.7 ng/mL. This is in comparison to peak vancomycin serum level at 2.73 μg/mL. CDI patients had high fecal concentrations and low serum levels of LFF571 which is similar to healthy volunteers.
http://aac.asm.org/content/early/2014/12/16/AAC.04251-14.long
http://aac.asm.org/content/early/2014/12/16/AAC.04252-14.long

 

 

Chandrabali Ghose-Paul,MS,PhD, Chairperson of C. diff. Research and Development