Tag Archives: C. diff. infection

Vanderbilt University Medical Center Scientists Demonstrated C. diff. Exposed To Heme Increases Expression of a Protein System Not Previously Studied

 

Vanderbilt University Medical Center scientists have identified a C. diff protein system that senses and captures heme (part of hemoglobin) to build a protective shield that fends off threats from our immune system and antibiotics. The findings, reported in the journal Cell Host & Microbe, reveal a unique mechanism for C. diff survival in the human gut and suggest novel strategies for weakening its defenses.

In a cruel twist, the bacterium Clostridioides difficile (C. diff) makes us bleed and then uses our blood to defend itself against us.

C. diff the most common cause of health care-associated infections (HAI’s) in the United States causes diarrhea and inflammation of the colon (colitis). Individuals taking antibiotics, which disturb the protective gut microbiota, have increased risk for acquiring a C. diff infection, and 20% of patients suffer recurrent C. diff infections despite treatment.

When C. diff colonizes the gut, it produces toxins that cause tissue damage and inflammation. Blood cells burst, releasing heme, the part of hemoglobin that binds iron and oxygen.

Eric Skaar, Ph.D., MPH, Ernest W. Goodpasture Professor of Pathology, Microbiology and Immunology, and colleagues have studied how bacteria respond to heme, which is both a source of the nutrient iron and a reactive, toxic compound.

“Organisms that experience large amounts of heme have to have ways to deal with heme toxicity,” said Skaar, director of the Vanderbilt Institute for Infection, Immunology and Inflammation (VI4). “We wanted to understand how C. diff deals with heme exposure.”

The investigators demonstrated that C. diff exposed to heme increases expression of a protein system that had not been previously studied. They named the system HsmRA (heme sensing membrane proteins R and A) and showed that HsmR senses heme and deploys HsmA to capture it. They also found that the HsmRA system is genetically conserved in many bacterial species.

The binding of heme in the bacterial membrane by HsmA serves a protective purpose first by simply reducing the concentration of free heme, Skaar explained. The researchers also discovered that HsmA uses heme binding to protect C. diff from oxidative stress, including that produced by neutrophils and macrophages from our immune system to kill bacteria.

“C. diff is using cofactors from our own cells as a shield to protect against our innate immune response,” Skaar said.

Oxidative stress also plays a role in antibiotic action.

“Antibiotics have different molecular targets—they may prevent cell wall synthesis; they may prevent protein translation—but the net result of that stress on the cell is often the massive accumulation of oxidative stress that many believe to be a major contributor to why antibiotics kill bacteria,” Skaar said.

The investigators studied whether the HsmRA system protected C. diff against antibiotics.

“We found a really impressive phenotype with vancomycin and metronidazole, two of the front-line antibiotics used to treat C. diff,” Skaar said. “C. diff that expresses HsmA, when HsmA is bound to heme, is much more resistant to vancomycin and metronidazole.”

They also showed that C. diff strains with inactivated HsmR or HsmA had reduced colonization in a mouse model of relapse C. diff infection.

Skaar said it has not been clear why C. diff produces toxins that cause so much tissue damage.

“It’s interesting to speculate that a benefit of toxin-related damage is that C. diff can capture liberated heme and use it as a shield to protect itself against various insults that cause oxidative stress—that would be immune cells, antibiotics and potentially other bacteria.”

The findings suggest that targeting the HsmA-heme shield might increase the sensitivity of C. diff to antibiotics such as vancomycin and metronidazole. It’s not clear that HsmA, a membrane protein, will be a druggable target, Skaar said.

It might be possible, however, to deprive C. diff of heme building blocks by reducing tissue damage or by administering proteins that bind heme, he said. The researchers will explore whether they can increase the sensitivity of C. diff to antibiotics by co-administering a heme-binding protein during infection in an animal model.

“We’re excited about this as a potentially powerful strategy for treating C. diff,” Skaar said.

In other studies, the researchers will explore if the HsmRA system that is genetically conserved in many different organisms has the same functional role to protect against reactive oxygen species. They are also trying to understand the exact mechanism that HsmA-heme uses to detoxify oxidative stress.

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

https://phys.org/news/2020-06-clostridioides-difficile-captures-blood-cell.html

C. difficile Infection (C. diff.); A Survivor’s Perspective with CDI Introduction by Teena Chopra, MD,MPH,FACP,FIDSA,FSHEA

Join us on Tuesday, May 26th at 1:00 p.m. EST

C. diff. Spores and More Live Broadcast

www.cdiffradio.com

With Doctor Teena Chopra, MD,MPH,FACP,FIDSA,FSHEA
Associate Professor of Medicine,Division of Infectious Diseases,
Corporate Medical Director,Infection Prevention,Epidemiology,and Antibiotic Stewardship ,DMC and WSU Director,Infection Prevention,Epidemiology and Antibiotic Stewardship,Vibra Hospital

Dr. Chopra will lead the discussion with an overview of a C. difficile infection followed by Alba Muhlfeld, and Renata Johnson, C. diff. Survivors both sharing their journey and providing
key-points to our global listeners.

Unable to listen to the live broadcast?

Access the C. diff. Spores and More Library
http://www.cdiffradio.com
and listen at your leisure.

 

 

C. diff. Spores and More is sponsored by

C Diff Foundation Members Are Here For YOU Especially During the Pandemic

To Our Dear Patients, Families, and Healthcare Professionals,

To say these times have been trying is a giant understatement. We hope that you and your families are staying safe during this period of self quarantine, social distancing and limiting your daily exposures to help flatten the curve of COVID-19.

If anything is to come of this, we hope that it will be the value of hand washing, which will in turn help to prevent the spread of Healthcare-associated infections (HAI’s).

COVID-19 is in the forefront and this pandemic has majorly changed our lives. We are living through this together while healthcare professionals, across the globe, are dedicated  in developing the best possible practices for infection prevention, treatments and safety in public health.  For up-to-date COVID-19 information, please visit the CDC website:  www.cdc.gov

Be rest assured that the C Diff Foundation members continue to work diligently to educate and advocate for C. diff.  Infection prevention,  treatments, clinical trials, diagnostics, environmental safety and support to help those diagnosed with, being treated for, and recovering from a
C. diff. Infection worldwide.

Should you find yourself needing assistance with C. diff. infection information and support, please do not hesitate to contact us. We are here for you, your families, friends and healthcare professionals to see you through, and beyond a C. diff. infection.

A huge thank you goes out from all of us here at the C Diff Foundation to the brave men and women on the front lines of this pandemic. Without you and your bravery,  we would be in a major state of disarray. Thank you for being a guiding light for us all worldwide.

Check in on your neighbors, friends and families to make sure that they are okay. Keep your spirits high and know that we will get through this together.

“None of us can do this alone ~ All of us can do this together.”

C Diff Foundation Members Are Here For YOU Even During the Pandemic

To Our Dear Patients, Families, and Healthcare Professionals,

To say these times have been trying is a giant understatement. We hope that you and your families are staying safe during this period of self quarantine, social distancing and limiting your daily exposures to help flatten the curve of COVID-19.

If anything is to come of this, we hope that it will be the value of hand washing, which will in turn help to prevent the spread of Healthcare-associated infections (HAI’s).

COVID-19 is in the forefront and this pandemic has majorly changed our lives. We are living through this together while healthcare professionals, across the globe, are dedicated  in developing the best possible practices for infection prevention, treatments and safety in public health.  For up-to-date COVID-19 information, please visit the CDC website:  www.cdc.gov

Be rest assured that the C Diff Foundation members continue to work diligently to educate and advocate for C. diff.  Infection prevention,  treatments, clinical trials, diagnostics, environmental safety and support to help those diagnosed with, being treated for, and recovering from a
C. diff. Infection worldwide.

Should you find yourself needing assistance with C. diff. infection information and support, please do not hesitate to contact us. We are here for you, your families, friends and healthcare professionals to see you through, and beyond a C. diff. infection.

A huge thank you goes out from all of us here at the C Diff Foundation to the brave men and women on the front lines of this pandemic. Without you and your bravery,  we would be in a major state of disarray. Thank you for being a guiding light for us all worldwide.

Check in on your neighbors, friends and families to make sure that they are okay. Keep your spirits high and know that we will get through this together.

“None of us can do this alone ~ All of us can do this together.”

C Diff Foundation with Leading Gastroenterologist’s Oneto and Feuerstadt Announce November Clinic Dedicated for C.difficile

C Diff Foundation ( https://cdifffoundation.org/)  is a one hundred percent volunteer, world-renowned 501(c)(3) not-for-profit organization and has announced that the Foundation will offer a November clinic sponsored by the C Diff Foundation and dedicated to patients diagnosed and recovering from a C. difficile infection (CDI).

The November 19th C Diff Foundation Clinic will be hosted by Concorde Gastroenterology at their  233 Broadway Suite 840,  New York, NY 10279 office.
The clinic will hold office hours from 10:00 a.m. until  4:00 p.m. ET
With Doctor’s Caterina Oneto, MD and  Paul Feuerstadt, MD

Please call +1 212 889 5544 Ext 199
To schedule an appointment.

The August clinic received an overwhelming response from patients in various stages of recovery, including 15 individuals already scheduled with multiple spots planned for patients with recently diagnosed infection or those who have had multiple episodes and need further guidance and management.

Dr. Oneto said, “Through this clinic, we will provide access to high-level care to a number of new consults, as well as existing patients, who are recovering from the infection. It is my pleasure to partner with the C Diff Foundation and lend my expertise to the management and hopefully, eradication of this debilitating disease.”

“We are delighted with the immediate and overwhelming response from the patient community. It is a testament to the needs of those suffering from this infection. With this clinic, we hope to bring awareness, education and more importantly, cutting edge treatment to the general public,” stated Dr. Feuerstadt.

There are plans for additional clinic dates in 2020  in Florida, New York, Connecticut, Illinois, and Minnesota.

“The clinics demonstrate Doctor Oneto and Feuerstadt’s commitment over the years raising
C. diff. awareness while providing management of those suffering with
a C. diff. infection. Patients who might not otherwise be able to gain access to providers sub-specializing and caring for those with this infection will have this opportunity available.  Doctor’s Oneto and Feuerstadt’s dedication resonates within the C. diff. community and we are grateful for their participation and support.” stated Nancy Caralla, Founding President and Executive Director of the C Diff Foundation.

About C Diff Foundation

C Diff Foundation’s mission is dedicated to reaching out to communities from villages to cities, to medical practitioners, medical students, C. diff. survivors, caregivers, and the patients combating a C. difficile infection (CDI) while providing the general public important information on prevention, treatments available, clinical trials in progress, nutrition, diagnostics, and EPA registered products available for environmental safety worldwide.

About Caterina Oneto, MD

Dr. Caterina Oneto, MD is a Gastroenterologist in private practice in New York and is affiliated with NYU Langone. She completed her Fellowship in Gastroenterology at Montefiore Medical Center, Albert Einstein College of Medicine. Dr. Oneto is the Co-Director of Clinical trials at Concorde Medical Group. Her main focus is Irritable Bowel Disease (IBD),

About Paul Feuerstadt, MD

His areas of interest Clostridioides difficile infection (CDI) and ischemic diseases of the gut and in these areas he has presented his research extensively, authored and co-authored many manuscripts, textbook chapters, and online modules. Another passion of Dr. Feuerstadt is teaching, frequently giving lectures locally, regionally and nationally. He holds a clinical appointment as an Assistant Clinical Professor of Medicine at the Yale University School of Medicine and is a full-time attending physician at the Gastroenterology Center of Connecticut seeing patients with a broad spectrum of clinical gastroenterological diseases.

Dr. Feuerstadt attended the Weill Medical College of Cornell University in Manhattan for medical school and completed his residency in internal medicine at New York-Presbyterian Hospital/Weill Cornell. His clinical fellowship training was completed at Montefiore Medical Center in the Bronx, New York.

Clostridioides difficile infections (AKA C. diff., C.difficile, CDI) and Microbiome modification.
Dr Oneto is also Co-Director of the C.diff. Community Global Support program offered by the
C Diff Foundation.  Dr. Oneto appears regularly on Doctor Radio on Sirius Xm
and C. diff. Spores and More Radio (cdiffradio.com).

About C.difficile

It is the most common Healthcare-associated infection affecting an estimated 450,000 people annually in the United States alone with ~28,000 deaths from complications of this infection. This infection accounts for ~16% of all healthcare-associated infections.

In the USA: Nearly half a million Americans suffer from Clostridioides difficile (C. diff.) infections in a single year according to a study released on February 25, 2015, by the Centers for Disease Control and Prevention (CDC).

**Approximately 29,000 patients died within 30 days of the initial diagnosis of C. difficile. Of those, about 15,000 deaths were estimated to be directly attributable to C. difficile infections (CDI), making C. difficile a very important cause of infectious disease death in the United States alone. More than 80 percent of the deaths associated with C. difficile occurred among Americans aged 65 years or older. C. difficile causes an inflammation of the colon and deadly diarrhea.