Navigation Links
New defense discovered against common hospital-acquired infection
Date:8/21/2011

GALVESTON Researchers have discovered a key mechanism used by intestinal cells to defend themselves against one of the world's most common hospital-acquired bacterial infections a mechanism they think they can exploit to produce a therapy to protect against the effects of the antibiotic-resistant bacteria.

The scientists made their discovery while investigating cellular responses to two powerful toxins generated by the bacteria Clostridium difficile, which can cause symptoms ranging from diarrhea to life-threatening bowel inflammation.

"About one percent of all hospital patients develop a C. difficile infection they're treated with antibiotics to the point that benign gut bacteria are knocked out, and because C. difficile is resistant to antibiotics it's able to proliferate," said University of Texas Medical Branch at Galveston associate professor Tor Savidge, lead author of a paper on the discovery to be published online Aug. 21 in Nature Medicine. "Then it releases these toxins that trigger colonic disease."

The toxins wreak havoc on cell structural proteins and biochemical communications networks, eventually killing the cell. But in order to do this damage, the toxins first have to get into the cell, and that means passing through the protective membrane that surrounds it.

It's there that Savidge and his collaborators a multidisciplinary team of researchers from UTMB, UCLA, Case Western Reserve University, Tufts University and the Commonwealth Medical College may have found a way to stop them.

On the molecular scale, C. difficile toxin proteins are quite large big enough that they have to "cleave" so that a smaller piece can slip through the membrane and into the cell. This cleavage is accomplished by a built-in molecular guillotine called a cysteine protease, which activates when the toxin encounters a molecule called InsP6 that is present at much higher levels inside the cell than outside.

"It's sort of like a sensor mechanism that detects when it's in a cell the toxins say, InsP6 is here, it's time to cleave," Savidge said. "But we've identified a previously unknown protective response that activates after the toxins have induced gut inflammation, in which the host uses a process called nitrosylation to shut down the cysteine protease and prevent cleavage."

A toxin that's unable to cleave stays stuck in the cell membrane, incapable of attacking the cell.

The researchers used test-tube, cell culture, patient specimens and animal model experiments, along with computer simulations of molecular interactions, to thoroughly explore this response and to successfully devise a way to mimic it for therapeutic purposes.

"Think of these toxins as missiles that the bacteria is producing to go off and detonate inside the cell," Savidge said. "One way to defend against missiles is to send out signals that trick them into either disarming their sensory mechanisms or get them to prematurely detonate."

Cell culture and mouse experiments demonstrated that a combination of GSNO (the nitrosylating agent and the "disarming" part of Savidge's analogy) and InsP6 (the "premature detonation" part) worked to prevent damage from C. difficile. In fact, the combination therapy worked so well that the team is now preparing to test it in a clinical trial sponsored by UTMB's Institute for Translational Sciences.

"Identification of new treatment modalities to treat this infection would be a major advance," said Dr. Charalabos Pothoulakis, director of UCLA's Inflammatory Bowel Disease Center and a co-author on the study. "If we are successful with this approach, we may be able to treat other bacterial diseases in a similar way."


'/>"/>

Contact: Jim Kelly
jpkelly@utmb.edu
409-772-8791
University of Texas Medical Branch at Galveston
Source:Eurekalert

Related medicine news :

1. Malaria parasites camouflage themselves from the immune defenses of expectant mothers
2. A new line of defense against sexual assault
3. Cooling system may build eggs natural defenses against salmonella
4. Intestinal cell defense mechanism against bacteria
5. US Department of Defense supports study of brain, eye injuries in military personnel
6. Feinstein Institute to share $5M US Department of Defense grant
7. NIH funds advanced development of 3 biodefense vaccines
8. Mice with human bodys defenses
9. Key leukemia defense mechanism discovered by VCU Massey Cancer Center
10. BU School of Medicine researcher receives Department of Defense award
11. Scripps and Trius team up to develop new antibiotics with US Department of Defense grant
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... Coveros, a ... has been awarded a contract by the Center for Medicare and Medicaid Services ... accelerate the enterprise use of Agile methodologies in a consistent and high value ...
(Date:10/12/2017)... (PRWEB) , ... October 12, 2017 , ... ... advisory services for healthcare compliance program management, will showcase a range of technology ... Association for Assisted Living (NCAL) Convention and Expo to be held October 14–18, ...
(Date:10/12/2017)... ... October 12, 2017 , ... The company has developed a ... and regulatory authorities worldwide. From Children’s to Adults 50+, every formula has been ... standard. , These products are also: Gluten Free, Non-GMO, Vegan, Soy Free, ...
(Date:10/12/2017)... ... October 12, 2017 , ... Asante, a nationally ... care, have expanded their existing home health joint venture through an agreement, effective ... operating a joint venture home health company with Asante, delivering clinically integrated care, ...
(Date:10/12/2017)... Malvern, PA (PRWEB) , ... October 12, 2017 , ... ... is the recipient of a 2017 Folio Magazine Eddie Digital Award for ‘Best ... New York City on October 11, 2017. , The annual award competition recognizes editorial ...
Breaking Medicine News(10 mins):
(Date:9/28/2017)... Hill-Rom Holdings, Inc. (NYSE: HRC), will host its fiscal ... Friday, November 3, 2017, beginning at 7:00 a.m. (CDT) ... a.m. (CDT) / 9:30 a.m. (EDT). In ... guidance for 2018, Hill-Rom executives will also highlight the ... long-range financial outlook through 2020. ...
(Date:9/27/2017)... and NEW YORK , Sept. 27, 2017 /PRNewswire/ ... health and big data solutions, today announced that its MyDario product is ... your local TV listings for when The Dr. Oz Show airs in ... The nine-time ... month. ...
(Date:9/23/2017)... Pa. , Sept. 22, 2017 Janssen ... a complete response letter from the U.S. Food and ... seeking approval of sirukumab for the treatment of moderately ... letter indicates additional clinical data are needed to further ... moderately to severely active RA. ...
Breaking Medicine Technology: