Navigation Links
New defense discovered against common hospital-acquired infection

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
University of Texas Medical Branch at Galveston

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:
(Date:11/24/2015)... York, N.Y. (PRWEB) , ... November 24, 2015 , ... ... Giving Tuesday, the global movement driven by social media and the generosity of people ... Speaks, then encourage their social media networks to give – and share the personal ...
(Date:11/24/2015)... Tennessee (PRWEB) , ... November 24, 2015 , ... ... Pharmacy Quality Trend Report . Throughout the past year there have been multiple breakthroughs ... mature state. During this transition, PharmMD has enabled their customers and partners to stay ...
(Date:11/24/2015)... San Mateo, CA (PRWEB) , ... November 24, 2015 , ... “I am so thrilled, ... teacher Stephanie Lederman after learning she had won a $7,500 School Lounge Makeover® from ... Chandler, Arizona, where most of the staff has a much longer tenure. , “This is ...
(Date:11/24/2015)... ... November 24, 2015 , ... Add a fresh touch ... an easy and affordable way to bring long-lasting style and cheer to any space. ... oxygen, clean the air and keep on giving all year long. , “Holiday plants ...
(Date:11/24/2015)... ... ... Tudore Tranquility is a new restaurant in Tokyo, Japan that recently opened their ... is full of flavorful and creative dishes that exceed expectations. It is an elegant ... intimate event. The décor looks stunning with gold and beige tones. , Tudore ...
Breaking Medicine News(10 mins):
(Date:11/24/2015)... 24, 2015 Teledyne DALSA , a Teledyne ... technology, will introduce its CMOS X-Ray detector for mammography ... 29 to December 3, at McCormick Place in ... diagnostic and interventional imaging will be on display in the ... of advanced CMOS X-Ray detectors is the industry benchmark for ...
(Date:11/24/2015)... , Nov. 24, 2015  Enova Illumination is ... of Helsinki, Finland to combine ... are at the cutting edge of medical visualization: Enova ... the United States and Novocam ... Together, they provide the world,s most powerful battery-operated LED ...
(Date:11/24/2015)... Nov. 24, 2015  Freudenberg Medical has developed specialty tubing ... outside of medical facilities. Africa ... care is sparse. Nevertheless, prompt diagnosis is important to treat ... the virus. With the help of a portable mini-lab or ... to village in affected areas and perform rapid testing for ...
Breaking Medicine Technology: