Navigation Links
Bacterial toxin closes gate on immune response, Penn researchers discover

PHILADELPHIA Researchers at the University of Pennsylvania School of Medicine have demonstrated that a bacterial toxin from the common bacterium Staphylococcus aureus shuts down the control mechanism of the tunnel, called an ion channel, in immune cell membranes. Shutting down ion channels has long been known to suppress the immune response, and the bacteria may use the toxin to neutralize host defenses against bacteria. The study is published in the February 14 issue of Nature.

Immune cells, like other cells, have ion channels in their membranes. When the voltage-sensing part of the channel detects an electrical change in the cell membrane, the channel gate opens, allowing small ions such as sodium, potassium, or calcium to flow across the cell membrane. The channels in immune cells called Kv1.3 channels allow only potassium ions to pass, and the activity of these channels is required for triggering an immune response.

We have provided a key piece of evidence for the hypothesis that the negatively charged phosphate groups of membrane lipids around voltage sensors provide the critical electric balance for some of these positive charges in the sensors, says Zhe Lu, MD, PhD, of the Department of Physiology at Penn. The research team, that included Yanping Xu, MD, PhD and Yajamana Ramu, PhD, showed that removal of phosphate head groups from some membrane lipids by the bacterial toxin called sphingomyelinase (SMase) C shuts down the Kv1.3 channel. Therefore if the positive charges are not properly balanced by negative charges, the electrical sensor cannot move to open the gate of the channel. And, if the channel fails to open, the immune response is derailed.

Our study builds on the efforts of two senior colleagues in the Department, says Lu. Twenty-five years ago, Professor Clay Armstrong (now emeritus) hypothesized that the positive charges in the electrical sensor must be balanced by negative charges for the sensor to function properly. And a few years later, Professor Carol Deutsch, among others, demonstrated the presence of potassium channels controlled by voltage in immune cells.

SMase C is made by, among other bacteria, S. aureus, a pathogenic bacterium that causes a range of infections from minor skin lesions to toxic shock. This finding raises the intriguing possibility that the SMase C action against Kv1.3 helps S. aureus to neutralize host defenses, state the authors in the paper.

The findings of this study suggest the possibility that identifying inhibitors of SMase C may be a way to combat S. aureus infections. One strain of S. aureus is the much-talked-about, MRSA, or methycillin-resistant S. aureus. Specific inhibitors of SMase C may expand the choice of therapies for treating MRSA and other resistant S. aureus infections.

This study was conducted in a common experimental system where frog eggs were engineered to have particular voltage-gated ion channels in their membranes. SMases used in the study were purified from bacteria engineered to produce the enzymes.

This new study follows a 2006 study by the same research team showing that an SMase from the brown recluse spider could activate voltage-gated ion channels. In 2007 the team discovered that SMases from lung-infecting bacteria inactivate ion channels that conduct chloride ions, which would in turn aggravate lung infection in some cystic fibrosis patients.


Contact: Karen Kreeger
University of Pennsylvania School of Medicine

Related medicine news :

1. Nerites Receives NIH Grant to Study Novel Treatment for Preventing Dangerous Bacterial Infections on Urinary Stents and Catheters
2. Forsyth launches 1-of-a-kind core service to enable rapid identification of bacterial samples
3. First look at an enzyme target for antibacterial and cancer drugs
4. Breath test can discriminate between a bacterial overgrowth and IBS
5. Antibacterial chemical disrupts hormone activities
6. GenPrime Initiates External Clinical Trials of its Bacterial Contamination Test for Rapid Detection of Bacteria in Platelets
7. Early Bacterial Infection May Boost Asthma Risk
8. New viruses to treat bacterial diseases -- My enemies enemy is my friend
9. Antibacterial Soap Claims Just Dont Wash
10. New study suggests link between environmental toxins and early onset puberty in girls
11. Botulinum Toxin Share Higher in Canada Than in the US
Post Your Comments:
(Date:11/24/2015)... ... 2015 , ... With Thanksgiving right around the corner, holiday travel season is ... your family and vehicle. , According to the National Highway Traffic Safety Administration, 301 ... sharing the following safety tips from the NHTSA: , ...
(Date:11/24/2015)... ... November 24, 2015 , ... Abington Hospital – Jefferson Health ... Quality® Bariatric Surgery Facility for treating individuals living with morbid or extreme obesity. ... available to its members to help them make informed decisions about their healthcare ...
(Date:11/24/2015)... ... November 24, 2015 , ... Sir Grout of Baltimore ... TrustDale certification. The award recognizes good companies for excellence in service and a ... grout, and hard surface restoration company earned this recognition after a thorough review ...
(Date:11/24/2015)... ... 24, 2015 , ... Autism Speaks, the world’s leading autism science and advocacy ... and the generosity of people around the world. On December 1, supporters can make ... – and share the personal stories behind those gifts. , Just as Black ...
(Date:11/24/2015)... ... , ... All her life, Don Peck’s mother wondered if she was a descendant of Samuel ... After a 25-year search for information, Don and his aunt discovered that she was ... Turns out, it was Don’s father who was descended from not one, but four ...
Breaking Medicine News(10 mins):
(Date:11/24/2015)... , Nov. 24, 2015  Thanks to a donor ... St. Mary,s Medical Center,s Sister Diane Grassilli Center for ... capabilities in San Francisco . ... friend, stepped forward with a gift of $617,320 that ... Digital Mammography with Tomosynthesis and Whole Breast Ultrasound. Tomosynthesis, ...
(Date:11/24/2015)... 2015 /PRNewswire/ - ESSA Pharma Inc. ("ESSA" or the ... that the first patient has been enrolled in ESSA,s ... for metastatic castration-resistant prostate cancer ("mCRPC"). ... --> the United States and ... clinical trial, ESSA intends to demonstrate the safety, tolerability, ...
(Date:11/24/2015)... --> --> ... by Product Type (Bone Graft, Bine Graft Substitute, Platelet Rich ... Lumbar Interbody Fusion), End User, and Geography - Global Forecast ... at $1.90 Billion in 2014 and is expected to reach ... the forecast period of 2015 to 2020. Browse ...
Breaking Medicine Technology: