Monday Micro – A bacterial link to Multiple Sclerosis?

By Siouxsie Wiles 21/10/2013


OAlogo

Today marks the start of International Open Access Week, a global event now entering its sixth year, aimed at encouraging wider participation in Open Access – that is, making the results of research freely & immediately available online, and giving others the right to use and re-use those results as needed.

There were a number of possible stories to write about for this week’s Monday Micro, but in keeping with the spirit of Open Access week I have chosen one from a paper published in PLOS One, an Open Access journal. The paper describes, for the first time, the isolation of a strain of the bacterium Clostridium perfringens type B from a human – a woman presenting with symptoms of Multiple Sclerosis (MS) (1).

According to Wikipedia, MS is an inflammatory disease in which damage to the insulating covers of nerve cells in the brain and spinal cord disrupts the ability of parts of the nervous system to communicate. This disruption results in a wide range of symptoms, which may be physical, mental, or psychiatric, including visual dysfunction, incoordination and spastic paralysis. The cause of MS is not clear and there is no cure, with treatment aimed at improving function after an attack and preventing new attacks.

Clostridium perfringens is a Gram-positive, spore-forming bacterium related to C. botulinum and C. difficile. It is divided into a number of types which differ with regard to the toxins they carry. Type A carries the alpha toxin and is a common cause of food poisoning in humans, whereas types B and D carry the epsilon toxin (ETX), and are often carried in the gastrointestinal (GI) tracts of ruminant animals. The ETX is a protoxin converted to its active form in the GI tract by trypsin and chymotrypsinor or by a protease carried by C. perfringens. The active toxin is ~1,000 time more potent than the protoxin. In ruminants, once produced ETX is absorbed via the intestine, enters the blood stream and permeabilises the blood-brain barrier causing MS-like symptoms.

In their paper, Rumah and colleagues describe isolating C. perfringens type B from a woman with symptoms of MS (1). Furthermore, they investigated the GI carriage of C. perfringens in a population of MS patients and healthy controls, finding the type A strain present in about half of the healthy controls but less than a quarter of the MS patients. Next they analysed tissue bank blood and cerebrospinal fluid samples, and found that samples from MS patients were 10 times more likely to react to ETX than samples from healthy controls, suggesting that the immune systems of the MS patients had encountered ETX before (1).

So could this bacterial toxin be a cause of MS? Given its ability to cross the blood-brain barrier, and to cause MS-like symptoms in animals, this looks like a distinct possibility.

Reference:

1. Rumah KR, Linden J, Fischetti VA, Vartanian T (2013) Isolation of Clostridium perfringens Type B in an Individual at First Clinical Presentation of Multiple Sclerosis Provides Clues for Environmental Triggers of the Disease. PLoS ONE 8(10): e76359. doi:10.1371/journal.pone.0076359