BORRELIABAKTEERIN TUOTTAMA MYRKKY

[Bb]

Lähettäjä: Soijuv Lähetetty: 7.3.2006 9:12

Uusi mielenkiintoinen artikkeli borrelioosista ja borreliabakteerin tuottamasta botuliinin kaltaisesta myrkystä joka vaikuttaa nimenomaan hermosolujen toimintaan. Myrkky kuuluu metalloproteaaseihin.


Kok artikkeli: http://www.townsendletter.com/FebMar2006/lyme0206.htm

Introduction
The history of science has presented some unusual twists and turns in man's quest for knowledge. One researcher working quietly in one part of the world may unwittingly be solving another researcher's problem in another location. As we shall see in greater detail, government researchers and others, in an effort to combat future bio-terrorist attacks, have unknowingly contributed greatly to Lyme disease research.

A discovery of great importance relating to a toxin produced by the causative agent of Lyme disease, Borrelia burgdorferi, has been linked to a similar toxin produced by the organism Clostridium botulinum. The toxicity of these and other related substances is so great that bio-terrorists have long considered using them in terrorist attacks throughout the world. Anthrax and its spores are only one among many of such candidate organisms. For this reason, US government scientists and others are compelled to learn as much as possible about these highly dangerous toxins in an effort to develop antagonists against their fatal action. It is remarkable that the research to combat possible future bio-terrorist attacks may be applied directly to therapeutic protocols for Lyme disease. A description of these toxins and their biological activity is presented below, along with a listing of therapeutic substances that may be applied in the treatment of Lyme disease.

In 1982, the agent responsible for Lyme disease was discovered by Willy Burgdorfer, who isolated spirochetes belonging to the genus Borrelia from the mid-guts of ticks infecting deer, other wild animals, and dogs. Spirochetes are spiral-shaped bacteria of very early origin in the evolutionary scheme. The causative organism was named Borrelia burgdorferi (Bb), after its discoverer. Since then, the number of reports of Lyme disease have increased so dramatically that, today, Lyme disease is the most prevalent tick-borne illness in the United States (carried by fleas, mites, mosquitoes, and ticks).

Lyme Disease Toxin
Because many of the symptoms of Lyme disease involve the nervous system, it was speculated that the spirochete produced a toxin that disrupted normal nerve function. Through the use of DNA manipulations and a database of known protein toxin DNA sequences, a match was made with a selected Borrelia burgdorferi (Bb) gene and a specific toxin in the database. Protein generated from this cloned Bb gene was examined biochemically and found to have characteristics similar to that of botulinum, the toxin of Clostridium botulinum, a zinc endoproteinase.1

The toxin from Bb belongs to a family of toxic proteins known as "zinc endoproteinases" or metalloproteases, and includes the toxin from the organism causing tetanus as well as those from many other well-known infectious diseases. The structures of this family of toxins are all very similar, as determined by x-ray crystal analysis.2 They all contain zinc and perform the same proteolytic function, namely, cleaving the chemical (covalent) bond between two specific amino acids in a particular protein found in nerve cells.3 The substrate for this enzyme is very large, implying that any inhibitor of enzyme activity blocking the entry of the substrate into the active site must also be very large.

One reason for learning the structure of the toxin (including the active site) is to determine the geometry of this site, the exact positions of the atoms that bind other atoms in the substrate. Knowing the arrangement of these atoms permits the development of inhibitors of the toxin, substances that compete with the normal substrate for active site occupancy.4

Action of Toxin
The action of botulinum (as well as the toxin from the Lyme spirochete) is to prevent, through its action as a proteolytic enzyme, the release of the neurotransmitter acetylcholine. Nerve endings may be associated with other nerves or muscles (the neuromuscular junction). To understand this mechanism in greater detail, consider the basic principles of nerve physiology described below.............