Introduction to the TSE

Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and goats, chronic wasting disease (CWD) in deer and elk, transmissible mink encephalopathy (TME) in farmed mink and bovine spongiform encephalopathy (BSE) in cattle (known as 'mad cow disease) are a group of fatal brain infections. The transmissible agent or agents of these diseases have not been definitively identified.

SpiroplasmaNGWe do know there is a filterable pathogen, since experimental transmission of these diseases can be prevented by a 35.nanometer filter, therein presumably ruling out most bacteria. The transmissible agent is resistant to heat, radiation and chemicals such as glutaraldehyde, unlike any known conventional virus. The only consistent findings in TSE are 1) a protease-resistant amyloid protein derived from a host protein (prion), and 2) scrapie-associated fibrils (named for their discovery in scrapie-affected animals). These proteins have become surrogate markers of the transmissible spongiform encephalopathies (TSE).

Our studies show a tiny bacterium is involved in the pathogenesis of TSE. Since the discovery of spiroplasma inclusions in CJD brain tissues in 1976, we have confirmed the consistent presence of spiroplasma ribosomal DNA in TSE tissues. DNA sequence data show a link between spiroplasma in CWD and in scrapie. Spiroplasma have been isolated into cell free media from TSE brain and eye specimens confirming the association of this bacterium with TSE. Spiroplasma inoculated into rodents and ruminants produce spongiform encephalopathy and a clinical syndrome remarkably similar to naturally occurring TSE. Recent discovery of biofilm formation by spiroplasma on glass, MICA and stainless steel supports the concept of a bacterial etiology. It is noteworthy that the internal fibril structure of spiroplasma is morphologically identical to SAF.

Spiroplasma entrapped in biofilm are protected from physical and chemical treatments, and not detected by the immune system, therein simulating the biologic properties of the TSE agent. Long conjugate interconnections between organisms in the biofilm suggest a mechanism wherein spiroplasma may form microcolonies in soil. Soil consumption by ruminants is likely responsible for lateral transmission of CWD. Sessile spiroplasma in biofilm produce a functional amyloid that may form a nidus for triggering prion amyloid formation. Continued accumulation of prion amyloid in TSE-affected brains likely occurs by self-assembly. Unfortunately this phenomenon has been interpreted as evidence of protein replication.

The discovery of involvement of spiroplasma in the pathogenesis of TSE opens many doors to 1) development of reliable diagnostic tests, 2) new strategies for treatment including antibiotics, and 3) finally getting some insight into the epidemiology of this elusive pathogen.