Infectious proteins found in bacteria

Prions are infectious agents comprised of proteins that can fold in many ways and still be functional. They cause other, normal proteins to fold into their “prion version,” often causing disease, as observed in eukaryotic organisms. Collectively, prion diseases are called transmissible spongiform encephalopathies and affect the brain and nervous system. Mad-cow disease – a rapid degeneration of the brain, is a well-known example of a disease caused by these self-propagating proteins. In addition, prions are suspected to play a role in Alzheimer’s disease through the formation of amyloid-beta plaques, or clusters of proteins, in the brain.

Until recently, prions were thought to be unique to eukaryotic cells. However, researchers at Harvard Medical School have shown their existence in bacteria. A protein in Clostridium botulinum was shown to act like a prion when inserted into other host bacteria and yeast.

The protein was discovered while scanning the genomes of thousands of bacteria for prion-forming proteins in yeast. While specifically looking at Rho proteins, which are involved in the regulation of gene expression, they found one such potential prion forming a Rho protein in C. botulinum. This section was inserted into Escherichia coli upon which the proteins folded in ways similar to prions, as observed by the forming of protein clumps. These proteins were then injected into yeast where they again caused normal proteins to fold incorrectly and multiply, thus spreading the infection.

In addition to its normal activity in E. coli, the Rho protein suppress multiple genes from being expressed; however, many of these genes were active when the protein folded into its prion form. This suggested that prions could be advantageous to bacteria in adapting to environmental stresses. One such observed adaptation was E. coli survival after being exposed to ethanol. Prions have previously been shown to be heritable, thus bacteria could inherit traits that would allow colonies to withstand stressful environments without genetic mutation, which could have implications to antibiotic resistance.

Additionally, if the Rho protein can be shown to act as a prion in a natural host, then this would allow bacteria to be used to study the behavior of prions for Alzheimer’s and Parkinson’s disease research, both of which are thought to be linked to prions.