Bacterial DNA induces the formation of heat-resistant disease-associated proteins in human plasma

Our study demonstrated for the first time that bacterial extracellular DNA (eDNA) can change the thermal behavior of specific human plasma proteins, leading to an elevation of the heat-resistant protein fraction, as well as to de novo acquisition of heat-resistance. In fact, the majority of these proteins were not known to be heat-resistant nor do they possess any prion-like domain. Proteins found to become heat-resistant following DNA exposure were named “Tetz-proteins”. Interestingly, plasma proteins that become heat-resistant following treatment with bacterial eDNA are known to be associated with cancer. In pancreatic cancer, the proportion of proteins exhibiting eDNA-induced changes in thermal behavior was found to be particularly elevated. Therefore, we analyzed the heat-resistant proteome in the plasma of healthy subjects and in patients with pancreatic cancer and found that exposure to bacterial eDNA made the proteome of healthy subjects more similar to that of cancer patients. These findings open a discussion on the possible novel role of eDNA in disease development following its interaction with specific proteins, including those involved in multifactorial diseases such as cancer.