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

Abstract Our study demonstrated for the first time that bacterial extracellular DNA (eDNA) can change the thermal behaviour 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 and 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 progression. Therefore, we analysed 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.