Lake Cadagno is characterised by a compact chemocline with high concentrations of purple sulfur bacteria (PSB). 2D-DIGE was used to monitor the global changes in the proteome of Candidatus "Thiodictyon syntrophicum" strain Cad16^T both in the presence and absence of light. This study aimed to disclose details regarding the dark CO₂ assimilation of the PSB, as this mechanism is often observed but is not yet sufficiently understood. Our results showed the presence of 17 protein spots that were more abundant in the dark, including three enzymes that could be part of the autotrophic dicarboxylate/4-hydroxybutyrate cycle, normally observed in archaea.