Interactions between antibiotics and heavy metals determine their combined toxicity to Synechocystis sp

Co-pollution of antibiotics and metals is prevailing in aquatic environments. However, risks of coexisted antibiotics and metals on aquatic organisms is unclear. This study investigated the combined toxicity of antibiotics and metals towards Synechocystis sp. PCC 6803, a cyanobacterium. We found that the joint toxicity of antibiotics and metals is dependent on their interplays. The complexation between chlortetracycline (CTC) and copper/cadmium (Cu(II)/Cd(II)) resulted in their antagonistic toxicity. Contrarily, an additive toxicity was found between florfenicol (FLO) and Cu(II)/Cd(II) due to lack of interactions between them. CTC facilitated the intracellular uptake of Cu(II) and Cd(II) by increasing the membrane permeability. However, FLO had no obvious effects on the internalization of metals in Synechocystis sp. Proteomic analysis revealed that the photosynthetic proteins was down-regulated by CTC and FLO, and ribosome was the primary target of FLO. These results were verified by parallel reaction monitoring (PRM). Cu(II) induced the up-regulation of iron-sulfur assembly, while Cd(II) disturbed the cyclic electron transport in Synechocystis sp. The co-exposure of CTC and metals markedly alleviated the dysregulation of proteins, while the co-exposure of FLO and metals down-regulated biological functions such as ATP synthesis, photosynthesis, and carbon fixation of Synechocystis sp., compared with their individuals. This supports their joint toxicity effects. Our findings provide better understanding of combined toxicity between multiple pollutants in aquatic environments.