The binding of phthalates with nuclease influences the DNA enzymatic degradation

Abstract Extracellular DNA (exDNA) degradation determines the persistence and the dissemination of antibiotic resistance genes which are the root cause for antibiotic resistance threatened human health. However, the effect of ubiquitous environmental endocrine-disrupting chemicals such as phthalates (PAEs) on this process is unclear. Here, we investigated the DNA degradation in the presence of five typical PAEs [dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), bis(2-ethylhexyl) phthalate (DEHP), benzyl butyl phthalate (BBP)] via gel electrophoresis experiments, spectroscopic analyses, atomic force microscopy, and molecular dynamics simulations. Results show that the PAEs inhibited DNA enzymatic degradation. PAEs were bound to amino groups in deoxyribonuclease I (DNase I) amino acid residues via van der Waals forces and hydrogen bonding, leading to the decrease of helix structure and structural deformation of DNase I, which in turn caused the decrease of its enzymatic activity. This binding interaction mainly contributed to the inhibition of DNA degradation. The maximum inhibition rates of PAEs on DNase I enzymatic activity were up to 83% (DMP), 64% (DEP), 60% (DBP), 77% (DEHP), 88% (BBP), respectively. This work provides interesting insights into how coexistent toxic organic contaminants affect the environmental fate of genetic macromolecules and further reveals their molecular ecological effects.