The recombination efficiency of the bacterial integron depends on the mechanical stability of the synaptic complex | Science Advances

Multiple antibiotic resistances are a major global health threat. The predominant tool for adaptation in Gram-negative bacteria is the integron. Under stress, it rearranges gene cassettes to offer an escape using the tyrosine recombinase IntI, recognizing folded DNA hairpins, the attC sites. Four recombinases and two attC sites form the synaptic complex. Yet, for unclear reasons, the recombination efficiency varies greatly. Here, we established an optical tweezers force spectroscopy assay to probe the synaptic complex stability and revealed, for seven combinations of attC sites, significant variability in the mechanical stability. We found a strong correlation between mechanical stability and recombination efficiency of attC sites in vivo, indicating a regulatory mechanism from the DNA structure to the macromolecular complex stability. Taking into account known forces during DNA metabolism, we propose that the variation of the integron in vivo recombination efficiency is mediated by the synaptic complex stability. We anticipate that further recombination processes are also affected by their corresponding mechanical stability.