Antibiotic-induced recombination in Gram-negative bacteria requires the formation of double-strand breaks

Recombination is an essential process in bacterial drug resistance evolution. Fluoroquinolones, an important class of antibiotics, are known to stimulate recombination in Escherichia coli. When bacteria are exposed to antibiotics other than fluoroquinolones, including strong up-regulators of recombination pathways, there is no detectable change in the recombination level. Here we explore why fluoroquinolones, but not other antimicrobials, increase recombination rates. Fluoroquinolones, in contrast to other antibiotics, generate DNA double-strand breaks (DSBs). We tested whether other drugs that also cause double-strand breaks, such as mitomycin C and bleomycin, also affect bacterial recombination rates with consistent increases in recombination. A positive correlation between the number of DSBs and the recombination frequency was found. The manipulation of the level of DSBs directly impacted the recombination frequency. Our results highlight that only antibiotics that induce DNA double-strand breaks are more probable to increase genetic diversity via recombination. The stimulation of recombination by DSB-causing antimicrobials is an additional factor leading to the risk of antibiotic resistance evolution.