Zoliflodacin and gepotidacin cross-resistance in Neisseria gonorrhoeae

Resistance to zoliflodacin, a first-in-class antibiotic for gonorrhea treatment, can occur through gyrB ^D429N , but this mutation’s impact on fitness and resistance to other topoisomerase targeting drugs, including gepotidacin, have been unclear. Here, we show that gyrB ^D429N confers cross-resistance to gepotidacin in some clinical isolates and that its fitness effect varies with strain back-ground. These findings inform strategies for introducing the new topoisomerase inhibitors into clinical use and for surveillance of resistance.