Meningococcal Quinolone Resistance Originated from Several Commensal Neisseria Species

Quinolone resistance is increasing in , with its prevalence in China being high (>70%), but its origin remains unknown. The aim of this study was to investigate the donors of mutation-harboring alleles in A total of 198 isolates and 293 commensal isolates were collected between 2005 and 2018 in Shanghai, China. The MICs of ciprofloxacin were determined using the agar dilution method. The resistance-associated genes and were sequenced for all isolates, while a few isolates were sequenced on the Illumina platform. The prevalences of quinolone resistance in the and commensal isolates were 67.7% (134/198) and 99.3% (291/293), respectively. All 134 quinolone-resistant isolates possessed mutations in T91 ( = 123) and/or D95 ( = 12) of GyrA, with 7 isolates also harboring ParC mutations and exhibiting higher MICs. Phylogenetic analysis of the sequence identified six clusters. Among the 71 mutation-harboring alleles found in 221 isolates and genomes ( = 221), 12 alleles ( = 103, 46.6%) were included in the cluster, while 20 alleles ( = 56) were included in the cluster, 27 alleles ( = 49) were included in the cluster, and 9 alleles ( = 10) were included in the cluster. Genomic analyses identified the exact donors of seven mutation-harboring alleles ( , , , , , , and ) and the donor isolate of , with the sizes of the recombinant fragments ranging from 634 to 7,499 bp. Transformation of fragments from these donor strains into a meningococcal isolate increased its ciprofloxacin MIC from 0.004 μg/ml to 0.125 or 0.19 μg/ml and to 0.5 μg/ml with further transformation of an additional ParC mutation. Over half of the quinolone-resistant isolates acquired resistance by horizontal gene transfer from three commensal species. Quinolone resistance in increases in a stepwise manner.