[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
Meningococcal quinolone resistance originated from several commensal Neisseria species
Mingliang Chen, Chi Zhang, Xi Zhang, Min Chen
Quinolone resistance is increasing in Neisseria meningitidis, with high prevalence in China (>70%), but its origin remains unknown. The aim of this study was to investigate donors of mutation-harboring gyrA alleles in N. meningitidis. A total of 198 N. meningitidis and 293 commensal Neisseria isolates were collected between 2005 and 2018 in Shanghai, China. Minimum inhibitory concentrations (MICs) of ciprofloxacin were determined using agar dilution method. Resistance-associated genes gyrA and parC were sequenced for all isolates, while a few isolates were performed Illumina sequencing. The prevalence of quinolone resistance in N. meningitidis and commensal Neisseria was 67.7% (134/198) and 99.3% (291/293), respectively. All 134 quinolone-resistant N. meningitidis isolates possessed mutations in T91 (n=123) and/or D95 (n=12) of GyrA, with 7 isolates also harboring ParC mutations and exhibiting higher MICs. Phylogenetic analysis of the gyrA sequence identified six clusters. Among the 71 mutation-harboring gyrA alleles represented by 221 N. meningitidis isolates and genomes (n=221), 12 alleles (n=103, 46.6%) were included in N. meningitidis cluster, while 20 alleles (n=56) in N. lactamica cluster, 27 alleles (n=49) in N. cinerea cluster, and 9 alleles (n=10) in N. subflava cluster. Genomic analyses identified the exact N. lactimica donors of seven mutation-harboring gyrA alleles (gyrA92, gyrA97, gyrA98, gyrA114, gyrA116, gyrA151, and gyrA230) and the N. subflava donor isolate of gyrA171, with recombinant fragment ranging from 634 to 7499 bp. Transformation of gyrA 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 quinolone-resistant N. meningitidis isolates acquired resistance by horizontal gene transfer from three commensal Neisseria species. Quinolone resistance in N. meningitidis increases in a stepwise manner.
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Keywords: Antibiotics; Drugs Resistance; Neisseria meningitidis; Meningococcal meningitis; Quinolones.