Abstract
BackgroundNeisseria meningitidis (N.meningitidis) bacteria belonging to clonal complex 4821 (CC4821) have been mainly reported in China and have been characterized by a high resistance rate to ciprofloxacin (CIP). The aim of this study was to assess the evolution of the DNA gyrase A (gyrA) gene from N.meningitidis CC4821 strains collected in China between 1978 and 2016. The complete sequence of gyrA gene from 77 strains are reported in this study and analyzed in the context of publicly available sequences from N. meningitidis of other CCs as well as other Neisseria species.ResultsThe phylogenetic analysis of CC4821 gyrA gene reveals at least 5 distinct genetic clusters. These clusters are not CC4821-specific showing that gyrA evolution is independent of CC4821 evolution. Some clusters contain sequences from other Neisseria species. Recombination within N.meningitidis strains and between Neisseria species was identified in SimPlot analysis. Finally, amino acid substitutions within GyrA protein were analyzed. Only one position, 91 (83 in E.coli gyrA gene), was linked to CIP resistance. Thirty-one additional putative resistance markers were identified, as amino acid substitutions were only found in resistant strains.ConclusionsThe evolution of gyrA gene of CC4821 N.meningitidis strains is not dependent on CC4821 evolution or on CIP resistance phenotype. Only amino acid 91 is linked to CIP resistance phenotype. Finally, recombination inter- and intra-species is likely to result in the acquisition of various resistance markers, 31 of them being putatively mapped in the present study. Analyzing the evolution of gyrA gene within CC4821 strains is critical to monitor the CIP resistance phenotype and the acquisition of new resistance markers. Such studies are necessary for the control of the meningococcal disease and the development of new drugs targeting DNA gyrase.
Highlights
Neisseria meningitidis (N.meningitidis) bacteria belonging to clonal complex 4821 (CC4821) have been mainly reported in China and have been characterized by a high resistance rate to ciprofloxacin (CIP)
Evolutionary analysis of 77 gyrase A (gyrA) nucleotide sequences from CC4821 N.meningitidis strains Seventy seven de novo gyrA sequences of CC4821 N.meningitidis were analyzed in the context of 149 publicly available gyrA sequences
An overview of the tree showed that the sequences from CC4821 N.meningitidis strains were found across the tree demonstrating that gyrA gene was relatively divergent within these strains
Summary
Neisseria meningitidis (N.meningitidis) bacteria belonging to clonal complex 4821 (CC4821) have been mainly reported in China and have been characterized by a high resistance rate to ciprofloxacin (CIP). The complete sequence of gyrA gene from 77 strains are reported in this study and analyzed in the context of publicly available sequences from N. meningitidis of other CCs as well as other Neisseria species. Meningitis is an inflammation of the protective membranes covering the brain and the spinal cord (https:// www.cdc.gov/meningococcal). This disease can have multiple causes like bacteria or virus and fungus, parasite or even non-infectious agent like lupus. N.meningitidis are classified through several different schemes, based on serological test (serogroup) or genetic tests (sequence type) [2, 3]. The strains can be grouped into different sequence types (STs) based on the multilocus sequence typing (MLST) method on 7 genes (abcZ, adk, aroE, fumC, gdh, pdhC, pgm) [3]. The strains that could not be classified into an existing CC were called unassigned (UA)
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