Neisseria gonorrhoeae: antibiotic resistance, genomic changes and evolution

The emergence and global spread of multidrug resistant strains, most especially to antibiotics of choice in the treatment of gonorrhoea, limits treatment options and complicates disease management, making it a major global health concern hence efforts are needed to ensure gonorrhoea remains a treatable infection. The main aim of this research is to demonstrate and understand more about the mechanisms of N. gonorrhoeae antibiotic resistance with the view of determining ways to curb this menace. To fully expose the mechanisms of antimicrobial resistance, a more conclusive understanding of genome content across the Neisserial population is needed to comprehensively evaluate the evolution and mechanisms of antimicrobial resistance in this species.

Progressive mauve was used to analyse and compare the genome sequence of four distinct Neisseria species strains with the complete genome sequences of Neisseria gonorrhoeae, Neisseria meningitidis and the genomes of commensal Neisseria species including Neisseria subflava and Neisseria cinerea that are available in the NCBI Genbank database. Three of the Neisseria species strains were identified as Neisseria subflava while one was identified as Neisseria cinerea. The Neisseria species strains were found to be encapsulated. To improve the isolation of Neisseria species in the laboratory and most especially in the resource poor areas, the standard Oxoid GC, Chocolate and Thayer-Martin agars were modified with the addition of 0.75 g/l sodium bicarbonate (NaHCO3) with the modified GC media proving suitable for Neisseria species antimicrobial susceptibility testing. This was a novel finding and an alternative to atmospheric CO2 needed for growth of the bacteria. The ‘evolve and sequence’ experiment was used to evolve and identify key resistance mechanisms. This comparative genomics study provides insights into evolutionary adaptations and possibly host-pathogen interactions that contribute to disease manifestation and antibiotic resistance. Data including genes and their mutations were collated, meta-analysed and will be used to create a database where end users can input novel genome sequence data and generate in silico antimicrobial profiles.

This research has improved the knowledge of Neisseria species population biology, Neisseria species culture and antimicrobial resistance. The knowledge and results from this research will help in the development of new antimicrobial therapies, alternative diagnostic tests for Neisseria gonorrhoeae, tools to identify antimicrobial resistance, and other means of curbing Neisseria gonorrhoeae antimicrobial resistance.