Understanding and preventing the genesis of antibiotic resistance in Neisseria gonorrhoeae

There is real possibility that Neisseria gonorrhoea may become untreatable in the near future and that this resistance will emerge in men who have sex with men (MSM). Understanding the reasons underpinning the emergence of this resistance could facilitate efforts to prevent pan-resistance. We hypothesize that NGs extraordinary ability to mutate in the setting of dense sexual networks and extensive antibiotic usage in contemporary MSM sexual networks plays an important role in the genesis of resistance. We plan to test this hypothesis by developing an NG-morbidostat - a dynamic in-vitro model of NG resistogenicity. The morbidostat will be used to assess the molecular pathways towards resistance to ceftriaxone - the cornerstone of current treatment regimens. We will then assess if DNA extracts from the pharyngeal and rectal microbiomes of MSM recently treated with ceftriaxone/azithromycin can accelerate the acquisition of resistance when added to the NG-morbidostat model. DNA sequencing will be used to confirm that the acceleration was due to NG transformation. The findings will be used to provide evidence of the viability of a larger project we are developing that aims to prevent and combat antimicrobial resistance in N. gonorrhoea.