Neisseria gonorrhoeae has demonstrated remarkable ability to rapidly develop antimicrobial resistance to each antimicrobial class used for therapy including the currently recommended class of antimicrobials, the cephalosporins. Emerging resistance to cephalosporins will severely complicate treatment of gonorrhoea. Advanced Molecular Detection approaches, such as whole genome sequencing to determine mechanisms of resistance, have the potential to advance our understanding of gonorrhoea. To date, we have sequenced >1,000 genomes from N. gonorrhoeae isolates with elevated cefixime or azithromycin minimum inhibitory concentrations (MICs) or resistance to previously recommended antimicrobials, and isolates collected from multiple geographic sites to accomplish the following objectives: (1) to identify mutations that confer antimicrobial resistance or increased MICs; (2) to inform the development of molecular assays for resistance determinants through insights gleaned from WG from which point-of-care assays for resistance markers will be developed. Such assays will change the paradigm of gonorrhoea treatment. Use of real-time results on the presence or absence of resistance determinants will allow clinicians to personalise treatment for patients, and prevent inadvertent use of agents that are no longer routinely recommended because of resistance. Such assays can also substantially expand the reach of surveillance of antimicrobial resistance and allow public health officials to rapidly detect and respond to outbreaks of resistant strains; and (3) to develop and maintain a microbial library, a web-accessible and searchable database that will include bacterial and viral genomic sequences and associated meta-data, such as basic de-identified demographic characteristics of patients and phenotypic susceptibility data. In the long term, knowledge of the genetic mechanisms responsible for resistance or deceased susceptibility in N. gonorrhoeae gained from sequencing may translate into the identification or development of new therapeutic agents.
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