Gonorrhoea is the second most prevalent bacterial sexually transmittable infection (STI) worldwide. The bacterium Neisseria gonorrhoeae has developed resistance to all currently and previously recommended antibiotics used to treat it. In the first section of this thesis, we investigate the factors underpinning resistance in STI core-groups. We characterized the molecular pathways via which azithromycin resistance emerges in N. gonorrhoeae. In addition to the known macrolide resistance conferring mutations at the target binding site and the efflux pump, we discovered novel ribosomal protein mutations. We show that a population exposed to high levels of antibiotics due to frequent STI screening, has more resistant commensal Neisseria species in their throat compared to the general population. As commensal Neisseria species play an important role in the evolution of antimicrobial resistance in the pathogenic N. gonorrhoeae, including them in monitoring activities could serve as an early warning system. In the second section of this thesis, we evaluate new antibiotic sparing treatment options for gonorrhoea. Although we were unable to isolate bacteriophages effective against currently circulating N. gonorrhoeae strains, throat samples tested did exhibit antigonococcal activity. Bacteriocins, which could be promising alternatives to antibiotics and offer a novel strategy to prevent and treat gonorrhoeae infection, may be responsible for the observed lysis. Next, we assessed the consequences of using mouthwashes as alternative treatment. We report that chlorhexidine sensitivity might diminish after prolonged exposure, and even more concerning, it may cause cross-resistance to antibiotics currently used to treat gonorrhoea. Resistance to Listerine® could not be induced, but daily Listerine® use did influence the oropharyngeal microbiome. These findings imply that mouthwash applications may have unintended consequences and should be carefully considered.
Prof. dr. Chris Kenyon (ITM)
Prof. dr. Surbhi Malhotra-Kumar (University of Antwerp)
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