Antimicrobial Resistance in Neisseria gonorrhoeae Studies

The global rise of antimicrobial resistance in Neisseria gonorrhoeae presents a critical challenge to public health and clinical practice. Historically treated with penicillin and tetracycline, gonorrhoea therapy evolved through fluoroquinolones to cephalosporins and dual regimens incorporating azithromycin. However, the bacterium’s remarkable capacity to acquire resistance through target-site mutations, acquisition of mosaic alleles and upregulation of efflux pumps has undermined these regimens. Resistance determinants such as mosaic penA alleles reduce susceptibility to extended-spectrum cephalosporins, while mutations in ribosomal genes and interspecies recombination of efflux pump components confer macrolide resistance. Whole-genome sequencing has revealed the clonal expansion of resistant lineages and the international spread of high-risk clones. Surveillance data highlight geographic variation in resistance prevalence, with azithromycin resistance plateauing at high levels in many regions, and sporadic but concerning reports of treatment failures to ceftriaxone. The paucity of new antimicrobials for gonorrhoea underscores the urgent need for strengthened surveillance, judicious antimicrobial stewardship, and the development of rapid diagnostic tests to guide individualised therapy. Insights from structural biology into regulator–ligand interactions and population genomics of resistance mechanisms are guiding novel therapeutic strategies and informing the search for a gonococcal vaccine.

Research from Nature Portfolio

Recent studies have illuminated how host-derived hormones modulate gonococcal resistance. Structural and biochemical analyses reveal that the transcriptional repressor of the MtrCDE efflux pump binds physiological steroids such as progesterone and oestradiol at infection sites. Steroid binding alters the conformation of the repressor, reducing its DNA affinity and de-repressing efflux pump expression. This mechanism links hormonal milieu to enhanced expulsion of multiple antimicrobials and provides the first atomic-level view of ligand-induced activation of a gonococcal resistance regulator. The insights suggest that local host factors can drive transiently elevated resistance, with implications for treatment efficacy in different anatomical niches and for the design of efflux pump inhibitors.

Antimicrobial Resistance in Neisseria gonorrhoeae Studies publication trend

The graph below shows the total number of articles in antimicrobial resistance in neisseria gonorrhoeae studies across all publications each year (not limited to Nature Index journals).

Technical terms

Efflux pump: A membrane-embedded protein complex that actively exports antimicrobial agents out of the bacterial cell, reducing intracellular drug concentration.

Mosaic allele: A gene variant composed of segments derived from different strains or species through recombination, often conferring novel resistance traits.

Minimum inhibitory concentration (MIC): The lowest concentration of an antimicrobial that prevents visible growth of a microorganism under standardized laboratory conditions.

Whole-genome sequencing: A laboratory method that determines the complete DNA sequence of an organism’s genome, enabling comprehensive analysis of resistance determinants and phylogenetic relationships.

References

1. Hormonal steroids induce multidrug resistance and stress response genes in Neisseria gonorrhoeae by binding to MtrR. Nature Communications (2024).
2. Antimicrobial-resistant Neisseria gonorrhoeae in Europe in 2020 compared with in 2013 and 2018: a retrospective genomic surveillance study. The Lancet Microbe (2024).
3. WHO global antimicrobial resistance surveillance for Neisseria gonorrhoeae 2017–18: a retrospective observational study. The Lancet Microbe (2021).
4. Azithromycin Resistance through Interspecific Acquisition of an Epistasis-Dependent Efflux Pump Component and Transcriptional Regulator in Neisseria gonorrhoeae. mBio (2018).