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G-quadruplex motifs in Neisseria gonorrhoeae as anti-gonococcal targets

  • Applied Genetics and Molecular Biotechnology
  • Published:
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Abstract

Neisseria gonorrhoeae is an obligate human pathogen that causes gonorrhea and has shown a vast emergence of multidrug resistance in recent times. It is necessary to develop novel therapeutic strategies to combat this multidrug-resistant pathogen. The non-canonical stable secondary structures of nucleic acids, G-quadruplexes (GQs), are reported to regulate gene expressions in viruses, prokaryotes, and eukaryotes. Herein, we explored the whole genome of N. gonorrhoeae to mine evolutionary conserved GQ motifs. The Ng-GQs were highly enriched in the genes involved in various important biological and molecular processes of N. gonorrhoeae. Five of these GQ motifs were characterized using biophysical and biomolecular techniques. The GQ-specific ligand, BRACO-19, showed a high affinity towards these GQ motifs and stabilized them in both in vitro and in vivo conditions. The ligand showed potent anti-gonococcal activity and modulated the gene expression of the GQ-harboring genes. Strikingly, BRACO-19 also altered the biofilm formation in N. gonorrhoeae and its adhesion and invasion of the human cervical epithelial cells. In summary, the present study showed a significant role of GQ motifs in N. gonorrhoeae biology and put forward a step closer towards the search for therapeutic measures in combating the emerging antimicrobial resistance in the pathogen.

Key points

•Neisseria gonorrhoeae genome is enriched in non-canonical nucleic acid structures—G-quadruplexes.

•These G-quadruplexes might regulate bacterial growth, virulence, and pathogenesis.

•G-quadruplex ligands inhibit biofilm formation, adhesion, and invasion of the gonococcus bacterium.

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Data availability

All data generated or analyzed during this study are included in this published article (and its supplementary information files).

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Acknowledgements

Authors here acknowledge the Sophisticated Instrumentation (SIC) Facility at the Indian Institute of Technology Indore for CD, Confocal and fluorescence microscopy experiments. The authors gratefully acknowledge the DST-FIST NMR facility at the Department of Chemistry, Indian Institute of Technology Indore, for recording the NMR spectra. The mTFP-pET43a+ plasmid was a kind gift from Dr. Prashant Kodgire, IIT Indore. NJ thanks the Council of Scientific and Industrial Research (CSIR), New Delhi, India; US to the Ministry of Human Resource and Development (MHRD), New Delhi, India, and AS is thankful to the Department of Biotechnology, New Delhi, India, for their respective JRF/SRF fellowships.

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Authors and Affiliations

  1. Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore-IIT Indore, Khandwa Road, Simrol, Indore, Madhya Pradesh, 453 552, India

    Neha Jain, Uma Shankar, Aakriti Singh & Amit Kumar

  2. Gujarat Biotechnology University, Gandhinagar, 382355, India

    Tarun Kumar Sharma

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  1. Neha Jain
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  2. Uma Shankar
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  3. Aakriti Singh
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  4. Tarun Kumar Sharma
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  5. Amit Kumar
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Contributions

AK conceived and designed the experiments. NJ and US performed the experiments. AS performed NMR broadening. NJ, US, and AK analyzed the data and wrote the manuscript. TKS and AK proofread the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Amit Kumar.

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Jain, N., Shankar, U., Singh, A. et al. G-quadruplex motifs in Neisseria gonorrhoeae as anti-gonococcal targets. Appl Microbiol Biotechnol 107, 5145–5159 (2023). https://doi.org/10.1007/s00253-023-12646-6

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  • DOI: https://doi.org/10.1007/s00253-023-12646-6

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