Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

KRN7000 analogues as biofilm disrupting agents against Streptococcus pyogenes and Proteus mirabilis

Abstract

In this study, three KRN7000 analogues with variations in the sugar and glycosidic linkage were synthesised to assess their efficacy in disrupting the biofilms of S. pyogenes and P. mirabilis. All three analogues exhibited antibacterial activity, with the effects being more prominent at lower concentrations in S. pyogenes. The N-alkylated, 1-deoxy analogue emerged as the most effective, significantly reducing biofilm formation and extracellular polymeric substances (EPS) in both organisms. Microscopic analysis revealed notable disruption of biofilm structure by the analogue, resulting in a significant reduction in EPS for both organisms and decreasing cell surface hydrophobicity. These results position the KRN7000 analogue as a promising candidate for developing glycolipid-based antibiofilm agents.

This is a preview of subscription content, access via your institution

Access options

Buy this article

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Inès M, Dhouha G. Glycolipid biosurfactants: Potential related biomedical and biotechnological applications. Carbohydr Res. 2015;416:59–69.

    Article  PubMed  Google Scholar 

  2. Shu Q, Lou H, Wei T, Liu X, Chen Q. Contributions of glycolipid biosurfactants and glycolipid-modified materials to antimicrobial strategy: a review. Pharmaceutics. 2021;13:227.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Firdose A, Maeda T, Sukri MAM, Yasin NHM, Sabturani N, Aqma WS. Antibacterial mechanism of Pseudomonas aeruginosa UKMP14T rhamnolipids against multidrug resistant Acinetobacter baumannii. Microb Pathog. 2024;193:106743.

    Article  PubMed  CAS  Google Scholar 

  4. Ceresa C, Hutton S, Lajarin-Cuesta M, Heaton R, Hargreaves I, Fracchia L, et al. Production of Mannosylerythritol Lipids (MELs) to be Used as Antimicrobial Agents Against S. aureus ATCC 6538. Curr Microbiol. 2020;77:1373–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Díaz De Rienzo MA, Banat IM, Dolman B, Winterburn J, Martin PJ. Sophorolipid biosurfactants: Possible uses as antibacterial and antibiofilm agent. N Biotechnol. 2015;32:720–6.

    Article  PubMed  Google Scholar 

  6. Boxley CJ, Hogan DE, Stolley RM, Maier RM. Synthetic approaches to production of rhamnolipid and related glycolipids. In: Biosurfactants. Elsevier, 2023, pp 251–63.

  7. Mukherji R, Prabhune A. Novel glycolipids synthesized using plant essential oils and their application in quorum sensing inhibition and as antibiofilm agents. Sci World J. 2014;2014:1–7.

    Article  Google Scholar 

  8. Maiti K, Syal K, Chatterji D, Jayaraman N. Synthetic arabinomannan heptasaccharide glycolipids inhibit biofilm growth and augment isoniazid effects in Mycobacterium smegmatis. ChemBioChem. 2017;18:1959–70.

    Article  PubMed  CAS  Google Scholar 

  9. Naresh K, Bharati BK, Avaji PG, Jayaraman N, Chatterji D. Synthetic arabinomannan glycolipids and their effects on growth and motility of the Mycobacterium smegmatis. Org Biomol Chem. 2010;8:592–9.

    Article  PubMed  CAS  Google Scholar 

  10. Perona A, Hoyos P, Ticona LA, García-Oliva C, Merchán A, Hernáiz MJ. Enzymatic synthesis and biological evaluation of glycolipids as potential antibacterial, antibiofilm and antiquorum sensing agents. Catal Today. 2024;433:114623.

    Article  CAS  Google Scholar 

  11. Thangarasu AK, Sambyal S, Kumar HMS, Lankalapalli RS. Design, synthesis, and preliminary immunopotentiating activity of new analogues of nojirimycin. Carbohydr Res. 2022;511:108479.

    Article  PubMed  CAS  Google Scholar 

  12. Natori T, Koezuka Y, Higa T. Agelasphins, novel α-galactosylceramides from the marine sponge Agelas mauritianus. Tetrahedron Lett. 1993;34:5591–2.

    Article  CAS  Google Scholar 

  13. Banchet-Cadeddu A, Hénon E, Dauchez M, Renault J-H, Monneaux F, Haudrechy A. The stimulating adventure of KRN 7000. Org Biomol Chem. 2011;9:3080.

    Article  PubMed  CAS  Google Scholar 

  14. Vieira ER, da Xisto MIDS, Pele MA, Alviano DS, Alviano CS, Barreto-Bergter E, et al. Monohexosylceramides from rhizopus species isolated from Brazilian caatinga: chemical characterization and evaluation of their antibiofilm and antibacterial activities. Molecules. 2018;23:1331.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Haas R, Gutman J, Wardrip NC, Kawahara K, Uhl W, Herzberg M, et al. Glycosphingolipids enhance bacterial attachment and fouling of nanofiltration membranes. Environ Sci Technol Lett. 2015;2:43–47.

    Article  CAS  Google Scholar 

  16. De Gregorio E, Esposito A, Vollaro A, De Fenza M, D’Alonzo D, Migliaccio A, et al. N-Nonyloxypentyl-l-Deoxynojirimycin Inhibits growth, biofilm formation and virulence factors expression of Staphylococcus aureus. Antibiotics. 2020;9:362.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kozień Ł, Gallienne E, Martin O, Front S, Strus M, Heczko P. PDIA, an iminosugar compound with a wide biofilm inhibitory spectrum covering both gram-positive and gram-negative human bacterial pathogens. Microorganisms. 2022;10:1222.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Cukkemane N, Bikker FJ, Nazmi K, Brand HS, Sotres J, Lindh L, et al. Anti‐adherence and bactericidal activity of sphingolipids against Streptococcus mutans. Eur J Oral Sci. 2015;123:221–7.

    Article  PubMed  CAS  Google Scholar 

  19. Tan LKK, Eccersley LRJ, Sriskandan S. Current views of haemolytic streptococcal pathogenesis. Curr Opin Infect Dis. 2014;27:155–64.

    Article  PubMed  Google Scholar 

  20. Walker MJ, Barnett TC, McArthur JD, Cole JN, Gillen CM, Henningham A, et al. Disease manifestations and pathogenic mechanisms of Group A streptococcus. Clin Microbiol Rev. 2014;27:264–301.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Schaffer JN, Pearson MM. Proteus mirabilis and Urinary Tract Infections. Microbiol Spectr 2015; 3. https://doi.org/10.1128/microbiolspec.UTI-0017-2013.

  22. Armbruster CE, Mobley HLT, Pearson MM. Pathogenesis of proteus mirabilis infection. EcoSal Plus 2018; 8. https://doi.org/10.1128/ecosalplus.esp-0009-2017.

  23. Mobley HL, Warren JW. Urease-positive bacteriuria and obstruction of long-term urinary catheters. J Clin Microbiol. 1987;25:2216–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Nucleo E, Fugazza G, Migliavacca R, Spalla M, Comelli M, Pagani L, et al. Differences in biofilm formation and aggregative adherence between β-lactam susceptible and β-lactamases producing P. mirabilis clinical isolates. New Microbiol. 2010;33:37–45.

    PubMed  Google Scholar 

  25. Wasfi R, Hamed SM, Amer MA, Fahmy LI. Proteus mirabilis Biofilm: Development and Therapeutic Strategies. Front Cell Infect Microbiol 2020; 10. https://doi.org/10.3389/fcimb.2020.00414.

  26. Pala M, Castelein MG, Dewaele C, Roelants SLKW, Soetaert WK, Stevens CV. Tuning the antimicrobial activity of microbial glycolipid biosurfactants through chemical modification. Front Bioeng Biotechnol 2024; 12. https://doi.org/10.3389/fbioe.2024.1347185.

  27. Jiang Y, Geng M, Bai L. Targeting biofilms therapy: current research strategies and development hurdles. Microorganisms. 2020;8:1222.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Rabin N, Zheng Y, Opoku-Temeng C, Du Y, Bonsu E, Sintim HO. Agents that inhibit bacterial biofilm formation. Future Med Chem. 2015;7:647–71.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Financial support from ICMR, India (Grant number: VIR/17/2020/ECD-I) is gratefully acknowledged.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Shiburaj Sugathan or Ravi S. Lankalapalli.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Krishnakumar, K.A., Remya Babu, R., Sugathan, S. et al. KRN7000 analogues as biofilm disrupting agents against Streptococcus pyogenes and Proteus mirabilis. J Antibiot 78, 246–255 (2025). https://doi.org/10.1038/s41429-025-00810-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41429-025-00810-1

Search

Quick links