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:

In vitro activity of ceragenins against Burkholderia cepacia complex

The Journal of Antibiotics volume 75, pages 403–409 (2022)Cite this article

Subjects

Abstract

Burkholderia cepacia complex (Bcc) species are aerobic, Gram-negative and non-fermantative bacilli. Bcc can cause clinical symptoms in patients with cystic fibrosis, ranging from asymptomatic carriage to fatal pneumonia. A pressing need exists for new antimicrobial agents that target Bcc. Ceragenins, CSA-13, CSA-131 and CSA-131 with 5% Pluronic® F127 (CSA-131P), were evaluated against Bcc clinical isolates (n = 42). MICs of ceragenins and conventional antibiotics were determined. Time-kill curve experiments were performed with 1x, 4x MICs of ceragenins and sulfamethoxazole-trimethoprim (SXT), levofloxacin. MIC50/ MIC90 results (mg l−1) of CSA-13, CSA-131 and CSA-131P were determined as 16/64, 16/128 and 16/128, respectively. CSA-13 and CSA-131 showed bactericidal activity. CSA-13 - levofloxacin combination displayed synergistic activity against Bcc. First-generation (CSA-13) and second-generation (CSA-131 and CSA-131P) ceragenins have significant antimicrobial effects on Bcc. The findings of this study demonstrate that combinations of ceragenins with currently marketed antibiotics could be synergistic in vitro against Bcc isolates. These results suggest that combination therapy with conventional antibiotics could be an alternative approach for treating Bcc infections in the future.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Akisoglu O, Engin D, Saricam S, Mustak H, Sener B, Hascelik G. Multilocus sequence analysis, biofilm production, antibiotic susceptibility and synergy tests of Burkholderia species in patients with and without cystic fibrosis. Mikrobiyol Bul. 2019;53:22–36.

    Article  Google Scholar 

  2. Burkholder WH. Sour skin, a bacterial rot of onion bulbs. Phytopathology. 1950;40:115–7.

    Google Scholar 

  3. Yabuuchi E, Kosako Y, Oyaizu H, Yano I, Hotta H, Hashimoto Y, et al. Proposal of Burkholderia gen. nov. and transfer of seven species of the genus Pseudomonas homology group II to the new genus, with the type species Burkholderia cepacia (Pallerioni and Holmes 1981) comb. nov. Microbiol Immunol. 1992;36:1251–75.

    Article  CAS  Google Scholar 

  4. Rhodes KA, Schweizer HP. Antibiotic Resistance in Burkholderia Species. Drug Resist Updat. 2016;28:82–90.

    Article  Google Scholar 

  5. Weinstein MP, et al. Performance standards for antimicrobial susceptibility testing. 28th ed. Wayne, PA: Clinical and Laboratory Standards Institute;; 2018. CLSI Supplement M100

    Google Scholar 

  6. Lai XZ, Feng Y, Pollard J, Chin JN, Rybak MJ, Bucki R, et al. Ceragenins: cholic acid- based mimics of antimicrobial peptids. Acc Chem Res. 2008;41:1233–40.

    Article  CAS  Google Scholar 

  7. Vaara M. Agents that increase the permeability of the outer membrane. Microbiol Rev. 1992;56:395–411.

    Article  CAS  Google Scholar 

  8. Li C, Budge LP, Driscoll CD, Willardson BM, Allman GW, Savage PB. Incremental conversion of outer membrane permeabilizers into potent antibiotics for Gram-negative bacteria. J Am Chem Soc. 1999;121:931–40.

    Article  CAS  Google Scholar 

  9. Schmidt EJ, Boswell JS, Walsh JP, Schellenberg MM, Winter TW, Li C, et al. Activities of cholic acid-derived antimicrobial agents against multidrug-resistant bacteria. J Antimicrobial Chem. 2001;47:671–4.

    Article  CAS  Google Scholar 

  10. Hashemi MM, Holden BS, Taylor MF, Wilson J, Coburn J, Hilton B, et al. Antibacterial and antifungal activities of poloxamer micelles containing ceragenin CSA-131 on ciliated tissues. Molecules. 2018;23:596.

    Article  Google Scholar 

  11. Regan KH, Bhatt J. Eradication therapy for Burkholderia cepacia complex in people with cystic fibrosis. Cochrane Database of Syst Rev. 2019;4:CS009876.

    Google Scholar 

  12. Barry AL, et al. Methods for determining a bactericidal activity of antimicrobial agents. 19th ed. Wayne, PA: Clinical and Laboratory Standards Institute;; 1999. Approved Guideline M26-A NCCLS

    Google Scholar 

  13. Soussa SA, Ramos CG, Leitao JH Burkholderia cepacia Complex: Emerging Multihost pathogens Equipped with a Wide Range of Virulence Factors and Determinants. Int J Microbiol 2011; pii: 607575.

  14. Kenna DTD, Lilley D, Coward A, Martin K, Perry C, Pike R, et al. Prevalence of Burkholderia species, including members of Burkholderia cepacia complex, among UK cystic and non-cystic fibrosis patients. J Med Microbiol. 2017;66:490–501.

    Article  Google Scholar 

  15. Bozkurt- Guzel C, Inci G, Oyardi O, Savage PB. Synergistic acitivity of ceragenins against Carbapenem- Resistant Acinetobacter baumannii isolates in both checkerboard and dynamic Time-Kill assays. Curr Microbiol. 2020;77:1419–28.

    Article  CAS  Google Scholar 

  16. Oyardi O, Savage PB, Erturan Z, Bozkurt-Guzel C. In vitro assessment of CSA-131 and CSA-131 poloxamer form for the treatment of Stenotrophomonas maltophilia infections in cystic fibrosis. J Antimicrob Chemother. 2021;76:443–50.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the Research Fund of Istanbul University. Project No: 34992.

Author information

Authors and Affiliations

  1. Istanbul University, Institute of Graduate Studies in Health Sciences, 34116, Istanbul, Turkey

    Elif Sena Demir

  2. Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, 34116, Istanbul, Turkey

    Elif Sena Demir, Ozlem Oyardi & Cagla Bozkurt-Guzel

  3. Department of Chemistry and Biochemistry, Brigham Young University, 84602, Provo, UT, USA

    Paul B. Savage

  4. Science for Life Laboratory, KTH – Royal Institute of Technology, Stockholm, 17121, Sweden

    Havva Ozlem Altay

Authors
  1. Elif Sena Demir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ozlem Oyardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul B. Savage
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Havva Ozlem Altay
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cagla Bozkurt-Guzel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elif Sena Demir.

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

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Demir, E.S., Oyardi, O., Savage, P.B. et al. In vitro activity of ceragenins against Burkholderia cepacia complex. J Antibiot 75, 403–409 (2022). https://doi.org/10.1038/s41429-022-00530-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41429-022-00530-w

Search

Advanced search

Quick links