Skip to main content
SpringerLink
Log in

Antimicrobial Mechanisms of Enterocin CHQS Against Candida albicans

  • Published:
Current Microbiology Aims and scope Submit manuscript

Abstract

Candida albicans is the most common fungal pathogen in hospital-acquired infections, which is extremely harmful to health. The increasing fungal infections is requiring the rapid development of novel antifungal agents. In this study, the antimicrobial activity of CHQS, an enterocin isolated from Enterococcus faecalis TG2 against C. albicans was confirmed by the minimum inhibitory concentration, minimum fungicidal concentration, and time–kill curve. Aniline blue and calcofluor white staining methods showed that CHQS remarkably affected β-1,3-glucan and chitin cell wall components and made cell wall more vulnerable. The C. albicans cell wall rupture and intracellular vacuolation were observed by TEM and SEM. Moreover, CHQS induced the accumulation of intracellular reactive oxygen species and decreased mitochondrial membrane potential. These results suggested that CHQS might have a complex multi-target antimicrobial mechanism against C. albicans. In addition, the use of CHQS combined with amphotericin B showed synergistic antimicrobial effects against C. albicans. In conclusion, enterocin CHQS, a natural product with antimicrobial effect, might has a bright future for the development of new antifungal drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

All data generated or analyzed during this study are included in this published article.

Code Availability

Not applicable.

Abbreviations

PI:

Propidium iodide

AmB:

Amphotericin B

MIC:

Minimum inhibitory concentration

MFC:

Minimum fungicidal concentration

CLSI:

Clinical and laboratory standards institute

FICI:

Fraction inhibitory concentration index

CSH:

Cell surface hydrophobicity

ROS:

Reactive oxygen species

Δψm:

Mitochondrial membrane potential

CFW:

Calcofluor white

Rh123:

Rhodamine 123

References

  1. Costa-de-Oliveira S, Rodrigues AG (2020) Candida albicans antifungal resistance and tolerance in bloodstream infections: the triad yeast-host-antifungal. Microorganisms 8(2):154. https://doi.org/10.3390/microorganisms8020154

    Article  CAS  PubMed Central  Google Scholar 

  2. Bertolini M, Dongari-Bagtzoglou A (2019) The relationship of Candida albicans with the oral bacterial microbiome in health and disease. Springer International Publishing, Cham, pp 69–78

    Google Scholar 

  3. Swidergall M (2019) Candida albicans at host barrier sites: pattern recognition receptors and beyond. Pathogens 8(1):40. https://doi.org/10.3390/pathogens8010040

    Article  CAS  PubMed Central  Google Scholar 

  4. Lee Y, Puumala E, Robbins N, Cowen LE (2021) Antifungal drug resistance: molecular mechanisms in Candida albicans and beyond. Chem Rev 121(6):3390–3411. https://doi.org/10.1021/acs.chemrev.0c00199

    Article  CAS  PubMed  Google Scholar 

  5. Galgóczy L, Marx F (2019) Do antimicrobial proteins contribute to overcoming the hidden antifungal crisis at the dawn of a post-antibiotic era? Microorganisms 7(1):16. https://doi.org/10.3390/microorganisms7010016

    Article  CAS  PubMed Central  Google Scholar 

  6. Roshan N, Riley TV, Knight DR, Steer JH, Hammer KA (2019) Natural products show diverse mechanisms of action against Clostridium difficile. J Appl Microbiol 126(2):468–479. https://doi.org/10.1111/jam.14152

    Article  CAS  PubMed  Google Scholar 

  7. Heard SC, Wu G, Winter JM (2021) Antifungal natural products. Curr Opin Biotechnol 69:232–241. https://doi.org/10.1016/j.copbio.2021.02.001

    Article  CAS  PubMed  Google Scholar 

  8. Lohans CT, Vederas JC (2012) Development of class IIa bacteriocins as therapeutic agents. Int J Microbiol 2012:386410. https://doi.org/10.1155/2012/386410

    Article  CAS  PubMed  Google Scholar 

  9. Wang Y, Qin Y, Zhang Y, Wu R, Li P (2019) Antibacterial mechanism of plantaricin LPL-1, a novel class IIa bacteriocin against Listeria monocytogenes. Food Control 97:87–93. https://doi.org/10.1016/j.foodcont.2018.10.025

    Article  CAS  Google Scholar 

  10. Xi Q, Wang J, Du R, Zhao F, Han Y, Zhou Z (2018) Purification and characterization of bacteriocin produced by a strain of Enterococcus faecalis TG2. Appl Biochem Biotechnol 184(4):1106–1119. https://doi.org/10.1007/s12010-017-2614-1

    Article  CAS  PubMed  Google Scholar 

  11. Buda De Cesare G, Cristy SA, Garsin DA, Lorenz MC (2020) Antimicrobial peptides: a new frontier in antifungal therapy. MBio 11(6):e02123-e12120. https://doi.org/10.1128/mBio.02123-20

    Article  PubMed  PubMed Central  Google Scholar 

  12. Jafri H, Ahmad I (2020) Thymus vulgaris essential oil and thymol inhibit biofilms and interact synergistically with antifungal drugs against drug resistant strains of Candida albicans and Candida tropicalis. J Mycologie Médicale 30(1):100911. https://doi.org/10.1016/j.mycmed.2019.100911

    Article  CAS  Google Scholar 

  13. Corona A, Vercelli A, Bruni N, Guidi E, Cornegliani L (2021) In vitro activity of lactoferricin solution against Malassezia pachydermatis from otitis externa in dogs and cats. Vet Dermatol 32(4):316-e386. https://doi.org/10.1111/vde.12973

    Article  PubMed  Google Scholar 

  14. Roshanak S, Shahidi F, Tabatabaei Yazdi F, Javadmanesh A, Movaffagh J (2020) Evaluation of antimicrobial activity of buforin I and nisin and synergistic effect of the combination of them as a novel antimicrobial preservative. J Food Prot. https://doi.org/10.4315/JFP-20-127

    Article  PubMed  Google Scholar 

  15. Odds FC (2003) Synergy, antagonism, and what the chequerboard puts between them. J Antimicrob Chemother 52(1):1. https://doi.org/10.1093/jac/dkg301

    Article  PubMed  Google Scholar 

  16. Liu G, Ren G, Zhao L, Cheng L, Wang C, Sun B (2017) Antibacterial activity and mechanism of bifidocin A against Listeria monocytogenes. Food Control 73:854–861. https://doi.org/10.1016/j.foodcont.2016.09.036

    Article  CAS  Google Scholar 

  17. Reddy GKK, Nancharaiah YV (2020) Alkylimidazolium ionic liquids as antifungal alternatives: antibiofilm activity against Candida albicans and underlying mechanism of action. Front Microbiol 11:730–730. https://doi.org/10.3389/fmicb.2020.00730

    Article  PubMed  PubMed Central  Google Scholar 

  18. Nataraj BH, Ramesh C, Mallappa RH (2021) Characterization of antibiotic resistance and virulence traits present in clinical methicillin-resistant Staphylococcus aureus Isolates. Curr Microbiol 78(5):2001–2014. https://doi.org/10.1007/s00284-021-02477-x

    Article  CAS  PubMed  Google Scholar 

  19. Liu Y, Lu J, Sun J, Zhu X, Zhou L, Lu Z, Lu Y (2019) C16-fengycin A affect the growth of Candida albicans by destroying its cell wall and accumulating reactive oxygen species. Appl Microbiol Biotechnol 103(21–22):8963–8975. https://doi.org/10.1007/s00253-019-10117-5

    Article  CAS  PubMed  Google Scholar 

  20. Lee HS, Kim Y (2020) Aucklandia lappa causes cell wall damage in Candida albicans by reducing chitin and (1, 3)-β-D-glucan. J Microbiol Biotechnol 30(7):967–973. https://doi.org/10.4014/jmb.2002.02025

    Article  CAS  PubMed  Google Scholar 

  21. Lee HS, Kim Y (2017) Paeonia lactiflora inhibits cell wall synthesis and triggers membrane depolarization in Candida albicans. J Microbiol Biotechnol 27(2):395–404. https://doi.org/10.4014/jmb.1611.11064

    Article  CAS  PubMed  Google Scholar 

  22. Tan Z, Bo T, Guo F, Cui J, Jia S (2018) Effects of epsilon-poly-l-lysine on the cell wall of Saccharomyces cerevisiae and its involved antimicrobial mechanism. Int J Biol Macromol 118(Pt B):2230–2236. https://doi.org/10.1016/j.ijbiomac.2018.07.094

    Article  CAS  PubMed  Google Scholar 

  23. Li Y, Shan M, Zhu Y, Yao H, Li H, Gu B, Zhu Z (2020) Kalopanaxsaponin A induces reactive oxygen species mediated mitochondrial dysfunction and cell membrane destruction in Candida albicans. PLoS ONE 15(11):e0243066. https://doi.org/10.1371/journal.pone.0243066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Moore J, Rajasekaran K, Cary JW, Chlan C (2018) Mode of action of the antimicrobial peptide D4E1 on Aspergillus flavus. Int J Pept Res Ther 25(3):1135–1145. https://doi.org/10.1007/s10989-018-9762-1

    Article  CAS  Google Scholar 

  25. Gong Y, Liu W, Huang X, Hao L, Li Y, Sun S (2019) Antifungal activity and potential mechanism of N-butylphthalide alone and in combination with fluconazole against Candida albicans. Front Microbiol 10:1461. https://doi.org/10.3389/fmicb.2019.01461

    Article  PubMed  PubMed Central  Google Scholar 

  26. Luo Y, McLean DTF, Linden GJ, McAuley DF, McMullan R, Lundy FT (2017) The naturally occurring host defense peptide, LL-37, and its truncated mimetics KE-18 and KR-12 have selected biocidal and antibiofilm activities against Candida albicans, Staphylococcus aureus, and Escherichia coli in vitro. Front Microbiol. https://doi.org/10.3389/fmicb.2017.00544

    Article  PubMed  PubMed Central  Google Scholar 

  27. Li R, Tao M, Li S, Wang X, Yang Y, Mo L, Zhang K, Wei A, Huang L (2021) Internalization and membrane activity of the antimicrobial peptide CGA-N12. Biochem J 478:1907–1919. https://doi.org/10.1042/BCJ20201006

    Article  CAS  PubMed  Google Scholar 

  28. Han Y, Chen P, Zhang Y, Lu W, Ding W, Luo Y, Wen S, Xu R, Liu P, Huang P (2019) Synergy between auranofin and celecoxib against colon cancer in vitro and in vivo through a novel redox-mediated mechanism. Cancers (Basel) 11(7):931. https://doi.org/10.3390/cancers11070931

    Article  CAS  Google Scholar 

  29. Liu J, Gefen O, Ronin I, Bar-Meir M, Balaban NQ (2020) Effect of tolerance on the evolution of antibiotic resistance under drug combinations. Science 367(6474):200–204. https://doi.org/10.1126/science.aay3041

    Article  CAS  PubMed  Google Scholar 

  30. O’Brien B, Chaturvedi S, Chaturvedi V (2020) In vitro evaluation of antifungal drug combinations against multidrug-resistant Candida auris isolates from New York outbreak. Antimicrob Agents Chemother 64(4):e02195-e12119. https://doi.org/10.1128/AAC.02195-19

    Article  PubMed  PubMed Central  Google Scholar 

  31. Gabriel I (2020) ‘Acridines’ as new horizons in antifungal treatment. Molecules 25(7):1480. https://doi.org/10.3390/molecules25071480

    Article  CAS  PubMed Central  Google Scholar 

  32. Seyedjavadi SS, Khani S, Eslamifar A, Ajdary S, Goudarzi M, Halabian R, Akbari R, Zare-Zardini H, Imani Fooladi AA, Amani J, Razzaghi-Abyaneh M (2020) The antifungal peptide MCh-AMP1 derived from Matricaria chamomilla inhibits Candida albicans growth via inducing ROS generation and altering fungal cell membrane permeability. Front Microbiol. https://doi.org/10.3389/fmicb.2019.03150

    Article  PubMed  PubMed Central  Google Scholar 

  33. Ma HZX, Yang L, Su P, Fu P, Peng J, Yang N, Guo G (2020) Antimicrobial peptide AMP-17 affects Candida albicans by disrupting its cell wall and cell membrane integrity. Infect Drug Resist 13:2509–2520. https://doi.org/10.2147/IDR.S250278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Reyna-Beltrán E, Isaac Bazán Méndez C, Iranzo M, Mormeneo S, Pedro Luna-Arias J (2019) The cell wall of Candida albicans: a proteomics view. Candida Albicans 12:71–92

    Google Scholar 

  35. Walker LA, Munro CA (2020) Caspofungin induced cell wall changes of Candida species influences macrophage interactions. Front Cell Infect Microbiol 10:164. https://doi.org/10.3389/fcimb.2020.00164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Nakamura H, Takada K (2021) Reactive oxygen species in cancer: current findings and future directions. Cancer Sci 112(10):3945–3952. https://doi.org/10.1111/cas.15068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kwun MS, Lee DG (2020) An insight on the role of nitric oxide in yeast apoptosis of curcumin-treated Candida albicans. Curr Microbiol 77(10):3104–3113. https://doi.org/10.1007/s00284-020-02132-x

    Article  CAS  PubMed  Google Scholar 

  38. Chen R-C, Lan C-Y (2020) Human antimicrobial peptide hepcidin 25-induced apoptosis in Candida albicans. Microorganisms 8(4):585. https://doi.org/10.3390/microorganisms8040585

    Article  CAS  PubMed Central  Google Scholar 

  39. De Zoysa GH, Glossop HD, Sarojini V (2018) Unexplored antifungal activity of linear battacin lipopeptides against planktonic and mature biofilms of C. albicans. Eur J Med Chem 146:344–353. https://doi.org/10.1016/j.ejmech.2018.01.023

    Article  CAS  PubMed  Google Scholar 

  40. Chang C-K, Kao M-C, Lan C-Y (2021) Antimicrobial activity of the peptide LfcinB15 against Candida albicans. J Fungi 7(7):519

    Article  CAS  Google Scholar 

  41. Yu Q, Zhang B, Li J, Zhang B, Wang H, Li M (2016) Endoplasmic reticulum-derived reactive oxygen species (ROS) is involved in toxicity of cell wall stress to Candida albicans. Free Radic Biol Med 99:572–583. https://doi.org/10.1016/j.freeradbiomed.2016.09.014

    Article  CAS  PubMed  Google Scholar 

  42. Liu X, Yang C, Deng Y, Liu P, Yang H, Du X, Du Y (2021) Polygoni multiflori radix preparat delays skin aging by inducing mitophagy. Biomed Res Int 2021:5847153–5847153. https://doi.org/10.1155/2021/5847153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the Key Technology Research and Development Plan of Tianjin Municipal Science and Technology Bureau, China (19YFZCSN00100).

Author information

Authors and Affiliations

  1. School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, China

    Qi Wang, Lei Pan, Ye Han & Zhijiang Zhou

Authors
  1. Qi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lei Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ye Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhijiang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

QW and ZJZ conceived and designed the research. QW and LP constructed the experiments and analyzed the data. QW, ZJZ, YH, and LP conducted the experiments.

Corresponding authors

Correspondence to Ye Han or Zhijiang Zhou.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics Approval

Not applicable.

Consent to Participate

Not applicable.

Consent for Publication

This manuscript is original and not published elsewhere. The authors discussed the results, read, and approved the final version of this manuscript. The authors also confirm that there are no ethical issues associated with the publication of this manuscript.

Informed Consent

Not applicable.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 61 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Q., Pan, L., Han, Y. et al. Antimicrobial Mechanisms of Enterocin CHQS Against Candida albicans. Curr Microbiol 79, 191 (2022). https://doi.org/10.1007/s00284-022-02878-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00284-022-02878-6

Search

Navigation