Skip to main content

Advertisement

SpringerLink
Log in

Scolopendin 2 leads to cellular stress response in Candida albicans

  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

Centipedes, a kind of arthropod, have been reported to produce antimicrobial peptides as part of an innate immune response. Scolopendin 2 (AGLQFPVGRIGRLLRK) is a novel antimicrobial peptide derived from the body of the centipede Scolopendra subspinipes mutilans by using RNA sequencing. To investigate the intracellular responses induced by scolopendin 2, reactive oxygen species (ROS) and glutathione accumulation and lipid peroxidation were monitored over sublethal and lethal doses. Intracellular ROS and antioxidant molecule levels were elevated and lipids were peroxidized at sublethal concentrations. Moreover, the Ca2+ released from the endoplasmic reticulum accumulated in the cytosol and mitochondria. These stress responses were considered to be associated with yeast apoptosis. Candida albicans cells exposed to scolopendin 2 were identified using diagnostic markers of apoptotic response. Various responses such as phosphatidylserine externalization, chromatin condensation, and nuclear fragmentation were exhibited. Scolopendin 2 disrupted the mitochondrial membrane potential and activated metacaspase, which was mediated by cytochrome c release. In conclusion, treatment of C. albicans with scolopendin 2 induced the apoptotic response at sublethal doses, which in turn led to mitochondrial dysfunction, metacaspase activation, and cell death. The cationic antimicrobial peptide scolopendin 2 from the centipede is a potential antifungal peptide, triggering the apoptotic response.

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

Abbreviations

AMP:

Antimicrobial peptide

YPD:

Yeast extract-peptone dextrose

ROS:

Reactive oxygen species

H2-DCFDA:

2′,7′-Dichlorodihydrofluorescein diacetate

MDA:

Malondialdehyde

TCA:

Trichloroacetic acid

TBA:

Thiobarbituric acid

SSA:

5-Sulfosalicylic acid

GSSG:

Oxidized glutathione

GSH:

Reduced glutathione

PS:

Phosphatidylserine

DAPI:

4′-6-Diamidino-2-phenylindole

JC-1:

5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide

References

  1. Khan A, Ahmad A, Khan LA, Manzoor N (2014) Ocimum sanctum (L.) essential oil and its lead molecules induce apoptosis in Candida albicans. Res Microbiol 165:411–419

    Article  CAS  PubMed  Google Scholar 

  2. Davies J, Davies D (2010) Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev 74:417–433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wright GD (2005) Bacterial resistance to antibiotics: enzymatic degradation and modification. Adv Drug Deliv Rev 57:1451–1470

    Article  CAS  PubMed  Google Scholar 

  4. Nguyen LT, Haney EF, Vogel HJ (2011) The expanding scope of antimicrobial peptide structures and their mode of action. Trends Biotechnol 29:464–472

    Article  CAS  PubMed  Google Scholar 

  5. Franzenburg S, Walter J, Künzel S, Wang J, Baines JF, Bosch TC, Fraune S (2013) Distinct antimicrobial peptide expression determines host species-specific bacterial associations. Proc Natl Acad Sci USA 110:E3730–E3738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ogawa Y, Kawamura T, Matsuzawa T, Aoki R, Gee P, Yamashita A, Moriishi K, Yamasaki K, Koyanagi Y, Blauvelt A, Shimada S (2013) Antimicrobial peptide LL-37 produced by HSV-2-infected keratinocytes enhances HIV infection of Langerhans cells. Cell Host Microbe 13:77–86

    Article  CAS  PubMed  Google Scholar 

  7. Cado G, Aslam R, Séon L, Garnier T, Fabre R, Parat A, Chassepot A, Voegel JC, Senger B, Schneidr F, Frère Y, Jierry L, Schaaf P, Kerdjoudj H, Metz-boutigue MH, Boulmedais F (2013) Self-defensive biomaterial coating against bacteria and yeast: polysaccharide multilayer film with embedded antimicrobial peptide. Adv Funct Mater 23:4801–4809

    CAS  Google Scholar 

  8. Rong M, Yang S, Wen B, Mo G, Kang D, Liu J, Lin Z, Jiang W, Li B, Du C, Yang S, Jiang H, Feng Q, Xu X, Wang J, Lai R (2015) Peptidomics combined with cDNA library unravel the diversity of centipede venom. J Proteomics 114:28–37

    Article  CAS  PubMed  Google Scholar 

  9. Undheim EA, Fry BG, King GF (2015) Centipede venom: recent discoveries and current state of knowledge. Toxins 7:679–704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yang S, Xiao Y, Kang D, Liu J, Li U, Undheim EA, Klint JK, Rong M, Lai R, King GF (2013) Discovery of a selective NaV1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models. Proc Natl Acad Sci USA 110:17534–17539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Yoo WG, Lee JH, Shin Y, Shim JY, Jung M, Kang BC, Oh J, Seong J, Lee HK, Kong HS, Song KD, Yun EY, Kim IW, Kwon YN, Lee DG, Hwang UW, Park J, Hwang JS (2014) Antimicrobial peptides in the centipede Scolopendra subspinipes mutilans. Funct Integr Genomics 14:275–283

    Article  CAS  PubMed  Google Scholar 

  12. Lee H, Hwang JS, Lee J, Kim JI, Lee DG (2015) Scolopendin 2, a cationic antimicrobial peptide from centipede, and its membrane-active mechanism. Biochim Biophys Acta 1848:634–642

    Article  CAS  PubMed  Google Scholar 

  13. Choi H, Hwang JS, Lee DG (2014) Identification of a novel antimicrobial peptide, scolopendin 1, derived from centipede Scolopendra subspinipes mutilans and its antifungal mechanism. Insect Mol Biol 23:788–799

    Article  CAS  PubMed  Google Scholar 

  14. Wang P, Bang JK, Kim HJ, Kim JK, Shin Y (2009) Antimicrobial specificity and mechanism of action of disulfide-removed linear analogs of the plant-derived Cys-rich antimicrobial peptide Ib-AMP1. Peptides 30:2144–2149

    Article  CAS  PubMed  Google Scholar 

  15. Klepser M, Ernst EJ, Lewis RE, Ernst ME, Pfaller MA (1998) Influence of test conditions on antifungal time-kill curve results: proposal for standardized method. Antimicrob Agents Chemother 42:1207–1212

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Jakubowski W, Biliński T, Bartosz G (2000) Oxidative stress during aging of stationary cultures of the yeast Saccharomyces cerevisiae. Free Radic Biol Med 28:659–664

    Article  CAS  PubMed  Google Scholar 

  17. Park C, Lee DG (2010) Melittin induces apoptotic features in Candida albicans. Biochem Biophys Res Commun 394:170–172

    Article  CAS  PubMed  Google Scholar 

  18. Aubron C, Glodt J, Matar C, Huet O, Borderie D, Dobrindt U, Duranteau J, Denamur E, Conti M, Bouvet O (2012) Variation in endogenous oxidative stress in Escherichia coli natural isolates during growth in urine. BMC Microbiol 12:120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Slavi N, Rubinos C, Li L, Sellitto C, White TW, Mathias R, Srinivas M (2014) Connexin 46 (cx46) gap junctions provide a pathway for the delivery of glutathione to the lens nucleus. J Biol Chem 289:32694–32702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Arduino DM, Esteves AR, Domingues AF, Pereira CM, Cardoso SM, Oliveira CR (2009) ER-mediated stress induces mitochondrial-dependent caspases activation in NT2 neuron-like cells. BMB Rep 42:719–724

    Article  CAS  PubMed  Google Scholar 

  21. Madeo F, Herker E, Maldener C, Wissing S, Lachelt S, Herlan M, Fehr M, Lauber K, Sigrist SJ, Wesselborg S, Frolich KU (2002) A caspase-related protease regulates apoptosis in yeast. Mol Cell 9:911–917

    Article  CAS  PubMed  Google Scholar 

  22. Madeo F, Frohlich E, Fröhlich KU (1997) A yeast mutant showing diagnostic markers of early and late apoptosis. J Cell Biol 139:729–734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kapuscinski J (1995) DAPI: a DNA-specific fluorescent probe. Biotech Histochem 70:220–233

    Google Scholar 

  24. Almeida A, Almeida J, Bolanos JP, Moncada S (2001) Different responses of astrocytes and neurons to nitric oxide: the role of glycolytically generated ATP in astrocyte protection. Proc Natl Acad Sci USA 98:15294–15299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lowry OH, Rosebrough NJ, Farr AJ, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  26. Arnt L, Rennie JR, Linser S, Willumeit R, Tew GN (2006) Membrane activity of biomimetic facially amphiphilic antibiotics. J Phys Chem B 110:3527–3532

    Article  CAS  PubMed  Google Scholar 

  27. Vargas-Sánchez RD, Torrescano-Urrutia GR, Acedo-Félix E, Carvajal-Millán E, González-Córdova AF, Vallejo-Galland B, Torres-Llanez MJ, Sánchez-Escalante A (2014) Antioxidant and antimicrobial activity of commercial propolis extract in beef patties. J Food Sci 79:C1499–C1504

    Article  PubMed  Google Scholar 

  28. Munoz AJ, Wanichthanarak K, Meza E, Petranovic D (2012) Systems biology of yeast cell death. FEMS Yeast Res 12:249–265

    Article  CAS  PubMed  Google Scholar 

  29. Sandoval CM, Salzameda B, Reyes K, Williams T, Hohman VS, Plesniak LA (2007) Anti-obesity and anti-tumor pro-apoptotic peptides are sufficient to cause release of cytochrome c from vesicles. FEBS Lett 581:2463–5468

    Article  Google Scholar 

  30. Chudzik B, Koselski M, Czuryło A, Trębacz K, Gagoś M (2015) A new look at the antibiotic amphotericin B effect on Candida albicans plasma membrane permeability and cell viability functions. Eur Biophys J 44:77–90

    Article  CAS  PubMed  Google Scholar 

  31. Hao B, Cheng S, Clancy CJ, Nguyen MH (2013) Caspofungin kills Candida albicans by causing both cellular apoptosis and necrosis. Antimicrob Agents Chemother 57:326–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Silvestro L, Weiser JN, Axelsen PH (2000) Antibacterial and antimembrane activities of cecropin A in Escherichia coli. Antimicrobial Agents Chemother 44:602–607

    Article  CAS  Google Scholar 

  33. Andrä J, Berninghausen O, Leippe M (2001) Cecropins, antibacterial peptides from insects and mammals, are potently fungicidal against Candida albicans. Med Microbiol Immunol 189:169–173

    Article  PubMed  Google Scholar 

  34. Park CB, Yi KS, Matsuzaki K, Kim MS, Kim SC (2000) Structure-activity analysis of buforin II, a histone H2A-derived antimicrobial peptide: the proline hinge is responsible for the cell-penetrating ability of buforin II. Proc Natl Acad Sci USA 97:8245–8250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ruan Y, Shen T, Wang Y, Hou M, Li J, Sun T (2013) Antimicrobial peptide LL-37 attenuates LTA induced inflammatory effect in macrophages. Int Immunopharmacol 15:575–580

    Article  CAS  PubMed  Google Scholar 

  36. Wang C, Tian LL, Li S, Li HB, Zhou Y, Wang H, Yang QZ, Ma LJ, Shang DJ (2013) Rapid cytotoxicity of antimicrobial peptide tempoprin-1CEa in breast cancer cells through membrane destruction and intracellular calcium mechanism. PLoS One 8:e60462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Alvarez-Peral FJ, Zaragoza O, Pedreno Y, Argüelles JC (2002) Protective role of trehalose during severe oxidative stress caused by hydrogen peroxide and the adaptive oxidative stress response in Candida albicans. Microbiology 148:2599–2606

    Article  CAS  PubMed  Google Scholar 

  38. Singh V, Pal A, Darokar MP (2015) A polyphenolic flavonoid glabridin: oxidative stress response in multidrug-resistant Staphylococcus aureus. Free Radic Biol Med 87:48–57

    Article  CAS  PubMed  Google Scholar 

  39. Guo Z, Olsson L (2014) Physiological response of Saccharomyces cerevisiae to weak acids present in lignocellulosic hydrolysate. FEMS Yeast Res 14:1234–1248

    Article  CAS  PubMed  Google Scholar 

  40. Candiracci M, Citterio B, Piatti E (2012) Antifungal activity of the honey flavonoid extract against Candida albicans. Food Chem 131:493–499

    Article  CAS  Google Scholar 

  41. Perrone GG, Tan SX, Dawes IW (2008) Reactive oxygen species and yeast apoptosis. Biochim Biophys Acta 1783:1354–1368

    Article  CAS  PubMed  Google Scholar 

  42. Makovitzki A, Avrahami D, Shai Y (2006) Ultrashort antibacterial and antifungal lipopeptides. Proc Natl Acad Sci USA 103:15997–16002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Li H, Jiang W, Liu Y, Jiang J, Zhang Y, Wu P, Zhao J, Duan X, Zhou X, Feng L (2016) The metabolites of glutamine prevent hydroxyl radical-induced apoptosis through inhibiting calcium ion involved pathway in fish erythrocytes. Free Radic Biol Med 92:126–140

    Article  CAS  PubMed  Google Scholar 

  44. van den Eijnde SM, Boshart L, Baehrecke EH, De Zeeuw CI, Reutelingsperger CP, Vermeij-Keers C (1998) Cell surface exposure of phosphatidylserine during apoptosis is phylogenetically conserved. Apoptosis 3:9–16

    Article  PubMed  Google Scholar 

  45. Léger T, Garcia C, Ounissi M, Lelandais G, Camadro JM (2015) The metacaspase (Mca1p) has a dual role in farnesol-induced apoptosis in Candida albicans. Mol Cell Proteomics 14:93–108

    Article  PubMed  Google Scholar 

  46. Kyrylkova K, Kyryachenko S, Leid M, Kioussi C (2012) Detection of apoptosis by TUNEL assay. Methods Mol Biol 887:41–47

    Article  CAS  PubMed  Google Scholar 

  47. Reiter J, Herker E, Madeo F, Schmitt MJ (2015) Viral killer toxins induce caspase mediated apoptosis in yeast. J Cell Biol 168:353–358

    Article  Google Scholar 

  48. Pereira C, Camougrand N, Manon S, Sousa MJ, Côrte-Real M (2007) ADP/ATP carrier is required for mitochondrial outer membrane permeabilization and cytochrome c release in yeast apoptosis. Mol Microbiol 66:571–582

    Article  CAS  PubMed  Google Scholar 

  49. Shirtliff ME, Krom BP, Meijering RA, Peters BM, Zhu J, Scheper MA, Harris ML, Jabra-Rizk MA (2009) Farnesol-induced apoptosis in Candida albicans. Antimicrobial Agents Chemother 53:2392–2401

    Article  CAS  Google Scholar 

  50. Aerts AM, Carmona-Gutierrez D, Lefevre S, Govaert G, François IE, Madeo F, Santo RR, Cammue BP, Thevissen K (2009) The antifungal plant defensin RsAFP2 from radish induces apoptosis in a metacaspase independent way in Candida albicans. FEBS Lett 583:2513–2516

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the Next-Generation BioGreen 21 Program (Project No. PJ01104303), Rural Development Administration, Republic of Korea.

Author information

Author notes

    Authors and Affiliations

    1. BK 21 Plus KNU Creative BioResearch Group, School of Life Science, College of Natural Sciences, Kyungpook National University, 80 Daehakro, Bukgu, Daegu, 41566, Republic of Korea

      Heejeong Lee & Dong Gun Lee

    2. Department of Agricultural Biology, National Academy of Agricultural Science RDA, Jeonju, Republic of Korea

      Jae-Sam Hwang

    Authors
    1. Heejeong Lee
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Jae-Sam Hwang
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Dong Gun Lee
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Dong Gun Lee.

    Ethics declarations

    Conflict of interests

    The authors declare that they have no conflict of interest.

    Additional information

    Heejeong Lee and Jae-Sam Hwang have contributed equally to this work and should be considered co-first authors.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Lee, H., Hwang, JS. & Lee, D.G. Scolopendin 2 leads to cellular stress response in Candida albicans . Apoptosis 21, 856–865 (2016). https://doi.org/10.1007/s10495-016-1254-1

    Download citation

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10495-016-1254-1

    Keywords

    Search

    Navigation