Skip to main content

Bacillomycin D effectively controls growth of Malassezia globosa by disrupting the cell membrane

Applied Microbiology and Biotechnology volume 104, pages 3529–3540 (2020)Cite this article

Abstract

Malassezia globosa is an opportunistic pathogen that causes various skin disorders, which disturbs people’s life all the time, and conventional drugs are not completely satisfactory. Bacillomycin D (BD), an antifungal lipopeptide, could inhibit various fungi growth. However, the reports about its effect on M. globosa were not found yet. In this study, we showed that BD and BD-C16 (fatty acid chain had sixteen carbon atoms) completely inhibited growth of M. globosa at concentration of 64 μg/ml in 15 h, which was confirmed with the observation of irregular morphological change of M. globosa treated with BD. Significantly, the study on the working mechanism showed that BD induced cell death by changing cell membrane permeability and thus promoting the release of cellular contents, which may be mediated by the interaction between BD and ergosterol from membrane. Further study showed that BD reduced the overall content of cellular sterol, and interestingly, the expression of some genes involved in membrane and ergosterol synthesis were significantly upregulated, which was likely to be a feedback regulation. Besides, we found that BD had additive and synergistic effects with ketoconazole and amphotericin B, respectively, on inhibition of M. globosa, suggesting that combination use of BD with other commercial drugs could be a promising strategy to relieve skin disorders caused by M. globosa.

Key Points

• BD could efficiently inhibit the growth of M. globosa.

• BD increases cell membrane permeability and thus promotes the release of cellular contents.

• BD has additive or synergistic effect with other antifungal drugs.

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

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

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

References

  • Anderson TM, Clay MC, Cioffi AG, Diaz KA, Hisao GS, Tuttle MD, Nieuwkoop AJ, Comellas G, Maryum N, Wang S, Uno BE, Wildeman EL, Gonen T, Rienstra CM, Burke MD (2014) Nature amphotericin forms an extramembranous and fungicidal sterol sponge. Nat Chem Biol 10(5):400–406

    CAS  PubMed  PubMed Central  Google Scholar 

  • Angiolella L, Carradori S, Maccallini C, Giusiano G, Supuran CT (2017) Targeting Malassezia species for novel synthetic and natural antidandruff agents. Curr Med Chem 24(22):2392–2412

    CAS  PubMed  Google Scholar 

  • Arthington-Skaggs BA, Jradi H, Desai T, Morrison CJ (1999) Quantitation of ergosterol content: novel method for determination of fluconazole susceptibility of Candida albicans. J Clin Microbiol 37(10):3332–3337

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bao VW, Leung KM, Kwok KW, Zhang AQ, Lui GC (2008) Synergistic toxic effects of zinc pyrithione and copper to three marine species: implications on setting appropriate water quality criteria. Mar Pollut Bull 57(6–12):616–623

    CAS  PubMed  Google Scholar 

  • Breivik O, Owades J (1957) Yeast analysis, spectrophotometric semimicrodetermination of ergosterol in yeast. J Agric Food Chem 5(5):360–363

    CAS  Google Scholar 

  • Caulier S, Nannan C, Gillis A, Licciardi F, Bragard C, Mahillon J (2019) Overview of the antimicrobial compounds produced by members of the Bacillus subtilis group. Front Microbiol 10:302

    PubMed  PubMed Central  Google Scholar 

  • Chai HB, Allen WE, Hicks RP (2014) Spectroscopic investigations of the binding mechanisms between antimicrobial peptides and membrane models of Pseudomonas aeruginosa and Klebsiella pneumoniae. Bioorg Med Chem 22(15):4210–4222

    CAS  PubMed  Google Scholar 

  • De Castro RD, De Souza TMPA, Bezerra LMD, Ferreira GLS, De Brito Costa EMM, Cavalcanti AL (2015) Antifungal activity and mode of action of thymol and its synergism with nystatin against Candida species involved with infections in the oral cavity: an in vitro study. BMC Complem Altern M 15(1):417

    Google Scholar 

  • Derry KM, Deborah AO (2013) Peptides as the next generation of anti-infectives. Future Med Chem 5(3):315–337

    Google Scholar 

  • Dolenc-Voljč M (2017) Diseases caused by Malassezia species in human beings the microbiology of skin, soft tissue, bone and joint infections. Elsevier, Amsterdam

    Google Scholar 

  • Erchiga VC, Florencio VD (2002) Malassezia species in skin diseases. Curr Opin Infect Dis 15(2):133–142

    Google Scholar 

  • Faergemann J (1979) Tinea versicolor and Pityrosporum orbiculare: mycological investigations, experimental infections and epidemiological surveys. Acta Derm Venereol Suppl 86:1–23

    Google Scholar 

  • Frost DJ, Brandt KD, Cugier D, Goldman R (1995) A whole-cell Candida albicans assay for the detection of inhibitors towards fungal cell wall synthesis and assembly. J Antibiot 48(4):306–310

    CAS  PubMed  Google Scholar 

  • Gaitanis G, Velegraki A, Mayser P, Bassukas ID (2013) Skin diseases associated with Malassezia yeasts: facts and controversies. Clin Dermatol 31(4):455–463

    PubMed  Google Scholar 

  • Ghajarzadeh M, Ghiasi M, Kheirkhah S (2012) Associations between skin diseases and quality of life: a comparison of psoriasis, vitiligo, and alopecia areata. Acta Medica Iranica 50(7):511–515

    PubMed  Google Scholar 

  • Goka K (1999) Embryotoxicity of zinc pyrithione, an antidandruff chemical, in fish. Environ Res 81(1):81–83

    CAS  PubMed  Google Scholar 

  • Gong QW, Zhang C, Lu FX, Zhao HZ, Bie XM, Lu ZX (2014) Identification of bacillomycin D from Bacillus subtilis fmbJ and its inhibition effects against Aspergillus flavus. Food Control 36(1):8–14

    CAS  Google Scholar 

  • Gu Q, Yang Y, Yuan Q, Shi G, Wu L, Lou Z, Huo R, Wu H, Borriss R, Gao X (2017) Bacillomycin D produced by Bacillus amyloliquefaciens is involved in the antagonistic interaction with the plant-pathogenic fungus Fusarium graminearum. Appl Environ Microbiol 83(19):1075–1077

    Google Scholar 

  • Güngör S, Erdal MS, Aksu B (2013) New formulation strategies in topical antifungal therapy. J DermatolL Sci 3(1):56–65

    Google Scholar 

  • Guo S, Huang W, Zhang J, Wang Y (2015) Novel inhibitor against Malassezia globosa LIP1 (SMG1), a potential anti-dandruff target. Bioorg Med Chem Lett 25(17):3464–3467

    CAS  PubMed  Google Scholar 

  • Gupta AK, Batra R, Bluhm R, Boekhout T, Dawson TL Jr (2004) Skin diseases associated with Malassezia species. J Am Acad Dermatol 51(5):785–798

    PubMed  Google Scholar 

  • Hajare SN, Subramanian M, Gautam S, Sharma A (2013) Induction of apoptosis in human cancer cells by a Bacillus lipopeptide bacillomycin D. Biochimie 95(9):1722–1731

    CAS  PubMed  Google Scholar 

  • Hay RJ, Johns NE, Williams HC, Bolliger LW, Dellavalle RP, Margolis DJ, Marks R, Naldi L, Weinstock MA, Wulf SK (2014) The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J Invest Dermatol 134(6):1527–1534

    CAS  PubMed  Google Scholar 

  • Jacques P (2011) Surfactin and other lipopeptides from Bacillus spp biosurfactants. Springer, Berlin

    Google Scholar 

  • Juntachai W, Oura T, Murayama SY, Kajiwara S (2009) The lipolytic enzymes activities of Malassezia species. Med Mycol 47(5):477–484

    CAS  PubMed  Google Scholar 

  • Kim P, Ryu J, Kim YH, Chi YT (2010) Production of biosurfactant lipopeptides iturin A, fengycin and surfactin A from Bacillus subtilis CMB32 for control of Colletotrichum gloeosporioides. J Microbiol Biotechnol 20(1):138–145

    CAS  PubMed  Google Scholar 

  • Klepser ME, Ernst EJ, Lewis RE, Ernst ME, Pfaller MA (1998) Influence of test conditions on antifungal time-kill curve results: proposal for standardized methods. Antimicrob Agents Ch 42(5):1207–1212

    CAS  Google Scholar 

  • Kocsis B, Kustos I, Kilár F, Nyul A, Jakus PB, Kerekes S, Villarreal V, Prókai L, Lóránd T (2009) Antifungal unsaturated cyclic Mannich ketones and amino alcohols: study of mechanism of action. Eur J Med Chem 44(5):1823–1829

    CAS  PubMed  Google Scholar 

  • Kontoyiannis DP, Lewis RE (2002) Antifungal drug resistance of pathogenic fungi. Lancet 359(9312):1135–1144

    CAS  PubMed  Google Scholar 

  • Koumoutsi A, Chen XH, Henne A, Liesegang H, Hitzeroth G, Franke P, Vater J, Borriss R (2004) Structural and functional characterization of gene clusters directing nonribosomal synthesis of bioactive cyclic lipopeptides in Bacillus amyloliquefaciens strain FZB42. J Bacteriol 186(4):1084–1096

    CAS  PubMed  PubMed Central  Google Scholar 

  • Landy M, Warren GH, RosenmanM SB, Colio LG (1948) Bacillomycin: an antibiotic from Bacillus subtilis active against pathogenic fungi. Exp Biol Med 67(4):539–541

    CAS  Google Scholar 

  • Lee H, Lee DG (2018) Novel approaches for efficient antifungal drug action. J Microbiol Biotechnol 28(11):1771–1781

    PubMed  Google Scholar 

  • Lee KH, Kim YG, Bang D, Kim YA (1989) Scanning electron microscopy of Malassezia furfur in tinea versicolor. Yonsei Med J 30(4):334–338

    CAS  PubMed  Google Scholar 

  • Leeming JP, Notman FH (1987) Improved methods for isolation and enumeration of Malassezia furfur from human skin. J Clin Microbiol 25(10):2017–2019

    CAS  PubMed  PubMed Central  Google Scholar 

  • Leite MCA, Bezerra APB, Sousa JP, Guerra FQS, Lima EO (2014) Evaluation of antifungal activity and mechanism of action of citral against Candida albicans. Evid-Based Compl Alt 2014:2014

    Google Scholar 

  • Maget-Dana R, Thimon L, Peypoux F, Ptak M (1992) Surfactin/iturin A interactions may explain the synergistic effect of surfactin on the biological properties of iturin A. Biochimie 74(12):1047–1051

    CAS  PubMed  Google Scholar 

  • Moyne AL, Shelby R, Cleveland TE, Tuzun S (2001) Bacillomycin D: an iturin with antifungal activity against Aspergillus flavus. J Appl Microbiol 90(4):622–629

    CAS  PubMed  Google Scholar 

  • Munoz-Garay C, Munusamy S, Bulbarela AL, Vazquez R, Herlax V, Mate S, Carreon LS (2018) Membrane binding properties of Bacillomycin-D derivatives with model membranes composed of different sterols. Biophys J 114(3):613

    Google Scholar 

  • Nasir MN, Besson F (2012) Conformational analyses of bacillomycin D, a natural antimicrobial lipopeptide, alone or in interaction with lipid monolayers at the air–water interface. J Colloid Interface Sci 387(1):187–193

    CAS  PubMed  Google Scholar 

  • Nish S, Medzhitov R (2011) Host defense pathways: role of redundancy and compensation in infectious disease phenotypes. Immunity 34(5):629–636

    CAS  PubMed  PubMed Central  Google Scholar 

  • Perez AP, Altube MJ, Schilrreff P, Apezteguia G, Celes FS, Zacchino S, De Oliveira CI, Romero EL, Morilla MJ (2016) Topical amphotericin B in ultradeformable liposomes: formulation, skin penetration study, antifungal and antileishmanial activity in vitro. Colloid Surface B 139:190–198

    CAS  Google Scholar 

  • Perlin DS, Rautemaa-Richardson R, Alastruey-Izquierdo A (2017) The global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect Dis 17(12):383–392

    Google Scholar 

  • Peypoux F, Besson F, Michel G, Delcambe L (1981) Structure of bacillomycin D, a new antibiotic of the iturin group. Eur J Biochem 118(2):323–327

    CAS  PubMed  Google Scholar 

  • Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT–PCR. Nucleic Acids Res 29(9):45

    Google Scholar 

  • Reeder NL, Xu J, Youngquist RS, Schwartz JR, Rust RC, Saunders CW (2011) The antifungal mechanism of action of zinc pyrithione. Brit J Dermatol 165:9–12

    CAS  Google Scholar 

  • Tabbene O, Kalai L, Ben SL, Karkouch L, Elkahoui S, Gharbi A, Cosette P, Mangoni M, Jouenne T, Limam F (2011) Anti-Candida effect of bacillomycin D-like lipopeptides from Bacillus subtilis B38. FEMS Microbiol Lett 316(2):108–114

    CAS  PubMed  Google Scholar 

  • Tabbene O, Gharbi D, Slimene IB, Elkahoui S, Alfeddy MN, Cosette P, Mangoni ML, Jouenne T, Limam F (2012) Antioxidative and DNA protective effects of bacillomycin D-like lipopeptides produced by b38 strain. Appl Biochem Biotechnol 168(8):2245–2256

    CAS  PubMed  Google Scholar 

  • Tanaka K, Amaki Y, Ishihara A, Nakajima H (2015) Synergistic effects of [Ile7] surfactin homologues with bacillomycin D in suppression of gray mold disease by Bacillus amyloliquefaciens biocontrol strain SD-32. J Agric Food Chem 63(22):5344–5353

    CAS  PubMed  Google Scholar 

  • Tieman DM, Taylor MG, Ciardi JA, Klee HJ (2000) The tomato ethylene receptors NR and LeETR4 are negative regulators of ethylene response and exhibit functional compensation within a multigene family. P Natl Acad Sci USA 97(10):5663–5668

    CAS  Google Scholar 

  • White RL, Burgess DS, Manduru M, Bosso JA (1996) Comparison of three different in vitro methods of detecting synergy: time-kill, checkerboard, and E test. Antimicrob Agents Ch 40(8):1914–1918

    CAS  Google Scholar 

  • Xu J, Saunders CW, Hu P, Grant RA, Boekhout T, Kuramae EE, Kronstad JW, DeAngelis YM, Reeder NL, Johnstone KR, Leland M, Fieno AM, Begley WM, Sun Y, Lacey MP, Chaudhary T, Keough T, Chu L, Sears R, Yuan B, Dawson TL (2007) Dandruff-associated Malassezia genomes reveal convergent and divergent virulence traits shared with plant and human fungal pathogens. P Natl Acad Sci USA 104(47):18730–18735

    CAS  Google Scholar 

  • Yang L, Harroun TA, Weiss TM, Ding L, Huang HW (2001) Barrel-stave model or toroidal model? a case study on melittin pores. Biophys J 81(3):1475–1485

    PubMed  PubMed Central  Google Scholar 

  • Zhao HB, Shao DY, Jiang CM, Shi JL, Li Q, Huang QS, Rajoka MSR, Yang H, Jin ML (2017) Biological activity of lipopeptides from Bacillus. Appl Microbiol Biotechnol 101(15):5951–5960

    CAS  PubMed  Google Scholar 

  • Zhao Y, Liu YY, Sun J, Sha HT, Yang Y, Ye Q, Yang Q, Huang BQ, Yu YD, Huang H (2018) Acute toxic responses of embryo-larval zebrafish to zinc pyrithione (ZPT) reveal embryological and developmental toxicity. Chemosphere 205:62–70

    CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the National Natural and Science Foundation of China (No. 31771948).

Author information

Affiliations

  1. College of Food Science and Technology, Nanjing Agricultural University, 1 Weigang, Nanjing, 210095, China

    Tao Wu, Meirong Chen, Libang Zhou, Fengxia Lu, Xiaomei Bie & Zhaoxin Lu

Authors
  1. Tao Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Meirong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Libang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fengxia Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaomei Bie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhaoxin Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TW performed the experiments, analyzed the data, and wrote the manuscript. MC and LZ analyzed the data, and wrote the manuscript. FL and XB analyzed and discussed the data. ZL designed the research content, analyzed the data, and modified the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zhaoxin Lu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Publisher’s note

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wu, T., Chen, M., Zhou, L. et al. Bacillomycin D effectively controls growth of Malassezia globosa by disrupting the cell membrane. Appl Microbiol Biotechnol 104, 3529–3540 (2020). https://doi.org/10.1007/s00253-020-10462-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-020-10462-w

Keywords

  • Bacillomycin D
  • Malassezia globosa
  • Ergosterol
  • Synergistic effect