Mycobiology

The Korean Society of Mycology (한국균학회)
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Antifungal Mechanism of Action of Lauryl Betaine Against Skin-Associated Fungus Malassezia restricta

  • Do, Eunsoo (Department of Systems Biotechnology, Chung-Ang University) ;
  • Lee, Hyun Gee (Safety Research Institute, Amorepacific R&D Center) ;
  • Park, Minji (Department of Systems Biotechnology, Chung-Ang University) ;
  • Cho, Yong-Joon (Korea Polar Research Institute) ;
  • Kim, Dong Hyeun (Department of Systems Biotechnology, Chung-Ang University) ;
  • Park, Se-Ho (Department of Systems Biotechnology, Chung-Ang University) ;
  • Eun, Daekyung (Safety Research Institute, Amorepacific R&D Center) ;
  • Park, Taehun (Safety Research Institute, Amorepacific R&D Center) ;
  • An, Susun (Safety Research Institute, Amorepacific R&D Center) ;
  • Jung, Won Hee (Department of Systems Biotechnology, Chung-Ang University)
  • Received : 2019.03.28
  • Accepted : 2019.05.24
  • Published : 2019.06.01
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Abstract

Betaine derivatives are considered major ingredients of shampoos and are commonly used as antistatic and viscosity-increasing agents. Several studies have also suggested that betaine derivatives can be used as antimicrobial agents. However, the antifungal activity and mechanism of action of betaine derivatives have not yet been fully understood. In this study, we investigated the antifungal activity of six betaine derivatives against Malassezia restricta, which is the most frequently isolated fungus from the human skin and is implicated in the development of dandruff. We found that, among the six betaine derivatives, lauryl betaine showed the most potent antifungal activity. The mechanism of action of lauryl betaine was studied mainly using another phylogenetically close model fungal organism, Cryptococcus neoformans, because of a lack of available genetic manipulation and functional genomics tools for M. restricta. Our genome-wide reverse genetic screening method using the C. neoformans gene deletion mutant library showed that the mutants with mutations in genes for cell membrane synthesis and integrity, particularly ergosterol synthesis, are highly sensitive to lauryl betaine. Furthermore, transcriptome changes in both C. neoformans and M. restricta cells grown in the presence of lauryl betaine were analyzed and the results indicated that the compound mainly affected cell membrane synthesis, particularly ergosterol synthesis. Overall, our data demonstrated that lauryl betaine influences ergosterol synthesis in C. neoformans and that the compound exerts a similar mechanism of action on M. restricta.

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References

  1. Craig SA. Betaine in human nutrition. Am J Clin Nutr. 2004;80:539-549. https://doi.org/10.1093/ajcn/80.3.539
  2. Kempson SA, Vovor-Dassu K, Day C. Betaine transport in kidney and liver: use of betaine in liver injury. Cell Physiol Biochem. 2013;32:32-40. https://doi.org/10.1159/000356622
  3. Teixido N, Canamas T, Usall J, et al. Accumulation of the compatible solutes, glycinebetaine and ectoine, in osmotic stress adaptation and heat shock cross-protection in the biocontrol agent Pantoea agglomerans CPA-2. Lett Appl Microbiol. 2005;41:248-252. https://doi.org/10.1111/j.1472-765X.2005.01757.x
  4. Burnett CL, Bergfeld WF, Belsito DV, et al. Safety assessment of alkyl betaines as used in cosmetics. Int J Toxicol. 2018;37:28S-46S. https://doi.org/10.1177/1091581818773354
  5. Birnie CR, Malamud D, Schnaare RL. Antimicrobial evaluation of N-alkyl betaines and N-alkyl-N, N-dimethylamine oxides with variations in chain length. Antimicrob Agents Chemother. 2000;44:2514-2517. https://doi.org/10.1128/AAC.44.9.2514-2517.2000
  6. Ahlstrom B, Thompson RA, Edebo L. The effect of hydrocarbon chain length, pH, and temperature on the binding and bactericidal effect of amphiphilic betaine esters on Salmonella typhimurium. APMIS. 1999;107:318-324. https://doi.org/10.1111/j.1699-0463.1999.tb01560.x
  7. Lindstedt M, Allenmark S, Thompson RA, et al. Antimicrobial activity of betaine esters, quaternary ammonium amphiphiles which spontaneously hydrolyze into nontoxic components. Antimicrob Agents Chemother. 1990;34:1949-1954. https://doi.org/10.1128/AAC.34.10.1949
  8. Diez-Pascual AM, Diez-Vicente AL. Poly(propylene fumarate)/polyethylene glycol-modified graphene oxide nanocomposites for tissue engineering. ACS Appl Mater Interfaces. 2016;8:17902-17914. https://doi.org/10.1021/acsami.6b05635
  9. Xu Z, Wang Z, Yuan C, et al. Dandruff is associated with the conjoined interactions between host and microorganisms. Sci Rep. 2016;6:srep24877.
  10. Findley K, Oh J, Yang J, et al. Topographic diversity of fungal and bacterial communities in human skin. Nature. 2013;498:367-370. https://doi.org/10.1038/nature12171
  11. Clavaud C, Jourdain R, Bar-Hen A, et al. Dandruff is associated with disequilibrium in the proportion of the major bacterial and fungal populations colonizing the scalp. PLoS One. 2013;8:e58203. https://doi.org/10.1371/journal.pone.0058203
  12. Takemoto A, Cho O, Morohoshi Y, et al. Molecular characterization of the skin fungal microbiome in patients with psoriasis. J Dermatol. 2015;42:166-170. https://doi.org/10.1111/1346-8138.12739
  13. Wang L, Clavaud C, Bar-Hen A, et al. Characterization of the major bacterial-fungal populations colonizing dandruff scalps in Shanghai, China, shows microbial disequilibrium. Exp Dermatol. 2015;24:398-400. https://doi.org/10.1111/exd.12684
  14. Park T, Kim HJ, Myeong NR, et al. Collapse of human scalp microbiome network in dandruff and seborrhoeic dermatitis. Exp Dermatol. 2017;26:835-838. https://doi.org/10.1111/exd.13293
  15. Park M, Cho YJ, Lee YW, et al. Whole genome sequencing analysis of the cutaneous pathogenic yeast Malassezia restricta and identification of the major lipase expressed on the scalp of patients with dandruff. Mycoses. 2017;60:188-197. https://doi.org/10.1111/myc.12586
  16. Perfect JR, Ketabchi N, Cox GM, et al. Karyotyping of Cryptococcus neoformans as an epidemiological tool. J Clin Microbiol. 1993;31: 3305-3309. https://doi.org/10.1128/JCM.31.12.3305-3309.1993
  17. Park M, Jung WH, Han SH, et al. Characterisation and expression analysis of MrLip1, a Class 3 Family Lipase of Malassezia restricta. Mycoses. 2015;58:671-678. https://doi.org/10.1111/myc.12412
  18. Toffaletti DL, Rude TH, Johnston SA, et al. Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA. J Bacteriol. 1993;175:1405-1411. https://doi.org/10.1128/jb.175.5.1405-1411.1993
  19. CLSI. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard. 3rd edition. CLSI document M27-A3. Wayne (PA): Clinical and Laboratory Standards Institute; 2008.
  20. Sugita T, Tajima M, Ito T, et al. Antifungal activities of tacrolimus and azole agents against the eleven currently accepted Malassezia species. J Clin Microbiol. 2005;43:2824-2829. https://doi.org/10.1128/JCM.43.6.2824-2829.2005
  21. Chun CD, Madhani HD. Applying genetics and molecular biology to the study of the human pathogen Cryptococcus neoformans. Methods Enzymol. 2010;470:797-831. https://doi.org/10.1016/S0076-6879(10)70033-1
  22. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2 DDCT method. Methods. 2001;25:402-408. https://doi.org/10.1006/meth.2001.1262
  23. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30:2114-2120. https://doi.org/10.1093/bioinformatics/btu170
  24. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012;9:357-359. https://doi.org/10.1038/nmeth.1923
  25. Liao Y, Smyth GK, Shi W. The subread aligner: fast, accurate and scalable read mapping by seedand-vote. Nucleic Acids Res. 2013;41:e108. https://doi.org/10.1093/nar/gkt214
  26. Wagner GP, Kin K, Lynch VJ. Measurement of mRNA abundance using RNA-seq data: RPKM measure is inconsistent among samples. Theory Biosci. 2012;131:281-285. https://doi.org/10.1007/s12064-012-0162-3
  27. Wei T, Geijer S, Lindberg M, et al. Detergents with different chemical properties induce variable degree of cytotoxicity and mRNA expression of lipid-metabolizing enzymes and differentiation markers in cultured keratinocytes. Toxicol in Vitro. 2006;20:1387-1394. https://doi.org/10.1016/j.tiv.2006.06.002
  28. Mowad CM. Contact allergens of the year. Adv Dermatol. 2004;20:237-255.
  29. Giaever G, Nislow C. The yeast deletion collection: a decade of functional genomics. Genetics. 2014;197:451-465. https://doi.org/10.1534/genetics.114.161620
  30. Motaung TE, Ells R, Pohl CH, et al. Genome-wide functional analysis in Candida albicans. Virulence. 2017;8:1563-1579. https://doi.org/10.1080/21505594.2017.1292198
  31. Xu D, Jiang B, Ketela T, et al. Genome-wide fitness test and mechanism-of-action studies of inhibitory compounds in Candida albicans. PLoS Pathog. 2007;3:e92. https://doi.org/10.1371/journal.ppat.0030092
  32. Saikia S, Oliveira D, Hu G, et al. Role of ferric reductases in iron acquisition and virulence in the fungal pathogen Cryptococcus neoformans. Infect Immun. 2014;82:839-850. https://doi.org/10.1128/IAI.01357-13
  33. Jung WH, Hu G, Kuo W, et al. Role of ferroxidases in iron uptake and virulence of Cryptococcus neoformans. Eukaryot Cell. 2009;8:1511-1520. https://doi.org/10.1128/EC.00166-09
  34. Jung WH, Sham A, Lian T, et al. Iron source preference and regulation of iron uptake in Cryptococcus neoformans. PLoS Pathog. 2008;4:e45. https://doi.org/10.1371/journal.ppat.0040045
  35. Sant DG, Tupe SG, Ramana CV, et al. Fungal cell membrane-promising drug target for antifungal therapy. J Appl Microbiol. 2016;21:1498-1510.
  36. Chang YC, Bien CM, Lee H, et al. Sre1p, a regulator of oxygen sensing and sterol homeostasis, is required for virulence in Cryptococcus neoformans. Mol Microbiol. 2007;64:614-629. https://doi.org/10.1111/j.1365-2958.2007.05676.x
  37. Chun CD, Liu OW, Madhani HD. A link between virulence and homeostatic responses to hypoxia during infection by the human fungal pathogen Cryptococcus neoformans. PLoS Pathog. 2007;3:e22. https://doi.org/10.1371/journal.ppat.0030022
  38. Kim JH, Lee HO, Cho YJ, et al. A vanillin derivative causes mitochondrial dysfunction and triggers oxidative stress in Cryptococcus neoformans. PLoS One. 2014;9:e89122. https://doi.org/10.1371/journal.pone.0089122
  39. Kim J, Cho YJ, Do E, et al. A defect in iron uptake enhances the susceptibility of Cryptococcus neoformans to azole antifungal drugs. Fungal Genet Biol. 2012;49:955-966. https://doi.org/10.1016/j.fgb.2012.08.006
  40. Sun N, Fonzi W, Chen H, et al. Azole susceptibility and transcriptome profiling in Candida albicans mitochondrial electron transport chain complex I mutants. Antimicrob Agents Chemother. 2013;57:532-542. https://doi.org/10.1128/AAC.01520-12
  41. Stalhberger T, Simenel C, Clavaud C, et al. Chemical organization of the cell wall polysaccharide core of Malassezia restricta. J Biol Chem. 2014; 289:12647-12656. https://doi.org/10.1074/jbc.M113.547034

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