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Reduced Survival and Resistance of Rhodotorula mucilaginosa Following Inhibition of Pigment Production by Naftifine

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Abstract

Pigments produced by micro-organisms could contribute to their pathogenesis and resistance. The investigation into the red pigment of R. mucilaginosa and its ability to survive and resist has not yet been explored. This study aimed to investigate the survival and resistance of the R. mucilaginosa CQMU1 strain following inhibition of pigment production by naftifine and its underlying mechanism. The red-pigmented Rhodotorula mucilaginosa CQMU1 yeast was isolated from an infected toenail of a patient with onychomycosis. Cultivation of R. mucilaginosa in liquid and solid medium showed the effect of naftifine after treatment. Then, analysis of phagocytosis and tolerance to heat or chemicals of R. mucilaginosa was used to evaluate the survival and resistance of yeast to different treatments. Naftifine reversibly inhibited the pigmentation of R. mucilaginosa CQMU1 in solid and liquid media. Depigmented R. mucilaginosa CQMU1 showed increased susceptibility toward murine macrophage cells RAW264.7 and reduced resistance toward different types of chemicals, such as 1.5-M NaCl and 0.5% Congo red. Inhibition of pigment production by naftifine affected the survival and growth of R. mucilaginosa and its resistance to heat and certain chemicals. The results obtained could further elucidate the target of new mycosis treatment.

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Data Availability

The data of this study are presented in the article text and tables. Additional details are available by contacting the corresponding author upon reasonable request. Some data are provided in full in the results sections of this paper and as supplementary data.

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Not applicable.

References

  1. Yang Q, Li Y, Apaliya MT, Zheng X, Serwah BNA, Zhang X, Zhang H (2018) The response of Rhodotorula mucilaginosa to patulin based on lysine crotonylation. Front Microbiol 9:2025. https://doi.org/10.3389/fmicb.2018.02025

    Article  PubMed  PubMed Central  Google Scholar 

  2. Miceli MH, Díaz JA, Lee SA (2011) Emerging opportunistic yeast infections. Lancet Infect Dis 11(2):142–151. https://doi.org/10.1016/S1473-3099(10)70218-8

    Article  PubMed  Google Scholar 

  3. Ioannou P, Vamvoukaki R, Samonis G (2019) Rhodotorula species infections in humans: a systematic review. Mycoses 62(2):90–100. https://doi.org/10.1111/myc.12856

    Article  PubMed  Google Scholar 

  4. Jarros IC, Barros ILE, Prado A, Corrêa JL, Malacrida AM, Negri M, Svidzinski TIE (2022) Rhodotorula sp. and Trichosporon sp. are more virulent after a mixed biofilm. Mycopathologia 187(1):85–93. https://doi.org/10.1007/s11046-021-00606-5

    Article  CAS  PubMed  Google Scholar 

  5. Idris NFB, Huang G, Jia Q, Yuan L, Li Y, Tu Z (2019) Mixed infection of toe nail caused by Trichosporon asahii and Rhodotorula mucilaginosa. Mycopathologia 185:373–376. https://doi.org/10.1007/s11046-019-00406-y

    Article  PubMed  Google Scholar 

  6. Merhan O (2017) Biochemistry and antioxidant properties of carotenoids. Carotenoids 5:51. https://doi.org/10.5772/67592

    Article  CAS  Google Scholar 

  7. Milani A, Basirnejad M, Shahbazi S, Bolhassani A (2017) Carotenoids: biochemistry, pharmacology and treatment. Br J Pharmacol 174(11):1290–1324. https://doi.org/10.1111/bph.13625

    Article  CAS  PubMed  Google Scholar 

  8. Liu GY, Essex A, Buchanan JT, Datta V, Hoffman HM, Bastian JF, Fierer J, Nizet V (2005) Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity. J Exp Med 202(2):209–215. https://doi.org/10.1084/jem.20050846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chen F, Di H, Wang Y, Cao Q, Xu B, Zhang X, Yang N, Liu G, Yang CG, Xu Y, Jiang H, Lian F, Zhang N, Li J, Lan L (2016) Small-molecule targeting of a diapophytoene desaturase inhibits S. aureus virulence. Nat Chem Biol 12(3):174–179. https://doi.org/10.1038/nchembio.2003

    Article  CAS  PubMed  Google Scholar 

  10. Moliné M, Flores MR, Libkind D et al (2010) Photoprotection by carotenoid pigments in the yeast Rhodotorula mucilaginosa: the role of torularhodin. Photochem Photobiol Sci 9:1145–1151. https://doi.org/10.1039/c0pp00009d

    Article  CAS  PubMed  Google Scholar 

  11. Zelver N, Hamilton M, Pitts B, Goeres D, Walker D, Sturman P, Heersink J (1999) Measuring antimicrobial effects on biofilm bacteria: from laboratory to field. Methods Enzymol 310:608–628. https://doi.org/10.1016/s0076-6879(99)10047-8

    Article  CAS  PubMed  Google Scholar 

  12. Tuon FF, Costa SF (2008) Rhodotorula infection. A systematic review of 128 cases from literature. Rev Iberoam Micol 25:135–140. https://doi.org/10.1016/s1130-1406(08)70032-9

    Article  PubMed  Google Scholar 

  13. Davoli P, Mierau V, Weber RWS (2004) Carotenoids and fatty acids in red yeasts Sporobolomyces roseus and Rhodotorula glutinis. Appl Microbiol Biotechnol 40:392–397. https://doi.org/10.1023/B:ABIM.0000033917.57177.f2

    Article  CAS  Google Scholar 

  14. Moț AC, Pârvu M, Pârvu AE, Roşca-Casian O, Dina NE, Leopold N, Silaghi-Dumitrescu R, Mircea C (2017) Reversible naftifine-induced carotenoid depigmentation in Rhodotorula mucilaginosa (A. Jörg.) FC Harrison causing onychomycosis. Sci Rep 7(1):1–12. https://doi.org/10.1038/s41598-017-11600-7

    Article  CAS  Google Scholar 

  15. Li B, Ni S, Chen F, Mao F, Wei H, Liu Y et al (2018) Discovery of potent benzocycloalkane derived diapophytoene desaturase inhibitors with an enhanced safety profile for the treatment of MRSA. VISA, and LRSA infections. ACS Infect Dis 4:208–217. https://doi.org/10.1016/j.ejmech.2017.12.090

    Article  CAS  PubMed  Google Scholar 

  16. Huang G, Idris NFB, Li Y, Wang Y, Tu Z (2020) Naftifine inhibits pigmentation through down-regulation on expression of phytoene desaturase gene CAR1 in Rhodotorula mucilaginosa. Afr J Microbiol Res 14(5):166–174. https://doi.org/10.5897/AJMR2020.9316

    Article  CAS  Google Scholar 

  17. Padyana AK, Gross S, Jin L, Cianchetta G, Narayanaswamy R, Wang F, Wang R, Fang C, Lv X, Biller SA, Dang L, Mahoney CE, Nagaraja N, Pirman D, Sui Z, Popovici-Muller J, Smolen GA (2019) Structure and inhibition mechanism of the catalytic domain of human squalene epoxidase. Nat Commun 10:97. https://doi.org/10.1038/s41467-018-07928-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Nosanchuk JD, Casadevall A (2006) Impact of melanin on microbial virulence and clinical resistance to antimicrobial compounds. Antimicrob Agents Chemother 50:3519–3528. https://doi.org/10.1128/AAC.00545-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Jahn B et al (1997) Isolation and characterization of a pigmentless-conidium mutant of Aspergillus fumigatus with altered conidial surface and reduced virulence. Infect Immun 12:5110–5117. https://doi.org/10.1128/iai.65.12.5110-5117.1997

    Article  Google Scholar 

  20. Pihet M et al (2009) Melanin is an essential component for the integrity of the cell wall of Aspergillus fumigatus conidia. BMC Microbiol 9:177. https://doi.org/10.1186/1471-2180-9-177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Koselny K, Mutlu N, Minard AY, Kumar A, Krysan DJ, Wellington M (2018) A genome-wide screen of deletion mutants in the filamentous Saccharomyces cerevisiae background identifies ergosterol as a direct trigger of macrophage pyroptosis. MBio 9(4):e01204-e1218. https://doi.org/10.1128/mBio.01204-18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Schroeder WA, Johnson EA (1993) Antioxidant role of carotenoids in Phaffia rhodozyma. J Ind Microbiol Biotechnol 139:907–912. https://doi.org/10.1099/00221287-139-5-907

    Article  CAS  Google Scholar 

  23. Kejžar A, Gobec S, Plemenitaš A, Lenassi M (2013) Melanin is crucial for growth of the black yeast Hortaea werneckii in its natural hypersaline environment. Fungal Biol 117(5):368–379. https://doi.org/10.1016/j.funbio.2013.03.006

    Article  CAS  PubMed  Google Scholar 

  24. Leber R, Landl K, Zinser E, Ahorn H, Spok A, Kohlwein SD, Turnowsky F, Daum G (1998) Dual localization of squalene epoxidase, SQLE protein, in yeast reflects a relationship between the endoplasmic reticulum and lipid particles. Mol Biol Cell 9:375–386. https://doi.org/10.1091/mbc.9.2.375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wentzinger LF, Bach TJ, Hartmann MA (2002) Inhibition of squalene synthase and squalene epoxidase in tobacco cells triggers an up-regulation of 3-hydroxy-3-methylglutaryl coenzyme a reductase. Plant Physiol 130:334–346. https://doi.org/10.1104/pp.004655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gill S, Stevenson J, Kristiana I, Brown AJ (2011) Cholesterol-dependent degradation of squalene monooxygenase, a control point in cholesterol synthesis beyond HMG-CoA reductase. Cell Metab 13(3):260–273. https://doi.org/10.1016/j.cmet.2011.01.015

    Article  CAS  PubMed  Google Scholar 

  27. Germann M, Gallo C, Donahue T, Shirzadi R et al (2005) Characterizing sterol defect suppressors uncovers a novel transcriptional signaling pathway regulating zymosterol biosynthesis. J Biol Chem 280:35904–35913. https://doi.org/10.1074/jbc.M504978200

    Article  CAS  PubMed  Google Scholar 

  28. Rosas AL, Casadevall A (1997) Melanization affects susceptibility of Cryptococcus neoformans to heat and cold. FEMS Microbiol Lett 153:265–272

    Article  CAS  PubMed  Google Scholar 

  29. Paolo WF, Dadachova E, Mandal P et al (2006) Effects of disrupting the polyketide synthase gene WdPKS1 in Wangiella [Exophiala] dermatitidis on melanin production and resistance to killing by antifungal compounds, enzymatic degradation, and extremes in temperature. BMC Microbiol 6:55. https://doi.org/10.1186/1471-2180-6-55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Agustinho DP, and Nosanchuk J (2017). Functions of Fungal Melanins. In book Reference Module in Life Science. https://doi.org/10.1016/B978-0-12-809633-8.12091-6.

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Acknowledgements

We are grateful to The first Affiliated Hospital of Chongqing Medical University for providing the clinical isolates and laboratory equipment.

Funding

This research was funded by Chongqing Research Program of Basic Research and Frontier Technology [Grant No. cstc2021jcyj-msxmX0158], and Scientific and Technological Research Program of Chongqing Municipal Education Commission [Grant No. KJQN202113201]. The funding bodies had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

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Authors and Affiliations

  1. Department of pathogen biology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China

    Nur Fazleen Binti Idris, He Lu, Yanan Guo, Yang Wang, Rui Hao & Zeng Tu

  2. Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

    Qianying Jia

  3. Chongqing Nursing Vocational College, Chongqing, 402763, China

    Qianying Jia

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  1. Nur Fazleen Binti Idris
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Contributions

NFBI performed the experiments (lead), analyzed the data (lead), and wrote the original draft of the manuscript (lead). QJ (supporting) and HL (supporting) conducted sampling and sample identification, and YG (supporting) and WY provided assistance in the purchase of chemicals (lead) and culture media preparation (supporting). H provided assistance with the generation of graphical data (supporting) and manuscript editing. TZ designed the study (lead) and supervised the work (lead) and was responsible for conceptualization (lead), data curation (lead), funding acquisition (lead), and methodology formulation (lead). All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Zeng Tu.

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Conflict of interest

The author(s) declare no conflicts of interest.

Ethical Approval

The Ethics Committee of Chongqing Medical University has approved this study as reference number 2020211 and the approval was given on 10th October 2020.

Informed Consent

Informed consent was obtained from all individual participants, authors, and patients, included in the study.

Consent to Participations

The patient of Chongqing Medical University has given the consent to participate in this study as approved by the Ethics Committee of Chongqing Medical University given on 10th October 2020 with reference number 2020011.

Consent for Publications

The Ethics Committee of Chongqing Medical University has approved this study as reference number 2020211 and the data obtained can be published in this journal.

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Idris, N.F.B., Jia, Q., Lu, H. et al. Reduced Survival and Resistance of Rhodotorula mucilaginosa Following Inhibition of Pigment Production by Naftifine. Curr Microbiol 80, 285 (2023). https://doi.org/10.1007/s00284-023-03388-9

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