Abstract
Candida auris is an emerging pathogen that has caused numerous severe infections in recent years, and has therefore become a global concern for public health agencies. Most conventional antifungal agents, especially fluconazole, have shown limited effects on this pathogen. New methods to restrict this pathogen are in urgent demand. Antimicrobial photodynamic therapy (aPDT) has been shown to be a promising technique against multiple pathogenic fungi. This study sought to determine the in vitro effect of aPDT using methylene blue (MB) combined with light-emitting diode (LED) on the viability of planktonic cells and biofilms of five clinical strains of C. auris. MB (8, 16 and 32 μg/ml) was applied as the photosensitizer, and a LED (635 nm, 12 and 24 J/cm2) device was used as light source to activate the photosensitizer. The results showed that there was no growth of tested C. auris strains following aPDT on planktonic cultures. In addition, aPDT exhibited colony-forming unit reduction of up to 7.20 log10 against C. auris biofilms. These data demonstrate that in vitro aPDT with MB and LED offers promising potential for the treatment of C. auris infections.
Similar content being viewed by others
References
Satoh K, Makimura K, Hasumi Y, Nishiyama Y, Uchida K, Yamaguchi H. Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol Immunol. 2009;53:41–4. https://doi.org/10.1111/j.1348-0421.2008.00083.x.
Cortegiani A, Misseri G, Fasciana T, Giammanco A, Giarratano A, Chowdhary A. Epidemiology, clinical characteristics, resistance, and treatment of infections by Candida auris. J Intensive Care. 2018;6:69. https://doi.org/10.1186/s40560-018-0342-4.
Biswal M, Rudramurthy SM, Jain N, Shamanth AS, Sharma D, Jain K, et al. Controlling a possible outbreak of Candida auris infection: lessons learnt from multiple interventions. J Hosp Infect. 2017;97:363–70. https://doi.org/10.1016/j.jhin.2017.09.009.
Schelenz S, Hagen F, Rhodes JL, Abdolrasouli A, Chowdhary A, Hall A, et al. First hospital outbreak of the globally emerging Candida auris in a European hospital. Antimicrob Resist Infect Control. 2016;5:35. https://doi.org/10.1186/s13756-016-0132-5.
Chowdhary A, Voss A, Meis JF. Multidrug-resistant Candida auris: ‘new kid on the block’ in hospital-associated infections? J Hosp Infect. 2016;94:209–12. https://doi.org/10.1016/j.jhin.2016.08.004.
England PH. Guidance for the laboratory investigation, management and infection prevention and control for cases of Candida auris. London: Public Health England; 2017.
Lepak AJ, Zhao M, Berkow EL, Lockhart SR, Andes DR. Pharmacodynamic optimization for treatment of invasive Candida auris infection. Antimicrob Agents Chemother. 2017;61:e00791-17. https://doi.org/10.1128/aac.00791-17.
Vallabhaneni S, Kallen A, Tsay S, Chow N, Welsh R, Kerins J, et al. Investigation of the First Seven Reported Cases of Candida auris, a Globally Emerging Invasive, Multidrug-Resistant Fungus-United States, May 2013-August 2016. Am J Transplant. 2017;17:296–9. https://doi.org/10.1111/ajt.14121.
Sharma C, Kumar N, Pandey R, Meis JF, Chowdhary A. Whole genome sequencing of emerging multidrug resistant Candida auris isolates in India demonstrates low genetic variation. New Microbes New Infect. 2016;13:77–82. https://doi.org/10.1016/j.nmni.2016.07.003.
Das S, Rai G, Tigga RA, Srivastava S, Singh PK, Sharma R, et al. Candida auris in critically ill patients: emerging threat in intensive care unit of hospitals. J Mycol Med. 2018;28:514–8. https://doi.org/10.1016/j.mycmed.2018.06.005.
Chowdhary A, Sharma C, Duggal S, Agarwal K, Prakash A, Singh PK, et al. New clonal strain of Candida auris, Delhi, India. Emerg Infect Dis. 2013;19:1670–3. https://doi.org/10.3201/eid1910.130393.
Kathuria S, Singh PK, Sharma C, Prakash A, Masih A, Kumar A, et al. Multidrug-resistant Candida auris misidentified as Candida haemulonii: characterization by matrix-assisted laser desorption ionization-time of flight mass spectrometry and DNA sequencing and its antifungal susceptibility profile variability by Vitek 2, CLSI broth microdilution, and etest method. J Clin Microbiol. 2015;53:1823–30. https://doi.org/10.1128/JCM.00367-15.
Azar MM, Turbett SE, Fishman JA, Pierce VM. Donor-derived transmission of Candida auris during lung transplantation. Clin Infect Dis. 2017;65:1040–2. https://doi.org/10.1093/cid/cix460.
Rajendran R, Sherry L, Nile CJ, Sherriff A, Johnson EM, Hanson MF, et al. Biofilm formation is a risk factor for mortality in patients with Candida albicans bloodstream infection-Scotland, 2012–2013. Clin Microbiol Infect. 2016;22:87–93. https://doi.org/10.1016/j.cmi.2015.09.018.
Borman AM, Szekely A, Johnson EM. Comparative pathogenicity of United Kingdom isolates of the emerging pathogen Candida auris and other key pathogenic Candida species. mSphere. 2016;1:e00189-16. https://doi.org/10.1128/msphere.00189-16.
Kean R, Delaney C, Sherry L, Borman A, Johnson EM, Richardson MD, et al. Transcriptome assembly and profiling of Candida auris reveals novel insights into biofilm-mediated resistance. mSphere. 2018;3:e00334-18. https://doi.org/10.1128/msphere.00334-18.
Wainwright M, Maisch T, Nonell S, Plaetzer K, Almeida A, Tegos GP, et al. Photoantimicrobials-are we afraid of the light? Lancet Infect Dis. 2017;17:e49–55. https://doi.org/10.1016/S1473-3099(16)30268-7.
Baltazar LM, Ray A, Santos DA, Cisalpino PS, Friedman AJ, Nosanchuk JD. Antimicrobial photodynamic therapy: an effective alternative approach to control fungal infections. Front Microbiol. 2015;6:202. https://doi.org/10.3389/fmicb.2015.00202.
Gao L, Jiang S, Sun Y, Deng M, Wu Q, Li M, et al. Evaluation of the effects of photodynamic therapy alone and combined with standard antifungal therapy on planktonic cells and biofilms of Fusarium spp. and Exophiala spp. Front Microbiol. 2016;7:617. https://doi.org/10.3389/fmicb.2016.00617.
Pires L, Bosco Sde M, Baptista MS, Kurachi C. Photodynamic therapy in Pythium insidiosum—an in vitro study of the correlation of sensitizer localization and cell death. PLoS ONE. 2014;9:e85431. https://doi.org/10.1371/journal.pone.0085431.
Lyon JP, Moreira LM, de Carvalho VS, dos Santos FV, de Lima CJ, de Resende MA. In vitro photodynamic therapy against Foncecaea pedrosoi and Cladophialophora carrionii. Mycoses. 2013;56:157–61. https://doi.org/10.1111/j.1439-0507.2012.02226.x.
Pereira Gonzales F, Maisch T. Photodynamic inactivation for controlling Candida albicans infections. Fungal Biol. 2012;116:1–10. https://doi.org/10.1016/j.funbio.2011.10.001.
Pierce CG, Uppuluri P, Tristan AR, Wormley FL Jr, Mowat E, Ramage G, et al. A simple and reproducible 96-well plate-based method for the formation of fungal biofilms and its application to antifungal susceptibility testing. Nat Protoc. 2008;3:1494–500. https://doi.org/10.1038/nport.2008.141.
Dai T, Fuchs BB, Coleman JJ, Prates RA, Astrakas C, St Denis TG, et al. Concepts and principles of photodynamic therapy as an alternative antifungal discovery platform. Front Microbiol. 2012;3:120. https://doi.org/10.3389/fmicb.2012.00120.
Abrahamse H, Hamblin MR. New photosensitizers for photodynamic therapy. Biochem J. 2016;473:347–64. https://doi.org/10.1042/BJ20150942.
Lopes M, Alves CT, Rama Raju B, Goncalves MS, Coutinho PJ, Henriques M, et al. Application of benzo[a]phenoxazinium chlorides in antimicrobial photodynamic therapy of Candida albicans biofilms. J Photochem Photobiol B. 2014;141:93–9. https://doi.org/10.1016/j.jphotobiol.2014.09.006.
Liu S, Qiao S, Li L, Qi G, Lin Y, Qiao Z, et al. Surface charge-conversion polymeric nanoparticles for photodynamic treatment of urinary tract bacterial infections. Nanotechnology. 2015;26:495602. https://doi.org/10.1088/0957-4484/26/49/495602.
Donnelly RF, McCarron PA, Tunney MM, David Woolfson A. Potential of photodynamic therapy in treatment of fungal infections of the mouth. Design and characterisation of a mucoadhesive patch containing toluidine blue O. J Photochem Photobiol B. 2007;86:59–69. https://doi.org/10.1016/j.jphotobiol.2006.07.011.
Ribeiro AP, Andrade MC, da Silva Jde F, Jorge JH, Primo FL, Tedesco AC, et al. Photodynamic inactivation of planktonic cultures and biofilms of Candida albicans mediated by aluminum-chloride-phthalocyanine entrapped in nanoemulsions. Photochem Photobiol. 2013;89:111–9. https://doi.org/10.1111/j.1751-1097.2012.01198.x.
Rosseti IB, Chagas LR, Costa MS. Photodynamic antimicrobial chemotherapy (PACT) inhibits biofilm formation by Candida albicans, increasing both ROS production and membrane permeability. Lasers Med Sci. 2014;29:1059–64. https://doi.org/10.1007/s10103-013-1473-4.
Acknowledgements
We gratefully acknowledge Professor Haoping Liu from University of California, Irvine, for kindly providing us with isolates studied.
Funding
This work was supported by National Natural Science Foundation of China (31400131 to Lujuan Gao and 81401677 to Yi Sun), Natural Science Foundation of Shanghai (16ZR1431300 to Jingwen Tan), Shanghai Municipal Commission of Health and Family Planning (20154Y0196 to Jingwen Tan) and Fundamental Research Funds for the Central Universities (22120180341 to Jingwen Tan).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Handling Editor: Mariana Henriques.
Rights and permissions
About this article
Cite this article
Tan, J., Liu, Z., Sun, Y. et al. Inhibitory Effects of Photodynamic Inactivation on Planktonic Cells and Biofilms of Candida auris. Mycopathologia 184, 525–531 (2019). https://doi.org/10.1007/s11046-019-00352-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11046-019-00352-9