In vitro effects of quorum sensing molecules (Tryptophol) on the growth of antifungal drug-resistant fungi

Authors

  • Watcharamat Muangkaew Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University
  • Nicha Ruenmul Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University
  • Pornpan Khum-em Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University
  • Thitinan Kitisin Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University
  • Passanesh Sukphopetch Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University

Keywords:

fungal quorum sensing molecules, tryptophan, fibroblast cells, cytotoxicity cells

Abstract

Abstract
Human pathogenic fungi such as Candida spp. and Aspergillus spp. have been shown to increase the frequency of antifungal resistance, especially in the Azole group. The previous study found that tryptophol, which is classified as fungal quorum sensing molecules (QSMs), plays a role in fungal growth inhibition. Therefore, in the present study aimed to investigate the potential of tryptophol to control the growth of both drug susceptibility and Azole resistant strains of C. albicans and A. fumigatus in vitro, as well as to evaluate the inhibitory concentration of tryptophol on the cytotoxicity of fibroblast cells. This study results showed that tryptophol at the Minimum Inhibitory Concentration (MIC) of 2 mM and 8 mM was able to inhibit the growth of C.albicans and A. fumigatus, respectively. In addition, tryptophol at concentrations of 2 mM and 4 mM did not cause damage to mitochondria and cytotoxicity after treatment with fibroblast cells by MTT Assay. The percentage of cell viability was 113.86±9.34% and 105.08±13.66%, respectively. However, tryptophol at a concentration of 8 mM can produce a cytotoxic effect. When examining the apoptosis of fibroblast cells using Ethidium Bromide-Acridine Orange Staining Assay, we found that tryptophol at concentrations of 2 mM and 4 mM was able to induce fibroblast apoptosis by 46% and 40.2%, respectively. Tryptophol at concentrations of 8 to 64 mM and was able to induce 100% of fibroblast cell apoptosis. Moreover, tryptophol at concentrations of 2 mM and 4 mM was able to down-regulate the expression of Caspase-8 andCARD-9 genes and to up-regulate the Caspase-8 andCARD-9 genes when treated at concentrations of 8 to 64 mM. From the results, this study showed that the tryptophol at a concentration of 8mM was capable of inhibiting growth both drug susceptibility and Azole resistant strains of C. albicans and A. fumigatus. However, the utilization of tryptophol is limited to fibroblast cells in the induction of cell apoptosis.

References

Sahni K, Singh S, Dogra S. Newer topical treatments in skin and nail dermatophyte infections. Indian J Dermatol 2018;9:149-58.

Fisher MC, Hawkins NJ, Sanglard D, et al. Worldwide emergence of resistance to antifungal drugs challenges human health and food security. Science 2018;360:739-42.

Lam JM. Opportunistic fungal infection in children and management. Curr Opin Pediatr 2018;30:514-9.

Oltolini C, Ripa M, Andolina A, et al. Invasive pulmonary Aspergillosis complicated by carbapenem-resistant Pseudomonas aeruginosa infection during pembrolizumab immunotherapy for metastatic lung adenocarcinoma: Case report and review of the literature. Mycopathologia 2019;184:181-5.

Walsh TJ, Katragkou A, Chen T, et al. Invasive candidiasis in infants and children: Recent advances in epidemiology, diagnosis, and treatment. J Fungi (Basel) 2019;5:1-9.

Spampinato C, Leonardi D. Candida infections, causes, targets, and resistance mechanisms: traditional and alternative antifungal agents. Biomed Res Int 2013;2013:1-13.

Arendrup MC, Patterson TF. Multidrugresistant Candida: epidemiology, molecular mechanisms and treatment. J Infect Dis 2017;216:S445-51.

Whaley SG, Berkow EL, Rybak JM, et al. Azole antifungal resistance in Candida albicans and emerging non-albicans Candida species. Front Microbiol 2017;7:1-12.

Gao J, Wang H, Li Z, et al. Candida albicans gains azole resistance by altering sphingolipid composition. Nat Commun 2018;9:1-15.

Latge JP. The pathobiology of Aspergillus fumigatus. Trends Microbiol 2001;9:382-9.

Sugui JA, Kwon-Chung KJ, Juvvadi PR, et al. Aspergillus fumigatus and related species. Cold Spring Harb Perspect Med 2015;5:1-18.

Latge JP. Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev 1999;12: 310-50.

Blum G, Hortnagl C, Jukic E, et al. New insight into amphotericin B resistance in Aspergillus terreus. Antimicrob Agents Ch 2013;57:1583-8.

Kemoi EK, Nyerere A, Bii CC. TriazoleResistant Aspergillus fumigatus from Fungicide-experienced soils in Naivasha subcounty and Nairobi county, Kenya. Int J Microbiol 2018;2018:1-6.

Berger S, El Chazli Y, Babu AF, et al. Azole Resistance in Aspergillus fumigatus: A consequence of antifungal use in agriculture?. Front microbiol 2017;8:1-7.

Tangwattanachuleeporn M, Minarin N, Saichan S, et al. Prevalence of azoleresistant Aspergillus fumigatus in the environment of Thailand. Medical Mycology 2017;55:429-35.

Walker TA, Lockhart SR, Beekmann SE, et al. Recognition of azole-resistant Aspergillosis by physicians specializing in infectious diseases, United States. Emerg Infect Dis 2018;24:111-3.

Abisado RG, Benomar S, Klaus JR, et al. Bacterial quorum sensing and microbial community interactions. MBio 2018;9:1-13.

Albuquerque P, Casadevall A. Quorum sensing in fungi a review. Med Mycol 2012;50:337-45.

Padder SA, Prasad R, Shah AH. Quorum sensing: A less known mode of communication among fungi. Microbiol Res 2018;210:51-8.

Barriuso J. Quorum sensing mechanisms in fungi. Aims Microbiol 2015;1:37-47.

Hogan DA. Talking to themselves: Autoregulation and quorum sensing infungi. Eukaryot Cell 2006;5:613-9.

Hornby JM, Jacobitz-Kizzier SM, McNeel DJ, et al. Inoculum size effect in dimorphic fungi: Extracellular control of yeastmycelium dimorphism in Ceratocystis ulmi. Appl Environ Microb 2004;70:1356-9.

Nadal M, Garcia-Pedrajas MD, Gold SE. Dimorphism in fungal plant pathogens. Fems Microbiol Lett 2008;284:127-34.

Wongsuk T, Pumeesat P, Luplertlop N. Fungal quorum sensing molecules: Role in fungal morphogenesis and pathogenicity.J Basic Microbiol 2016;56:440-7.

Rosazza JP, Juhl R, Davis P. Tryptophol formation by Zygosaccharomyces priorianus. Appl Microbiol 1973;26:98-105.

Valera MJ, Morcillo-Parra MA, Zagorska I, et al. Effects of melatonin and tryptophol addition on fermentations carried out by Saccharomyces cerevisiae and nonSaccharomyces yeast species under

different nitrogen conditions. Int J Food Microbiol 2019;289:174-81.

Chen H, Fink GR. Feedback control of morphogenesis in fungi by aromatic alcohols. Genes Dev 2006;20:1150-61.

De Sordi L, Muhlschlegel FA. Quorum sensing and fungal-bacterial interactions in Candida albicans: A communicative network regulating microbial coexistence and virulence. FEMS Yeast Res 2009;9:990-9.

Gori K, Knudsen PB, Nielsen KF, et al. Alcohol-based quorum sensing plays a role in adhesion and sliding motility of the yeast Debaryomyces hansenii. FEMS Yeast Res 2011;11:643-52.

Verbrugghe E, Adriaensen C, Martel A, et al. Growth regulation in Amphibian pathogenic chytrid fungi by the quorum sensing metabolite Tryptophol. Front Microbiol 2019;9:1-12.

Chen H, Fink GR. Feedback control of morphogenesis in fungi by aromatic alcohols. Gene Dev 2006;20:1150-61.

Tamura T, Asahara M, Yamamoto M, et al. In vitro susceptibility of dermatomycoses agents to six antifungal drugs and evaluation by fractional inhibitory concentration index of combined effects of amorolfine and itraconazole in dermatophytess. Microbiol Immunol

;58:1-8.

Adimi P, Hashemi SJ, Mahmoudi M, et al. In-vitro Activity of 10 antifungal agents against 320 dermatophytes strains using

microdilution method in Tehran. Iran J Pharm Res 2013;12:537-45.

Baygar T, Sarac N, Ugur A, et al. Antimicrobial characteristics and biocompatibility of the surgical sutures coated with biosynthesized

silver nanoparticles. Bioorg Chem 2018;86: 254-8.

Sibiya MA, Raphoko L, Mangokoana D, et al. Induction of cell death in human A549 cells using 3-(Quinoxaline-3-yl) prop-2-ynyl methanosulphonate and

-(Quinoxaline-3-yl) prop-2-yn-1-ol. Molecules 2019;24:1-16.

Sutabhaha B. Laboratory identification of pathogenic fungi. 3rd ed. Chiang Mai: Darawan printing ltd; 2009.

Wongsuk T, Sukphopetch P. Effect of quarum sensing molecules on Aspergillus fumigatus. Walailak J Sci & Tech 2020;17: 348-58.

Liu K, Liu P C, Liu R, et al. Dual AO/EB staining to detect apoptosis in Osteosarcoma cells compared with flow cytometry. Med Sci Monit Basic Res 2015;21:15-20.

Downloads

Published

2022-08-31

How to Cite

1.
Muangkaew W, Ruenmul N, Khum-em P, Kitisin T, Sukphopetch P. In vitro effects of quorum sensing molecules (Tryptophol) on the growth of antifungal drug-resistant fungi. J Med Health Sci [Internet]. 2022 Aug. 31 [cited 2024 Mar. 29];29(2). Available from: https://he01.tci-thaijo.org/index.php/jmhs/article/view/258412