Effect of Quarum Sensing Molecules on Aspergillus fumigatus


  • Thanwa WONGSUK Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
  • Passanesh SUKPHOPETCH Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand




Quorum sensing molecules, Aspergillus fumigatus, biofilms, minimum inhibitory concentration


Aspergillus fumigatus is an opportunistic fungal pathogen to which immunocompromised patients are especially susceptible. A. fumigatus can form biofilms both in vitro and in vivo. Quorum sensing molecules (QSMs) have activity against some fungi. This study aimed to determine the activity of the QSMs farnesol, tyrosol, phenylethanol and tryptophol against the growth A. fumigatus on solid media, and against its ability to form biofilms. The activity of each QSM against planktonic A. fumigatus growth was assessed using the CLSI M38-A2 broth microdilution assay, while QSM inhibition of A. fumigatus’s biofilm formation was measured in crystal violet, and 2, 3-bis (2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-caboxanilide (XTT) assays. The QSMs reduced the colony diameter of the studied strains in a QSM-dependent pattern. Tryptophol showed the best effect and tyrosol showed the poorest effect. The minimum inhibitory concentrations (MICs) for farnesol, tyrosol, phenylethanol and tryptophol tested against A. fumigatus were > 32, > 32, 16 and 8 mM, respectively. The effective concentration each QSM required to inhibit A. fumigatus biofilm formation were higher than the planktonic MICs. In this study, the performance of QSMs against A. fumigatus ranked from best to worst as follows: tryptophol, phenylethanol, farnesol and tyrosol. Because of phenylethanol and tryptophol showed the strongest effect to the growth and biofilm formation of A. fumigatus. Therefore, the cytotoxic activities of phenylethanol and tryptophol in A549 cells (lung alveolar epithelial cells) were determined. However, phenylethanol and tryptophol induced A549 cell damage (at MIC level), as demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) and lactate dehydrogenase (LDH) assays.


Download data is not yet available.


Metrics Loading ...

Author Biographies

Thanwa WONGSUK, Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand

Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University.

420/6 Ratchawithi Rd., Ratchathewi, Bangkok 10400 

Passanesh SUKPHOPETCH, Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand

Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University.

420/6 Ratchawithi Rd., Ratchathewi, Bangkok 10400 


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

KW Nickerson, AL Atkin and JM Hornby. Quorum sensing in dimorphic fungi: Farnesol and beyond. Appl. Environ. Microbiol. 2006; 72, 3805-13.

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

NA Gow, AJ Brown and FC Odds. Fungal morphogenesis and host invasion. Curr. Opin. Microbiol. 2002; 5, 366-71.

RA Hall, KJ Turner, J Chaloupka, F Cottier, LD Sordi, D Sanglard, LR Levin, J Buck and FA Mühlschlegel. The quorum-sensing molecules farnesol/homoserine lactone and dodecanol operate via distinct modes of action in Candida albicans. Eukaryot. Cell. 2011; 10, 1034-42.

BW Kebaara, ML Langford, DH Navarathna, R Dumitru, KW Nickerson and AL Atkin. Candida albicans Tup1 is involved in farnesol-mediated inhibition of filamentous-growth induction. Eukaryot. Cell. 2008; 7, 980-7.

M Kruppa, BP Krom, N Chauhan, AV Bambach, RL Cihlar and RA Calderone. The two-component signal transduction protein Chk1p regulates quorum sensing in Candida albicans. Eukaryot. Cell. 2004; 3, 1062-5.

DD Mosel, R Dumitru, JM Hornby, AL Atkin and KW Nickerson. Farnesol concentrations required to block germ tube formation in Candida albicans in the presence and absence of serum. Appl. Environ. Microbiol. 2005; 71, 4938-40.

P Sudbery, N Gow and J Berman. The distinct morphogenic states of Candida albicans. Trends Microbiol. 2004; 12, 317-24.

CP Semighini, JM Hornby, R Dumitru, KW Nickerson and SD Harris. Farnesol-induced apoptosis in Aspergillus nidulans reveals a possible mechanism for antagonistic interactions between fungi. Mol. Microbiol. 2006; 59, 753-64.

M Savoldi, I Malavazi, FM Soriani, JL Capellaro, K Kitamoto, MES Ferreira, MH Goldman and GH Goldman. Farnesol induces the transcriptional accumulation of the Aspergillus nidulans Apoptosis-Inducing Factor (AIF)-like mitochondrial oxidoreductase. Mol. Microbiol. 2008; 70, 44-59.

J Lorek, S Poggeler, MR Weide, R Breves and DP Bockmuhl. Influence of farnesol on the morphogenesis of Aspergillus niger. J. Basic Microbiol. 2008; 48, 99-103.

X Wang, Y Wang, Y Zhou and X Wei. Farnesol induces apoptosis-like cell death in the pathogenic fungus Aspergillus flavus. Mycologia 2014; 106, 881-8.

K Dichtl, F Ebel, F Dirr, FH Routier, J Heesemann and J Wagener. Farnesol misplaces tip-localized Rho proteins and inhibits cell wall integrity signalling in Aspergillus fumigatus. Mol. Microbiol. 2010; 76, 1191-204.

MA Alem, MD Oteef, TH Flowers and LJ Douglas. Production of tyrosol by Candida albicans biofilms and its role in quorum sensing and biofilm development. Eukaryot. Cell. 2006; 5, 1770-9.

AR Cordeiro, CE Teixeira, RS Brilhante, DS Castelo-Branco, LP Alencar, JSD Oliveira, AJ Monteiro, TJ Bandeira, JJ Sidrim, JL Moreira and MF Rocha. Exogenous tyrosol inhibits planktonic cells and biofilms of Candida species and enhances their susceptibility to antifungals. FEMS Yeast Res. 2015; 15, fov012.

S Shanmughapriya, H Sornakumari, A Lency, S Kavitha and K Natarajaseenivasan. Synergistic effect of amphotericin B and tyrosol on biofilm formed by Candida krusei and Candida tropicalis from intrauterine device users. Med. Mycol. 2014; 52, 853-61.

BT Lingappa, M Prasad, Y Lingappa, DF Hunt and K Biemann. Phenethyl alcohol and tryptophol: autoantibiotics produced by the fungus Candida albicans. Science 1969; 163, 192-4.

S Ghosh, BW Kebaara, AL Atkin and KW Nickerson. Regulation of aromatic alcohol production in Candida albicans. Appl. Environ. Microbiol. 2008; 74, 7211-8.

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

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

S Bruns, M Seidler, D Albrecht, S Salvenmoser, N Remme, C Hertweck, AA Brakhage, O Kniemeyer and FM Müller. Functional genomic profiling of Aspergillus fumigatus biofilm reveals enhanced production of the mycotoxin gliotoxin. Proteomics 2010; 10, 3097-107.

C Loussert, C Schmitt, MC Prevost, V Balloy, E Fadel, B Philippe, C Kauffmann-Lacroix, JP Latgé and A Beauvais. In vivo biofilm composition of Aspergillus fumigatus. Cell Microbiol. 2010; 12, 405-10.

E Mowat, J Butcher, S Lang, C Williams and G Ramage. Development of a simple model for studying the effects of antifungal agents on multicellular communities of Aspergillus fumigatus. J. Med. Microbiol. 2007; 56, 1205-12.

E Mowat, S Lang, C Williams, E McCulloch, B Jones and G Ramage. Phase-dependent antifungal activity against Aspergillus fumigatus developing multicellular filamentous biofilms. J. Antimicrob. Chemother 2008; 62, 1281-4.

G Ramage, E Mowat, B Jones, C Williams and J Lopez-Ribot. Our current understanding of fungal biofilms. Crit. Rev. Microbiol. 2009; 35, 340-55.

G Ramage, R Rajendran, M Gutierrez-Correa, B Jones and C Williams. Aspergillus biofilms: Clinical and industrial significance. FEMS Microbiol. Lett. 2011; 324, 89-97.

FLVD Veerdonk, MS Gresnigt, L Romani, MG Netea and JP Latge. Aspergillus fumigatus morphology and dynamic host interactions. Nat. Rev. Microbiol. 2017; 15, 661-74.

E Mowat, C Williams, B Jones, S McChlery and G Ramage. The characteristics of Aspergillus fumigatus mycetoma development: Is this a biofilm? Med. Mycol. 2009; 47, S120-6.

CG Pierce, P Uppuluri, AR Tristan, FLJ Wormley, E Mowat, G Ramage and JL Lopez-Ribot. 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.

JH Rex, BD Alexander and D Andes. Reference Method for Broth Dilutions Antifungal Susceptibility Testing of Filamentous Fungi. 2nd ed. Approved Stamdard, M38-A2. Wayne: Clinical and Laboratory Standards Institute, 2008.

LS Derengowski, C De-Souza-Silva, SV Braz, TM Mello-De-Sousa, SN Bao, CM Kyaw and I Silva-Pereira. Antimicrobial effect of farnesol, a Candida albicans quorum sensing molecule, on Paracoccidioides brasiliensis growth and morphogenesis. Ann. Clin. Microbiol. Antimicrob. 2009; 8, 13.

RS Brilhante, RAD Lima, EP Caetano, JJ Leite, DS Castelo-Branco, JF Ribeiro, JT Bandeira, AR Cordeiro, AJ Monteiro, JJ Sidrim and MF Rocha. Effect of farnesol on growth, ergosterol biosynthesis, and cell permeability in Coccidioides posadasii. Antimicrob. Agents Chemother. 2013; 57, 2167-70.

RS Brilhante, EP Caetano, RA Lima, FJ Marques, DS Castelo-Branco, CV Melo, GMM Guedes, JS Oliveira, ZP Camargo, JLB Moreira, AJ Monteiro, TJPG Bandeira, RA Cordeiro, MFG Rocha and JJC Sidrima. Terpinen-4-ol, tyrosol, and beta-lapachone as potential antifungals against dimorphic fungi. Braz. J. Microbiol. 2016; 47, 917-24.

RA Cordeiro, CE Teixeira, RS Brilhante, DS Castelo-Branco, MA Paiva, JJG Leite, DT Lima, AJ Monteiro, JJ Sidrim and MF Rocha. Minimum inhibitory concentrations of amphotericin B, azoles and caspofungin against Candida species are reduced by farnesol. Med. Mycol. 2013; 51, 53-9.

AR Cordeiro, GC Nogueira, RS Brilhante, CE Teixeira, CI Mourao, SD Castelo-Branco, AM Paiva, JF Ribeiro, AJ Monteiro, JJ Sidrim and MF Rocha. Farnesol inhibits in vitro growth of the Cryptococcus neoformans species complex with no significant changes in virulence-related exoenzymes. Vet. Microbiol. 2012; 159, 375-80.

DS Castelo-Branco, GB Riello, DC Vasconcelos, GM Guedes, R Serpa, TJPG Bandeira, AJ Monteiro, RA Cordeiro, MFG Rocha, JJC Sidrim and RSN Brilhante. Farnesol increases the susceptibility of Burkholderia pseudomallei biofilm to antimicrobials used to treat melioidosis. J. Appl. Microbiol. 2016; 120, 600-6.

DR Monteiro, LS Arias, RA Fernandes, LFD Silva, MD Castilho, TO Rosa, APM Vieira, FG Straioto, DB Barbosa and ACB Delbem. Antifungal activity of tyrosol and farnesol used in combination against Candida species in the planktonic state or forming biofilms. J. Appl. Microbiol. 2017; 123, 392-400.

LS Arias, AC Delbem, RA Fernandes, DB Barbosa and DR Monteiro. Activity of tyrosol against single and mixed-species oral biofilms. J. Appl. Microbiol. 2016; 120, 1240-9.

M Martins, M Henriques, J Azeredo, SM Rocha, MA Coimbra and R Oliveira. Morphogenesis control in Candida albicans and Candida dubliniensis through signaling molecules produced by planktonic and biofilm cells. Eukaryot. Cell. 2007; 6, 2429-36.




How to Cite

WONGSUK, T. ., & SUKPHOPETCH, P. . (2019). Effect of Quarum Sensing Molecules on Aspergillus fumigatus . Walailak Journal of Science and Technology (WJST), 17(4), 348–358. https://doi.org/10.48048/wjst.2020.6172