Abstract
The aim of this study was to evaluate the effect of farnesol on the production of acids and hydrolytic enzymes by biofilms of Streptococcus mutans and Candida albicans. The present study also evaluated the time-kill curve and the effect of farnesol on matrix composition and structure of single-species and dual-species biofilms. Farnesol, at subinhibitory concentrations, showed a significant reduction in S. mutans biofilm acid production, but did not alter C. albicans hydrolytic enzyme production. The number of cultivable cells of both microorganisms was significantly reduced after 8 h of contact with farnesol. Extracellular matrix protein content was reduced for biofilms formed in the presence of farnesol. In addition, confocal laser scanning and scanning electron microscopy displayed structural alterations in all biofilms treated with farnesol, which included reduction in viable cells and extracellular matrix. In conclusion, farnesol showed favorable properties controlling some virulence factors of S. mutans and C. albicans biofilms. These findings should stimulate further studies using this quorum-sensing molecule, combined with other drugs, to prevent or treat biofilm-associated oral diseases.
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References
Bowen WH, Madison KM, Pearson SK (1988) Influence of desalivation in rats on incidence of caries in intact cagemates. J Dent Res 67:1316–1318. https://doi.org/10.1177/00220345880670101401
Falsetta ML, Klein MI, Colonne PM, Scott-Anne K, Gregoire S, Pai CH, Gonzalez-Begne M, Watson G, Krysan DJ, Bowen WH, Koo H (2014) Symbiotic relationship between Streptococcus mutans and Candida albicans synergizes virulence of plaque biofilms in vivo. Infect Immun 82:1968–1981. https://doi.org/10.1128/IAI.00087-14
Douglas LJ (2003) Candida biofilms and their role in infection. Trends Microbiol 11:30–36. https://doi.org/10.1016/S0966-842X(02)00002-1
Nobile CJ, Nett JE, Hernday AD, Homann OR, Deneault JS, Nantel A, Andes DR, Johnson AD, Mitchell AP (2009) Biofilm matrix regulation by Candida albicans Zap1. PLoS Biol 7:e1000133. https://doi.org/10.1371/journal.pbio.1000133
Zarnowski R, Westler WM, Lacmbouh GA, Marita JM, Bothe JR, Bernhardt J, Lounes-Hadj Sahraoui A, Fontaine J, Sanchez H, Hatfield RD, Ntambi JM, Nett JE, Mitchell AP, Andes DR (2014) Novel entries in a fungal biofilm matrix encyclopedia. Mbio 5:01333. https://doi.org/10.1128/mBio.01333-14
Schaller M, Borelli C, Korting HC, Hube B (2005) Hydrolytic enzymes as virulence factors of Candida albicans. Mycoses 48:365–377. https://doi.org/10.1111/j.1439-0507.2005.01165.x
Rapala-Kozik M, Bochenska O, Zajac D, Karkowska-Kuleta J, Gogol M, Zawrotniak M, Kozik A (2017) Extracellular proteinases of Candida species pathogenic yeasts. Mol Oral Microbiol. https://doi.org/10.1111/omi.12206
Marcenes W, Kassebaum NJ, Bernabe E, Flaxman A, Naghavi M, Lopez A, Murray CJ (2013) Global burden of oral conditions in 1990–2010: a systematic analysis. J Dent Res 92:592–597. https://doi.org/10.1177/0022034513490168
Raja M, Hannan A, Ali K (2010) Association of oral candidal carriage with dental caries in children. Caries Res 44:272–276. https://doi.org/10.1159/000314675
Peleg AY, Hogan DA, Mylonakis E (2010) Medically important bacterial-fungal interactions. Nat Rev Microbiol 8:340–349. https://doi.org/10.1038/nrmicro2313
Zhang LH, Dong YH (2004) Quorum sensing and signal interference: diverse implications. Mol Microbiol 53:1563–1571. https://doi.org/10.1111/j.1365-2958.2004.04234.x
Pacheco AR, Sperandio V (2009) Inter-kingdom signaling: chemical language between bacteria and host. Curr Opin Microbiol 12:192–198. https://doi.org/10.1016/j.mib.2009.01.006
Koul S, Kalia VC (2017) Multiplicity of quorum quenching enzymes: a potential mechanism to limit quorum sensing bacterial population. Indian J Microbiol 57:100–108. https://doi.org/10.1007/s12088-016-0633-1
Wang H, Tu F, Gui Z, Lu X, Chu W (2013) Antibiotic resistance profiles and quorum sensing-dependent virulence factors in clinical isolates of pseudomonas aeruginosa. Indian J Microbiol 53:163–167. https://doi.org/10.1007/s12088-013-0370-7
Hu M, Zhang C, Mu Y, Shen Q, Feng Y (2010) Indole affects biofilm formation in bacteria. Indian J Microbiol 50:362–368. https://doi.org/10.1007/s12088-011-0142-1
Martins M, Henriques M, Azeredo J, Rocha SM, Coimbra MA, Oliveira R (2007) Morphogenesis control in Candida albicans and Candida dubliniensis through signaling molecules produced by planktonic and biofilm cells. Eukaryot Cell 6:2429–2436. https://doi.org/10.1128/EC.00252-07
Semighini CP, Hornby JM, Dumitru R, Nickerson KW, Harris SD (2006) Farnesol-induced apoptosis in Aspergillus nidulans reveals a possible mechanism for antagonistic interactions between fungi. Mol Microbiol 59:753–764. https://doi.org/10.1111/j.1365-2958.2005.04976.x
Lamfon H, Porter SR, McCullough M, Pratten J (2003) Formation of Candida albicans biofilms on non-shedding oral surfaces. Eur J Oral Sci 111:465–471. https://doi.org/10.1111/j.0909-8836.2003.00084.x
Monteiro DR, Gorup LF, Silva S, Negri M, de Camargo ER, Oliveira R, Barbosa DB, Henriques M (2011) Silver colloidal nanoparticles: antifungal effect against adhered cells and biofilms of Candida albicans and Candida glabrata. Biofouling 27:711–719. https://doi.org/10.1080/08927014.2011.599101
Arias LS, Delbem AC, Fernandes RA, Barbosa DB, Monteiro DR (2016) Activity of tyrosol against single and mixed-species oral biofilms. J Appl Microbiol 120:1240–1249. https://doi.org/10.1111/jam.13070
Alves F, de Oliveira Mima EG, Passador RCP, Bagnato VS, Jorge JH, Pavarina AC (2017) Virulence factors of fluconazole-susceptible and fluconazole-resistant Candida albicans after antimicrobial photodynamic therapy. Lasers Med Sci 32:815–826. https://doi.org/10.1007/s10103-017-2177
Fernandes RA, Monteiro DR, Arias LS, Fernandes GL, Delbem AC, Barbosa DB (2016) Biofilm formation by Candida albicans and Streptococcus mutans in the presence of farnesol: a quantitative evaluation. Biofouling 32:329–338. https://doi.org/10.1080/08927014.2016.1144053
Hasan S, Danishuddin M, Adil M, Singh K, Verma PK, Khan AU (2012) Efficacy of E. officinalis on the cariogenic properties of Streptococcus mutans: a novel and alternative approach to suppress quorum-sensing mechanism. PLoS ONE 7:e40319. https://doi.org/10.1371/journal.pone.0040319
Aoki S, Ito-Kuwa S, Nakamura Y, Masuhara T (1990) Comparative pathogenicity of a wild-type strain and respiratory mutants of Candida albicans in mice. Zentralblatt fur Bakteriologie: Int J Med Microbiol 273:332–343. https://doi.org/10.1016/S0934-8840(11)80437-8
Price MF, Wilkinson ID, Gentry LO (1982) Plate method for detection of phospholipase activity in Candida albicans. Sabouraudia 20:7–14. https://doi.org/10.1080/00362178285380031
Tsang CS, Chu FC, Leung WK, Jin LJ, Samaranayake LP, Siu SC (2007) Phospholipase, proteinase and haemolytic activities of Candida albicans isolated from oral cavities of patients with type 2 diabetes mellitus. J Med Microbiol 56:1393–1398. https://doi.org/10.1099/jmm.0.47303-0
Sacristan B, Blanco MT, Galan-Ladero MA, Blanco J, Perez-Giraldo C, Gomez-Garcia AC (2011) Aspartyl proteinase, phospholipase, hemolytic activities and biofilm production of Candida albicans isolated from bronchial aspirates of ICU patients. Med Mycol 49:94–97. https://doi.org/10.3109/13693786.2010.482947
Williamson MI, Samaranayake LP, MacFarlane TW (1986) Phospholipase activity as a criterion for biotyping Candida albicans. J Med Vet Mycol 24:415–417. https://doi.org/10.1080/02681218680000631
Tong Z, Zhang L, Ling J, Jian Y, Huang L, Deng D (2014) An in vitro study on the effect of free amino acids alone or in combination with nisin on biofilms as well as on planktonic bacteria of Streptococcus mutans. PLoS ONE 9:e99513. https://doi.org/10.1371/journal.pone.0099513
Zhou LN, Yao WF, Liu J, Shang J, Shan MQ, Zhang L, Ding AW (2013) Protective effect of different solvent extracts from platycladi cacumen carbonisatum on LPS-induced human umbilical vein endothelial cells damage. Zhongguo Zhong Yao Za Zhi 38:3933–3938. https://doi.org/10.4268/cjcmm20132227
Dubois MGK, Hamilton JK, Rebers PA, Smith F (1956) Colorimetric method for determination of sugars and related substances. Anal Chem 38:3933–3938. https://doi.org/10.1021/ac60111a017
Klein MI, Hwang G, Santos PH, Campanella OH, Koo H (2015) Streptococcus mutans-derived extracellular matrix in cariogenic oral biofilms. Front Cell Infect Microbiol 13:5–10. https://doi.org/10.3389/fcimb.2015.00010
Paes Leme AF, Koo H, Bellato CM, Bedi G, Cury JA (2006) The role of sucrose in cariogenic dental biofilm formation–new insight. J Dent Res 85:878–887. https://doi.org/10.1177/154405910608501002
Jeon JG, Pandit S, Xiao J, Gregoire S, Falsetta ML, Klein MI, Koo H (2011) Influences of trans-trans farnesol, a membrane-targeting sesquiterpenoid, on Streptococcus mutans physiology and survival within mixed-species oral biofilms. Int J Oral Sci 3:98–106. https://doi.org/10.4248/IJOS11038
Singh BN, Upreti DK, Singh BR, Pandey G, Verma S, Roy S, Naqvi AH, Rawat AK (2015) Quercetin sensitizes fluconazole-resistant candida albicans to induce apoptotic cell death by modulating quorum sensing. Antimicrob Agents Chemother 59:2153–2168. https://doi.org/10.1128/AAC.03599-14
Koo H, Rosalen PL, Cury JA, Park YK, Bowen WH (2002) Effects of compounds found in propolis on Streptococcus mutans growth and on glucosyltransferase activity. Antimicrob Agents Chemother 46:1302–1309. https://doi.org/10.1128/AAC.46.5.1302-1309.2002
de Melo NI, de Carvalho CE, Fracarolli L, Cunha WR, Veneziani RC, Martins CH, Crotti AE (2015) Antimicrobial activity of the essential oil of Tetradenia riparia (Hochst.) Codd. (Lamiaceae) against cariogenic bacteria. Braz J Microbiol 46:519–525. https://doi.org/10.1590/S1517-838246246220140649
Polke M, Leonhardt I, Kurzai O, Jacobsen ID (2017) Farnesol signalling in Candida albicans–more than just communication. Crit Rev Microbiol 44:230–243. https://doi.org/10.1080/1040841X.2017.1337711
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The authors thank George Duchow for the English review of the manuscript. This study was supported by the São Paulo Research Foundation (FAPESP, Grant Number 2013/23592-0), Brazil.
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Fernandes, R.A., Monteiro, D.R., Arias, L.S. et al. Virulence Factors in Candida albicans and Streptococcus mutans Biofilms Mediated by Farnesol. Indian J Microbiol 58, 138–145 (2018). https://doi.org/10.1007/s12088-018-0714-4
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DOI: https://doi.org/10.1007/s12088-018-0714-4