Inhibition of Candida albicans cell growth and biofilm formation by a bioactive extract produced by soil Streptomyces strain GCAL-25


  • Laura E. Córdova-Dávalos Departamento de Microbiología, Centro de Ciencia Básica, Universidad Autónoma de Aguascalientes, Av. Universidad No. 940, Aguascalientes
  • Karla G. Escobedo-Chávez Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, A.C Unidad Sureste, Science and Technology Park Yucatán, Tablaje Catastral 31264 km, 5.5 Carr. Sierra Papacal – Chuburná Puerto, Mérida, Yucatán
  • Zahaed Evangelista-Martínez Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, A.C Unidad Sureste, Science and Technology Park Yucatán, Tablaje Catastral 31264 km, 5.5 Carr. Sierra Papacal – Chuburná Puerto, Mérida, Yucatán


Candida albicans, biofilm, metabolites, antifungal, Streptomyces


Resistance to antifungal agents is a major public health concern since multidrug resistant (MDR) strains of Candida albicans have caused severe infections among immunosuppressed, diabetic and other hospital patients. This study focused on evaluating the effects of a bioactive extract (BEx) produced by a novel Streptomyces species on C. albicans cell germination and biofilm formation. Agar disk diffusion assays were used to select a streptomycete with inhibitory activity over C. albicans cells. Thereafter, minimal inhibition concentration (MIC) and time-kill values were obtained for the BEx prepared from the isolate GCAL-25. Also, the effects of BEx on biofilm formation were analyzed. Results showed that the GCAL-25 isolate from the Streptomyces genus displayed inhibitory activity on C. albicans. A paper disk soaked with BEx showed an inhibitory halo around confluent growing cells of C. albicans. The calculated MIC values for BEx indicated that C. albicans was three times more susceptible to BEx than the control fungicide, amphotericin B (AmpB). Time-kill studies with ½x and 1xMIC of BEx showed severe negative effects on cell viability, suggesting a strong fungicidal activity. In addition, an important reduction of C. albicans biofilm formation was observed. The BEx from Streptomyces sp. GCAL-25 altered yeast-to-hyphae transitions and induced abnormal cell morphology (e.g. cell shrinkage), including impairments of cell membrane integrity with negative effects on biofilm formation.

Received: September 8, 2017; Revised: November 29, 2017; Accepted: December 7, 2017; Published online: December 29, 2017

How to cite this article: Córdova-Dávalos LE, Escobedo-Chávez KG, Evangelista-Martínez Z. Inhibition of Candida albicans cell growth and biofilm formation by a bioactive extract produced by soil Streptomyces strain GCAL-25. Arch Biol Sci. 2018;70(2):387-96.


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François L, Mayer DW, Bernhard H. Candida albicans pathogenicity mechanisms. Virulence. 2013;4(2):119-28.

Centers for Disease Control and Prevention (US). Antibiotic Resistance Threats in the United States, 2013: Fluconazole-Resistant Candida. U.S Department of Health and Human Services. [updated 2017 Jun 22; cited 2017 Dec 20]. Available from:

Ding X, Yan D, Sun W, Zeng Z. Epidemiology and risk factors for nosocomial Non-Candida albicans candidemia in adult patients at a tertiary care hospital in North China. Med Mycol. 2015;53(7):684-90.

Gaona-Flores VA, Campos-Navarro LA, Cervantes-Tovar RM. The epidemiology of fungemia in an infectious diseases hospital in Mexico City: A 10-year retrospective review. Med Mycol. 2016;54(6):600-4.

Sanguinetti M, Posteraro B, Lass-Flörl C. Antifungal drug resistance among Candida species: mechanisms and clinical impact. Mycoses. 2015;58(S2):2-13.

Nobile CJ, Johnson AD. Candida albicans biofilms and human disease. Annu Rev Microbiol. 2015;69:71-92.

Kojic EM, Darouiche RO. Candida infections of medical devices. Clin Microbiol Rev. 2004;17(2):255-67.

Ramage G, Saville SP, Thomas DP, López-Ribot JL. Candida biofilms: an update. Eucaryot Cell. 2005;4(4):633-8.

Taff HT, Mitchell KF, Edward JA, Andes DR. Mechanisms of Candida biofilm drug resistance. Future Microbiol. 2013;8(10):1325-37.

Sanglard D, Coste AT. Activity of isavuconazole and other azoles against Candida clinical isolates and yeast model systems with known azole resistance mechanisms. Antimicrob Agents Chemother. 2015;60(1):229-38.

Martel CM, Parker JE, Bader O, Weig M. Identification and characterization of four azole-resistant erg3 mutants of Candida albicans. Antimicrob Agents Chemother. 2010;54(11):4527-33.

Donadio S, Sosio M, Lancini G. Impact of the first Streptomyces genome sequence on the discovery and production of bioactive substances. Appl Microbiol Biotechnol. 2002;60(4):377-80.

Brautaset T, Sletta H, Nedal A, Borgos SEF. Improved antifungal polyene macrolides via engineering of the nystatin biosynthetic genes in Streptomyces noursei. Chem Biol. 2008;15(11):1198–206.

Caffrey P, Lynch S, Flood E. Finnan S. Amphotericin biosynthesis in Streptomyces nodosus: deductions from analysis of polyketide synthase and late genes. Chem Biol. 2001;8(7):713-23.

Kim DG, Moon K, Kim SH, Park SH. Bahamaolides A and B, antifungal polyene polyol macrolides from the marine actinomycete Streptomyces sp. J Nat Prod. 2012;75(5):959-67.

Oh DC, Scott JJ, Currie CR, Clardy J. Mycangimycin, a polyene peroxide from a mutualist Streptomyces sp. Organic Lett. 2009;11(3):633-36.

Sheperd MD, Kharel MK, Bosserman MA, Rohr J. Laboratory Maintenance of Streptomyces species. In: Cowen LE, Grigg M, McBride A, Payne SM, Stevenson B, editors. Current Protocols in Microbiology. Kentucky, US: John Wiley & Sons, Inc; 2010. p. 18:E:10E.1:10E.1.1–10E.1.8.

Evangelista-Martínez Z. Isolation and characterization of soil Streptomyces species as a potential biological control agent against fungal plant pathogens. W J Microbiol Biotech. 2014;30(5):1639-47.

Shirling EB, Gottlieb D. Methods for characterization of Streptomyces species. Int J Syst Bacteriol. 1966;16(3):313–40.

Weisburg WG, Barns SM, Pelletier DA, Lane DJ. 16S ribosomal DNA amplification for phylogenetic study. J Bacteriol. 1991;173(2):697-703.

Altschul SF, Madden TL, Schaumlffer AA, Zhang J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997;25(17):3389-402.

National Committee for Clinical Laboratory Standards. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard. Second edition, NCCLS document M27-A2. Wayne, PA (US): National Committee for Clinical Laboratory Standards; 2002.

Jin Y, Yip HK, Samaranayake YH, Yau JY. Biofilm-forming ability of Candida albicans is unlikely to contribute to high levels of oral yeast carriage in cases of human immunodeficiency virus infection. J Clin Microbiol. 2003;41(7):2961-7.

Li Q, Chen X, Jiang Y, Jiang C. Morphological Identification of Actinobacteria. In Dhanasekaran D, Jiang Y, editors. Actinobacteria - Basics and Biotechnological Applications. Rijeka, Croatia: InTech; 2016. p. 59-86.

Davidson RN, den Boer M, Ritmeijer K. Paromomycin. Trans R Soc Trop Med Hyg. 2009;103(7):653-60.

Petković H, Lukežič T, Šušković J. Biosynthesis of oxytetracycline by Streptomyces rimosus: past, present and future directions in the development of tetracycline antibiotics. Food Technol Biotechnol. 2017;55(1):1-27.

Yuan WM, Crawford DL. Characterization of Streptomyces lydicus WYEC108 as a potential biocontrol agent against fungal root and seed rots. Appl Environ Microbiol. 1995;61(8):3119-28.

Ahmad KF, Minion J, Al-Motairi A, Benedetti A. An updated systematic review and meta-analysis on the treatment of active tuberculosis in patients with HIV infection. Clin Infect Dis. 2012;55(8):1154-63.

Kim J, Sudbery P. Candida albicans, a major human fungal pathogen. J Microbiol. 2011;49(2):171-7.

Chudzik B, Koselski M, Czuryło A, Trębacz K. A new look at the antibiotic amphotericin B effect on Candida albicans plasma membrane permeability and cell viability functions. Eur Biophys J. 2015;44(1-2):77-90.

Sudbery PE. Growth of Candida albicans hyphae. Nat Rev Microbiol. 2011;9(10):737-48.

Cleary IA, Reinhard SM, Lazzell AL, Monteagudo C. Examination of the pathogenic potential of Candida albicans filamentous cells in an animal model of haematogenously disseminated candidiasis. FEMS Yeast Res. 2016;16(2):fow011.

Lu Y, Su C, Liu H. Candida albicans hyphal initiation and elongation. Trends Microbiol. 2014;22(12):707-14.

Pu Y, Liu A, Zheng Y, Ye B. In vitro damage of Candida albicans biofilms by chitosan. Exp Ther Med. 2014;8(3):929-34.

Kagan S, Jabbour A, Sionov E, Alquntar AA. Anti-Candida albicans biofilm effect of novel heterocyclic compounds. J Antimicrob Chemother. 2014;69(2):416-27.

Haque F, Alfatah N, Ganesan K, Bhattacharyya MS. Inhibitory effect of sophorolipid on Candida albicans biofilm formation and hyphal growth. Sci Rep. 2016;6:23575.

Kumar V, Naik B, Gusain O, Bisht GS. An actinomycete isolate from solitary wasp mud nest having strong antibacterial activity and kills the Candida cells due to the shrinkage and the cytosolic loss. Front Microbiol. 2014;5:446.

Srivastava V, Dubey AK. Anti-biofilm activity of the metabolites of Streptomyces chrestomyceticus strain ADP4 against Candida albicans. J Biosci Bioeng. 2016;122(4):434-40.

Chandra J, Kuhn DM, Mukherjee PK, Hoyer LL, McCormick T, Ghannoum MA. Biofilm formation by the fungal pathogen Candida albicans: Development, architecture, and drug resistance. J Bact. 2001;183(18):5385-94.

Finkel JS, Mitchell AP. Genetic control of Candida albicans biofilm development. Nat Rev Microbiol. 2011;9(2):109-18.




How to Cite

Córdova-Dávalos LE, Escobedo-Chávez KG, Evangelista-Martínez Z. Inhibition of Candida albicans cell growth and biofilm formation by a bioactive extract produced by soil Streptomyces strain GCAL-25. Arch Biol Sci [Internet]. 2018May30 [cited 2024Jul.20];70(2):387-96. Available from: