Oral Dysbiosis Exacerbates Candida parapsilosis Sensu Stricto Biofilm Production via Up-Regulation of the CPH2 Biofilm Master Gene


Introduction: Candida parapsilosis sensu stricto is the second to third most frequent cause of candidemia. Studies place this yeast as a frequent colonizer of niches of the oral cavity, predominantly in pathological conditions. We hypothesize that a buccal environment in dysbiosis enhances the virulence of C. parapsilosis sensu stricto.
Objective: To evaluate the phenotype and molecular level of the production of biofilm in oral isolates of Candida parapsilosis sensu stricto and correlate the results with the clinical origin (dysbiosis versus eubiosis).
Materials and Methods: The biofilm-forming ability was compared in 50 oral isolates of Candida parapsilosis sensu stricto obtained from patients with and without oral dysbiosis; by quantification of metabolic activity. The results were corroborated by confocal fluorescence microscopy, and correlated with the transcriptional activity of CPH2, by RT-qPCR. The data were analysed by Excel 2010, and InfoStat 2018, with a 95% confidence interval.
Results: The metabolic activity in biofilm was significantly higher in oral dysbiosis relative to control (p = 0.0025). Basal expression of CPH2 increased 2.8 times more in oral dysbiosis related to the control condition and showed no significant differences with pathogenic isolates of this same yeast, derived from onychomycosis lesions.
Conclusion: The oral cavity in dysbiosis increases the virulence of C. parapsilosis sensu stricto due to possible changes in epigenetic marks. This finding suggests that the oral cavity in dysbiosis may be an alternative route to the skin in the epidemiology of nosocomial candidemia.


Candida parapsilosis sensu stricto, virulence, oral dysbiosis, oral eubiosis, CPH2 gene master

Get access to the full version of this article.

Article Info

Article Type
Research Article
Publication history
Received: Sat 13, Mar 2021
Accepted: Thu 25, Mar 2021
Published: Thu 22, Apr 2021
© 2021 Rodríguez ML. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Hosting by Science Repository. All rights reserved.
DOI: 10.31487/j.DOBCR.2021.01.07

Author Info

Corresponding Author
Rodríguez ML
Semiology and Diagnostic Clinic, School of Dentistry, University of Cuenca-Ecuador, Cuenca, Ecuador

Figures & Tables

Get access to the full version of this article.


1.     Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP et al. (2004) Nosocomial blood-stream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39: 309-317. [Crossref]

2.     Pfaller MA, Moet GJ, Messer SA, Jones RN, Castanheira M (2011) Candida bloodstream infections: comparison of species distributions and antifun- gal resistance patterns in community-onset and nosocomial isolates in the SENTRY Antimicrobial Surveillance Program, 2008-2009. Antimicrob Agents Chemother 55: 561-566. [Crossref]

3.     Tóth R, Nosek J, Mora Montes HM, Gabaldon T, Bliss JM et al. (2019) Candida parapsilosis: from genes to the bedside. Clin Microbiol Rev 32: e00111-e00118. [Crossref]

4.     Quindos G (2014) Epidemiology of candidaemia and invasive candidi-asis. A changing face. Revista Iberoamericana de Micología 31: 42-48. [Crossref]

5.     Guinea J (2014) Global trends in the distribution of Candida species causing candidemia. Clin Microbiol Infect 20: 5-10. [Crossref]

6.     Arsic V, Otasevic S, Janic D, Minić P, Matijašević J et al. (2018) Candida bloodstream infections in Serbia: first multicentre report of a national prospective observational survey in intensive care units. Mycoses 61: 70-78. [Crossref]

7.     Lockhart SR, Iqbal N, Cleveland AA, Farley MM, Harrison LH et al. (2012) Species identification and antifungal susceptibility testing of Candida blood- stream isolates from population-based surveillance studies in two U.S. cities from 2008 to 2011. J Clin Microbiol 50: 3435-3442. [Crossref]

8.     Conde Rosa A, Amador R, Perez Torres D, Colon E, Sanchez Rivera C et al. (2010) Candidemia distribution, associated risk factors, and attributed mortality at a university-based medical center. Puerto Rico Health Sci J 29: 26-29. [Crossref]

9.     da Matta D, Remondi A, Lopez Colombo A (2017) Revisiting Species Distribution and Antifungal Susceptibility of Candida Bloodstream Isolates from Latin American Medical Centers. J Fungi (Basel) 3: 24. [Crossref]

10.  Kleinegger CL, Lockhart SR, Vargas K, Soll DR (1996) Frequency, intensity, species, and strains of oral Candida vary as a function of host age. J Clin Microbiol 34: 2246-2254. [Crossref]

11.  Ghannoum MA, Jurevic RJ, Mukherjee PK, Cui F, Sikaroodi M et al. (2010) Characterization of the Oral Fungal Microbiome (Mycobiome) in Healthy Individuals. PLoS Pathogen 6: e1000713. [Crossref]

12.  Yang Y, Leaw S, Wang A, Chen HT, Cheng WT et al. (2011) Characterization of yeasts colonizing in healthy individuals. Med Mycol 49: 103-106. [Crossref]

13.  Peters B, Wu J, Hayes R, Ahn J (2017) The oral fungal mycobiome: characteristics and relation to periodontitis in a pilot study. BMC Microbiol 17: 157. [Crossref]

14.  Rodríguez L, Jewtuchowicz V (2016) Molecular characterization of Candida parapsilosis species complex in niches of the oral cavity in a cohort of patients from Argentina with different oral and dental clinical manifestations. J Dent Sci Ther 1: 18-25.

15.  Rodríguez L, Nastri L, Jewtuchowicz V (2018) The Oral Cavity: A reservoir that favors colonization and selection of Candida parapsilosis sensu stricto strains with high pathogen potential under conditions of gingival-periodontal disease. J Dent Sci Ther 2: 1-9.

16.  Rubio N, Puia S, Toranzo S, Brusca MI (2015) Fungal invasion of connective tissue in patienst with gingival-periodontal disease. Rev Iberoam Micol 32: 20-24. [Crossref]

17.  Jewtuchowicz VM, Mujica MT, Brusca MI, Sordelli N, Malzone MC et al. (2008) Phenotypic and genotypic identification of Candida dubliniensis from subgingival sites in immunocompetent subjects in Argentina. Oral Microbiol Immunol 23: 505-509. [Crossref]

18.  Canabarro A, Valle C, Farias MR, Santos FB, Lazera M et al. (2013) Association of subgingival colonization of Candida albicans and other yeasts with severity of chronic periodontitis. J Periodontal Res 48: 428-432. [Crossref]

19.  Alrabiah M, Alshagroud R, Alsahhaf A, Almojaly SA, Abduljabbar T et al. (2019) Presence of Candida species in the subgingival oral biofilm of patients with peri-implantitis. Clin Implant Dent Relat Res 21: 781-785. [Crossref]

20.  Fanello S, Bouchara JP, Sauteron M, Delbos V, Parot E (2006) Predictive value of oral colonization by Candida yeasts for the onset of a nosocomial infection in elderly hospitalized patients. J Med Microbiol 55: 223-228. [Crossref]

21.  Holland LM, Schröder MS, Turner SA, Taff H, Andes D et al. (2014) Comparative phenotypic analysis of the major fungal pathogens Candida parapsilosis and Candida albicans. PLoS Pathog 10: e1004365. [Crossref]

22.  Armitage GC (1999) Development of a classification system for periodontal diseases and conditions. Ann Periodontol 4: 1-6. [Crossref]

23.  Hamzah H, Hertiani T, Tunjung S, Murti Y, Nuryastuti T (2020) The Inhibition and Degradation Activity of Demethoxycurcumin as Antibiofilm on C. albicans ATCC 10231. Res J Pharm Tech 13: 377-382.

24.  Durán EL, Mujica MT, Jewtuchowicz VM, Finquelievich JL, Pinoni MV et al. (2007) Examination of the genetic variability among biofilm-forming Candida albicans clinical isolates. Rev Iberoam Micol 4: 268-271. [Crossref]

25.  Peeters E, Nelis HJ, Coenye T (2008) Comparison of multiple methods for quantification of microbial biofilms grown in microtiter plates. J Microbiol Methods 72: 157-165. [Crossref]

26.  Treviño Rangel RJ, Rodríguez Sánchez IP, Rosas Taraco AG, Hernández Belloa R, González JG et al. (2015) Biofilm formation and genetic variability of BCR1 gene in the Candida parapsilosis complex. Revista Iberoamericana de Micología 32: 180-184. [Crossref]

27.  Sánchez Vargas LO, Estrada Barraza D, Pozos Guillén AJ, Rivas Cáceres R (2013) Biofilm formation by oral clinical isolates of Candida species. Arch Oral Biol 58: 1318-1326. [Crossref]

28.  Gerda R, Lamers G, van de Laar N, Dijkhuizen M, Lagendijk E et al. (2010) Biofilms on tracheoesophageal voice prostheses: a confocal laser scanning microscopy demonstration of mixed bacterial and yeast biofilms. Biofouling 26: 519-526. [Crossref]

29.  Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J et al. (2009) The MIQE Guidelines: Minimum Information for Publication of Quantitative Real-Time PCR Experiments. Clin Chemest 55: 611-622. [Crossref]

30.  Consorcio “American Type Culture Collection” (ATCC): Strain Candida parapsilosis sensu tricto ATCC® 22019TM.

31.  Rodríguez Ml, Alcaraz ES, Rosa AC, Jewtuchowicz VM (2020) The oral cavity promotes virulence of Candida parapsilosis sensu stricto via up- regulation of BCR1. World J Adv Res Rev 6: 120-133.

32.  Shafeeq S, Pannanusorn S, Elsharabasy Y, Ramírez Zavala B, Morschhäuser J et al. (2019) Impact of manganese on biofilm formation and cell morphology of Candida parapsilosis clinical isolates with different biofilm forming abilities. FEMS Yeast Res 19: foz057. [Crossref]

33.  Kinane DF, Stathopoulou PG, Papapanou PN (2017) Periodontal disease. Nat Rev Dis Primers 3: 17038. [Crossref]

34.  Michaud D, Fu Z, Shi J, Chung M (2017) Periodontal disease, Tooth Loss, and Cancer Risk. Epidemiol Rev 39: 49-58. [Crossref]

35.  Tomás I, Camelo A, Balsa C, Castellano A, Novoa L et al. (2016) Nuevo modelo de patogenia de la periodontitis crónica: de la enfermedad infecciosa a la disbiosis polimicrobiana. RCOE 21: 131-145.

36.  Bullon P, Morillo JM, Ramirez Tortosa MC, Quiles JL, Newman HN et al. (2009) Metabolic syndrome and periodontitis: is oxidative stress a common link? J Dent Res 88: 503-518. [Crossref]

37.  D'Aiuto F, Nibali L, Parkar M, Patel K, Suvan J et al. (2010) Oxidative stress, systemic inflammation, and severe periodontitis. J Dent Res 89: 1241-1246. [Crossref]

38.  de Barros P, Rossoni RD, De Camargo Ribeiro F, Campos Junqueira J, Cardoso Jorge AO (2017) Temporal Profile of Biofilm Formation, Gene Expression and Virulence Analysis in Candida albicans Strains. Mycopathologia 182: 285-295. [Crossref]

39.  Garbacz K, Jarzembowski T, Kwapisz E, Daca A, Witkowski J (2018) Do the oral Staphylococcus aureus strains from denture wearers have a greater pathogenicity potential? J Oral Microbiol 11: 1536193. [Crossref]

40.  Bartnicka D, Karkowska Kuleta J, Zawrotniak M, Satała D, Michalik K et al. (2019) Adhesive protein-mediated crosstalk between Candida albicans and Porphyromonas gingivalis in dual species biofilm protects the anerobic bacterium unfavorable oxic enviroment. Sci Rep 9: 4376. [Crossref]

41.  Sztukowska M, Dutton L, Delaney C, Ramsdale M, Ramage G et al. (2018) Community Development between Porphyromonas gingivalis and Candida albicans Mediated by InlJ and Als3. mBio 9: e00202- e00218. [Crossref]