Infecções por Candida na cavidade oral e orofaringe: resistência aos medicamentos, virulência e a busca por alternativas naturais.
Palavras-chave:
Candida spp., Candidíase orofaríngea, Resistência a medicamentos, Fatores de virulência, Produtos naturaisResumo
Espécies de Candida são responsáveis por uma proporção significativa de infecções fúngicas em humanos, principalmente relacionadas a infecções oportunistas em indivíduos imunocomprometidos. Dentre as espécies patogênicas mais relevantes à saúde humana estão Candida albicans, Candida glabrata (Nakaseomyces glabrata), Candida auris, Candida tropicalis e Candida krusei (Pichia kudriavzevii), todas encontradas na lista de patógenos prioritários fúngicos (FPPL) recentemente divulgada pela Organização Mundial da Saúde (OMS). Embora C. albicans permaneça como o agente causador predominante, observa-se um aumento na incidência de espécies Candida não-albicans (NCAC), particularmente Candida glabrata. As espécies NCAC frequentemente exibem resistência a medicamentos antifúngicos convencionais, representando um desafio terapêutico significativo. Esta revisão examina as principais espécies de Candida associadas à candidíase orofaríngea e seus mecanismos de resistência e virulência. Além disso, avalia a eficácia dos tratamentos atuais e os fatores que contribuem para suas falhas, discutindo perspectivas para novas abordagens terapêuticas, com ênfase no tratamento a partir de produtos naturais.
Downloads
Referências
AHMED, N. et al. COVID-19-Associated Candidiasis: Possible Patho-Mechanism, Predisposing Factors, and Prevention Strategies. Current Microbiology, v. 79, n. 5, p. 1–15, 1 maio 2022.
ARMSTRONG-JAMES, D. et al. Immunotherapeutic approaches to treatment of fungal diseases. The Lancet Infectious Diseases, v. 17, n. 12, p. e393–e402, dez. 2017.
AISY, D. U. et al. The Antifungal Activities of Syzygium aromaticum and Alpinia purpurata Extracts Against Candida krusei: Bioactivity Tests, Molecular Modeling, and Toxicity Tests. Asian Pacific Journal of Cancer Prevention, v. 24, n. 10, p. 3403–3409, 1 out. 2023.
AMBE, N. F. et al. The prevalence, risk factors and antifungal sensitivity pattern of oral candidiasis in HIV/AIDS patients in Kumba District Hospital, South West Region, Cameroon. Pan African Medical Journal, v. 36, n. 1, 19 maio 2020.
ARAIZA, J. et al. Candidiasis oral mixta en pacientes con diabetes de tipo 2: identificación y espectro de sensibilidad. Biomédica, v. 43, n. Sp. 1, p. 97–108, 31 ago. 2023.
ARASTEHFAR, A. et al. COVID-19-Associated Candidiasis (CAC): An Underestimated Complication in the Absence of Immunological Predispositions? Journal of Fungi 2020, Vol. 6, Page 211, v. 6, n. 4, p. 211, 8 out. 2020.
ASKARI, F.; KAUR, R. Candida glabrata : A Tale of Stealth and Endurance. ACS Infectious Diseases, v. 11, n. 1, p. 4–20, 10 jan. 2025.
BATIHA, G. E.-S. et al. The Pharmacological Activity, Biochemical Properties, and Pharmacokinetics of the Major Natural Polyphenolic Flavonoid: Quercetin. Foods, v. 9, n. 3, p. 374, 23 mar. 2020.
BEARDSLEY, J. et al. Candida glabrata (Nakaseomyces glabrata): A systematic review of clinical and microbiological data from 2011 to 2021 to inform the World Health Organization Fungal Priority Pathogens List. Medical Mycology, v. 62, n. 6, 27 jun. 2024.
BERMAN, J.; KRYSAN, D. J. Drug resistance and tolerance in fungi. Nature Reviews Microbiology, v. 18, 11 fev. 2020.
BHATTACHARYA, S.; SAE-TIA, S.; FRIES, B. C. Candidiasis and mechanisms of antifungal resistance. Antibiotics, v. 9, n. 6, p. 1–19, 1 jun. 2020.
BOHNER, F.; PAPP, C.; GÁCSER, A. The effect of antifungal resistance development on the virulence of Candida species. FEMS Yeast Research, v. 22, n. 1, 2022.
BONGOMIN, F. et al. Global and Multi-National Prevalence of Fungal Diseases—Estimate Precision. Journal of Fungi, v. 3, n. 4, p. 57, 1 dez. 2017.
CAMPOS, L. M. et al. Antifungal Annona muricata L. (soursop) extract targets the cell envelope of multi-drug resistant Candida albicans. Journal of Ethnopharmacology, v. 301, 30 jan. 2023.
CHOI, M. J. et al. Resistance Mechanisms and Clinical Features of Fluconazole-Nonsusceptible Candida tropicalis Isolates Compared with Fluconazole-Less-Susceptible Isolates. Antimicrobial Agents and Chemotherapy, v. 60, n. 6, p. 3653–3661, jun. 2016.
CHONG, P. et al. Transcriptomic and Genomic Approaches for Unravelling Candida albicans Biofilm Formation and Drug Resistance—An Update. Genes, v. 9, n. 11, p. 540, 7 nov. 2018.
CZAJKA, K. et al. Molecular Mechanisms Associated with Antifungal Resistance in Pathogenic Candida Species. Cells, v. 12, n. 22, p. 2655–2655, 19 nov. 2023.
HARRISON, B. D. et al. A Tetraploid Intermediate Precedes Aneuploid Formation in Yeasts Exposed to Fluconazole. PLoS Biology, v. 12, n. 3, p. e1001815, 18 mar. 2014.
DA SILVA-ROCHA, W. P. et al. Candida species distribution, genotyping and virulence factors of Candida albicans isolated from the oral cavity of kidney transplant recipients of two geographic regions of Brazil. BMC Oral Health, v. 14, n. 1, p. 20, 15 dez. 2014.
DANTAS-MEDEIROS, R. et al. Antifungal and Antibiofilm Activities of B-Type Oligomeric Procyanidins From Commiphora leptophloeos Used Alone or in Combination With Fluconazole Against Candida spp. Frontiers in Microbiology, v. 12, 22 fev. 2021.
DE CAMPOS RASTEIRO, V. M. et al. Essential oil of Melaleuca alternifolia for the treatment of oral candidiasis induced in an immunosuppressed mouse model. BMC Complementary and Alternative Medicine, v. 14, n. 1, p. 489, 15 dez. 2014.
DE TOLEDO, L. G. et al. Profiling the Cymbopogon nardus Ethanol Extract and Its Antifungal Potential against Candida Species with Different Patterns of Resistance. Journal of the Brazilian Chemical Society, v. 31, n. 9, p. 1926–1938, 1 set. 2020.
DENNING, D. W. Antifungal drug resistance: an update. European Journal of Hospital Pharmacy, v. 29, n. 2, p. 109, 1 mar. 2022.
DESAI, J. V. Candida albicans Hyphae: From Growth Initiation to Invasion. Journal of Fungi 2018, Vol. 4, Page 10, v. 4, n. 1, p. 10, 11 jan. 2018.
DOS SANTOS, M. M.; ISHIDA, K. We need to talk about Candida tropicalis : Virulence factors and survival mechanisms. Medical Mycology, v. 61, n. 8, 2 ago. 2023.
DUGGAL, R. et al. Prevalence of Species-Specific Candidiasis and Status of Oral Hygiene and Dentition among Diabetic Patients. Indian Journal of Dental Research, v. 32, n. 3, p. 292–298, jul. 2021.
DUTTA, A.; BARKER, C.; KALLARAKAL, A. The HIV Treatment Gap: Estimates of the Financial Resources Needed versus Available for Scale-Up of Antiretroviral Therapy in 97 Countries from 2015 to 2020. PLoS Medicine, v. 12, n. 11, 1 nov. 2015.
ELANSARY, Hosam O. et al. Effective antioxidant, antimicrobial and anticancer activities of essential oils of horticultural aromatic crops in northern Egypt. BMC Complementary and Alternative Medicine, v. 18, n. 1, 13 jul. 2018.
EL-SAKHAWY, M. A. et al. Appraisal and characterization of candida load isolated from the oral cavity of smokers. Saudi Journal of Biological Sciences, v. 30, n. 6, p. 103657, jun. 2023.
FERREIRA, R. L. P. S. et al. Mechanisms of action of Lactobacillus spp. in the treatment of oral candidiasis. Brazilian Journal of Biology, v. 84, p. e282609, 20 set. 2024.
FLANAGAN, P. R. et al. The Candida albicans TOR-Activating GTPases Gtr1 and Rhb1 Coregulate Starvation Responses and Biofilm Formation. mSphere, v. 2, n. 6, 27 dez. 2017.
FLOWERS, S. A. et al. Contribution of Clinically Derived Mutations in ERG11 to Azole Resistance in Candida albicans. Antimicrobial Agents and Chemotherapy, v. 59, n. 1, p. 450–460, jan. 2015.
GIL, F. et al. Extracts from Argentinian native plants reverse fluconazole resistance in Candida species by inhibiting the efflux transporters Mdr1 and Cdr1. BMC Complementary Medicine and Therapies, v. 22, n. 1, p. 264, 12 out. 2022.
GÓMEZ-GAVIRIA, M.; MORA-MONTES, H. M. Current Aspects in the Biology, Pathogeny, and Treatment of Candida krusei, a Neglected Fungal Pathogen. Infection and Drug Resistance, v. 13, p. 1673–1689, jun. 2020.
GÓMEZ-GAVIRIA, M.; RAMÍREZ-SOTELO, U.; MORA-MONTES, H. M. Non-albicans Candida Species: Immune Response, Evasion Mechanisms, and New Plant-Derived Alternative Therapies. Journal of Fungi, v. 9, n. 1, p. 11, 21 dez. 2022.
GOULART, L. S. et al. Oral colonization by Candida species in HIV-positive patients: association and antifungal susceptibility study. Einstein (Sao Paulo, Brazil), v. 16, n. 3, p. eAO4224, 6 ago. 2018.
HASSAN, Y.; CHEW, S. Y.; THAN, L. T. L. Candida glabrata: Pathogenicity and Resistance Mechanisms for Adaptation and Survival. Journal of Fungi, v. 7, n. 8, p. 667, 17 ago. 2021.
HELLSTEIN, J. W.; MAREK, C. L. Candidiasis: Red and White Manifestations in the Oral Cavity. Head and Neck Pathology, v. 13, n. 1, p. 25–32, 15 mar. 2019.
JAHANSHIRI, Z.; MANIFAR, S.; HATAMI, F. Evaluation of virulence factors and azole resistance mechanisms of Candida tropicalis isolates from head and neck cancer patients with OPC. Iranian Journal of Microbiology, 13 fev. 2023.
JAMIU, A. T. et al. Update on Candida krusei, a potential multidrug-resistant pathogen. Medical Mycology, v. 59, n. 1, p. 14–30, 4 jan. 2021.
KAPLAN, Y. C. et al. Fluconazole use during breastfeeding. Canadian Family Physician, v. 61, n. 10, p. 875, out. 2015.
KAUR, J.; NOBILE, C. J. Antifungal drug-resistance mechanisms in Candida biofilms. Current Opinion in Microbiology, v. 71, p. 102237, fev. 2023.
KARPIŃSKI, T. M. et al. Anti-Candida and Antibiofilm Activity of Selected Lamiaceae Essential Oils. Frontiers in Bioscience-Landmark, v. 28, n. 2, 16 fev. 2023.
KATSIPOULAKI, M. et al. Candida albicans and Candida glabrata: global priority pathogens. Microbiology and Molecular Biology Reviews, v. 88, n. 2, 27 jun. 2024.
KEIGHLEY, C. et al. Candida tropicalis —A systematic review to inform the World Health Organization of a fungal priority pathogens list. Medical Mycology, v. 62, n. 6, 27 jun. 2024.
KRONEN, R. et al. Creation and Assessment of a Clinical Predictive Calculator and Mortality Associated With Candida krusei Bloodstream Infections. Open Forum Infectious Diseases, v. 5, n. 2, 1 fev. 2018.
KUMAR, P. The influence of Azadirachta indica, Melaleuca alternifolia, and Cocos nucifera on Candida albicans strain in tissue conditioner at varying time intervals. The Journal of Indian Prosthodontic Society, v. 20, n. 2, p. 171, 2020.
LAGMAN, R. et al. Single-Dose Fluconazole Therapy for Oral Thrush in Hospice and Palliative Medicine Patients. American Journal of Hospice and Palliative Medicine®, v. 34, n. 7, p. 645–649, 4 maio 2016.
LALLA, R. V.; PATTON, L. L.; DONGARI-BAGTZOGLOU, A. Oral candidiasis: pathogenesis, clinical presentation, diagnosis and treatment strategies. Journal of the California Dental Association, 2013.
LASS-FLÖRL, C.; STEIXNER, S. The changing epidemiology of fungal infections. Molecular Aspects of Medicine, v. 94, p. 101215, 1 dez. 2023.
LEE, Y. et al. Antifungal Drug Resistance: Molecular Mechanisms in Candida albicans and Beyond. Chemical Reviews, v. 121, n. 6, 22 maio 2020.
LEMOS, A. S. O. et al. Antifungal Activity of the Natural Coumarin Scopoletin Against Planktonic Cells and Biofilms From a Multidrug-Resistant Candida tropicalis Strain. Frontiers in Microbiology, v. 11, 7 jul. 2020.
LEWIS, M. A. O.; WILLIAMS, D. W. Diagnosis and management of oral candidosis. British Dental Journal, v. 223, n. 9, p. 675–681, nov. 2017.
LOCKHART, S. R. et al. Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses. Clinical Infectious Diseases, v. 64, n. 2, p. 134–140, 20 out. 2016.
LOMBARDI, A.; OUANOUNOU, A. Fungal infections in dentistry: Clinical presentations, diagnosis, and treatment alternatives. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, v. 130, n. 5, p. 533–546, nov. 2020.
LOPES, J. P.; LIONAKIS, M. S. Pathogenesis and virulence of Candida albicans. Virulence, Taylor and Francis Ltd.,, 2022.
LÓPEZ-MARMOLEJO, A. L. et al. Microevolution of Candida glabrata (Nakaseomyces glabrata) during an infection. Fungal Genetics and Biology, v. 172, p. 103891, jun. 2024.
LU, Y.; SU, C.; LIU, H. Candida albicans hyphal initiation and elongation. Trends in Microbiology, v. 22, n. 12, p. 707–714, 1 dez. 2014.
LYU, X. et al. Efficacy of nystatin for the treatment of oral candidiasis: a systematic review and meta-analysis. Drug Design, Development and Therapy, v. 10, p. 1161, mar. 2016.
MAHESHWARI, M.; KAUR, R.; CHADHA, S. Candida Species Prevalence Profile in HIV Seropositive Patients from a Major Tertiary Care Hospital in New Delhi, India. Journal of Pathogens, v. 2016, p. 6204804, 2016.
MANDRAS, Narcisa et al. The Inhibition of Non-albicans Candida Species and Uncommon Yeast Pathogens by Selected Essential Oils and Their Major Compounds. Molecules, Vol. 26, Page 4937, v. 26, n. 16, p. 4937, 15 ago. 2021.
MARTINEZ, R. F. F. et al. Oral Candida spp carriers: its prevalence in patients with type 2 Diabetes Mellitus. Anais Brasileiros de Dermatologia, v. 88, n. 2, p. 222–225, 2013.
MARTÍNEZ-HERRERA, E. et al. Antifungal Resistance in Clinical Isolates of Candida glabrata in Ibero-America. Journal of Fungi, v. 8, n. 1, p. 14, 1 jan. 2021.
MEDICI, N. P.; DEL POETA, M. New insights on the development of fungal vaccines: from immunity to recent challenges. Memórias do Instituto Oswaldo Cruz, v. 110, n. 8, p. 966–973, 24 nov. 2015.
MINISTÉRIO DA SAÚDE. Situação Epidemiológica. Disponível em: <https://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/c/candidiase-sistemica/situacao-epidemiologica?>. Acesso em: 20 jan. 2025.
MUKHERJEE, P. K. et al. Topical gentian violet compared with nystatin oral suspension for the treatment of oropharyngeal candidiasis in HIV-1-infected participants. AIDS, v. 31, n. 1, p. 81–88, jan. 2017.
NAMI, S. et al. Fungal vaccines, mechanism of actions and immunology: A comprehensive review. Biomedicine & Pharmacotherapy, v. 109, p. 333–344, jan. 2019.
NASIM, N.; SANDEEP, I. S.; MOHANTY, S. Plant-derived natural products for drug discovery: current approaches and prospects. The Nucleus, v. 65, n. 3, p. 399–411, 18 dez. 2022.
NETEA, M. G. et al. Immune defence against Candida fungal infections. Nature Reviews Immunology. Nature Publishing Group, 29 out. 2015.
NGUYEN, T. A. et al. Pichia kudriavzevii (Candida krusei): A systematic review to inform the World Health Organisation priority list of fungal pathogens. Medical Mycology, v. 62, n. 6, 27 jun. 2024.
PRISTOV, K. E.; GHANNOUM, M. A. Resistance of Candida to azoles and echinocandins worldwide. Clinical Microbiology and Infection, v. 25, n. 7, p. 792–798, jul. 2019.
PROŠKOVCOVÁ, Martina et al. Antibiofilm activity of selected plant essential oils from the Lamiaceae family against candida albicans clinical isolates. Annals of Agricultural and Environmental Medicine, v. 28, n. 2, p. 260–266, 2021
QADIR, M. I.; BASHIR, H.; AHMAD, M. H. Human Oropharyngeal Candidiasis: From Etiology to Current Treatment. Critical reviews in immunology, v. 43, n. 3, p. 15–24, 2023.
QUINDÓS, G. et al. Therapeutic tools for oral candidiasis: Current and new antifungal drugs. Medicina Oral, Patología Oral y Cirugía Bucal, v. 24, n. 2, p. e172–e180, 1 mar. 2019.
RAJADURAI, S. G. et al. Comparative Efficacy of Antifungal Agents Used in the Treatment of Oropharyngeal Candidiasis among HIV-Infected Adults: A Systematic Review and Network Meta-Analysis. Journal of Fungi, v. 7, n. 8, p. 637, 5 ago. 2021.
RIBEIRO RIBEIRO, A. L. et al. Oral carriage of Candida species in HIV-infected patients during highly active antiretroviral therapy (HAART) in Belém, Brazil. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, v. 120, n. 1, p. 29–33, 1 jul. 2015.
ROMO, J. A.; KUMAMOTO, C. A. On Commensalism of Candida. J. Fungi, v. 6, n. 16, 2020.
SAMBER, Neha et al. Synergistic anti-candidal activity and mode of action of Mentha piperita essential oil and its major components. Pharmaceutical Biology, v. 53, n. 10, p. 1496–1504, 2015.
SANYAOLU, A. et al. Candida auris: An Overview of the Emerging Drug-Resistant Fungal Infection. Infection & Chemotherapy, v. 54, n. 2, p. 236, 2022.
SENEVIRATNE, C. J. et al. Antifungal Susceptibility in Serum and Virulence Determinants of Candida Bloodstream Isolates from Hong Kong. Frontiers in Microbiology, v. 7, 26 fev. 2016.
SILVA, L. A. et al. Implicações do uso do cigarro eletrônico “vape” na saúde bucal – síntese de evidências atuais. REVISA, p. 661–671, 10 set. 2024.
SPALANZANI, R. N. et al. Clinical and laboratorial features of oral candidiasis in HIV-positive patients. Revista da Sociedade Brasileira de Medicina Tropical, v. 51, n. 3, p. 352–356, 1 abr. 2018.
SZYMAŃSKI, M. et al. Echinocandins – structure, mechanism of action and use in antifungal therapy. Journal of Enzyme Inhibition and Medicinal Chemistry, v. 37, n. 1, p. 876–894, 16 mar. 2022.
TAVERNE-GHADWAL, L. et al. Epidemiology and Prevalence of Oral Candidiasis in HIV Patients From Chad in the Post-HAART Era. Frontiers in Microbiology, v. 13, p. 844069, 17 fev. 2022.
TAYLOR, M.; BRIZUELA, M.; RAJA, A. Oral candidiasis. In: STATPEARLS [Internet]. Treasure Island (FL): StatPearls Publishing, 2025. Disponível em: https://www.statpearls.com.
VILA, T. et al. Oral Candidiasis: A Disease of Opportunity. Journal of Fungi, Vol. 6, Page 15, v. 6, n. 1, p. 15, 16 jan. 2020.
WHALEY, S. G. et al. Azole Antifungal Resistance in Candida albicans and Emerging Non-albicans Candida Species. Frontiers in Microbiology, v. 7, 12 jan. 2017.
WHO. WHO fungal priority pathogens list to guide research, development and public health action. [s.l: s.n.].
WILLIAMS, D.; LEWIS, M. Pathogenesis and treatment of oral candidosis. Journal of Oral Microbiology, 2011.
WU, Y. et al. A newly identified amino acid substitution T123I in the 14α-demethylase (Erg11p) of Candida albicans confers azole resistance. FEMS Yeast Research, v. 17, n. 3, 25 fev. 2017.
WU, Y. et al. Multilocus microsatellite markers for molecular typing of Candida tropicalis isolates. BMC Microbiology, v. 14, n. 1, p. 245, 20 dez. 2014.
YASSIN, M. T.; MOSTAFA, A. A.-F.; AL-ASKAR, A. A. In vitro anticandidal potency of Syzygium aromaticum (clove) extracts against vaginal candidiasis. BMC Complementary Medicine and Therapies, v. 20, n. 1, p. 25, 30 dez. 2020.
YUAN, H. et al. The Traditional Medicine and Modern Medicine from Natural Products. Molecules, v. 21, n. 5, p. 559, 29 abr. 2016.
ZUZA-ALVES, D. L. et al. Evaluation of Virulence Factors In vitro, Resistance to Osmotic Stress and Antifungal Susceptibility of Candida tropicalis Isolated from the Coastal Environment of Northeast Brazil. Frontiers in Microbiology, v. 7, 15 nov. 2016.
ZUZA-ALVES, D. L.; SILVA-ROCHA, W. P.; CHAVES, G. M. An Update on Candida tropicalis Based on Basic and Clinical Approaches. Frontiers in Microbiology, v. 8, 13 out. 2017.
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Copyright (c) 2026 Elisa Montenegro, Ana Barbara Polo, Gustavo Lucas da Silva Lima, Luciana Moreira Chedier, Rodrigo Luiz Fabri
Este trabalho está licenciado sob uma licença Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Autores que publicam nesta revista concordam com os seguintes termos:- Autores mantém os direitos autorais e concedem à revista o direito de primeira publicação, com o trabalho simultaneamente licenciado sob a Licença Creative Commons Attribution que permite o compartilhamento do trabalho com reconhecimento da autoria e publicação inicial nesta revista.
- Autores têm autorização para assumir contratos adicionais separadamente, para distribuição não-exclusiva da versão do trabalho publicada nesta revista (ex.: publicar em repositório institucional ou como capítulo de livro), com reconhecimento de autoria e publicação inicial nesta revista.
- Autores têm permissão e são estimulados a publicar e distribuir seu trabalho online (ex.: em repositórios institucionais ou na sua página pessoal) a qualquer ponto antes ou durante o processo editorial, já que isso pode gerar alterações produtivas, bem como aumentar o impacto e a citação do trabalho publicado (Veja O Efeito do Acesso Livre).
