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Master's Dissertation
DOI
https://doi.org/10.11606/D.58.2020.tde-06102022-165151
Document
Author
Full name
Renata Klemp Orlandini
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2020
Supervisor
Committee
Lourenço, Alan Grupioni (President)
Motta, Ana Carolina Fragoso
Portela, Maristela Barbosa
Rosa, Adalberto Luiz
Title in Portuguese
Prevalência e virulência de Candida spp. em indivíduos com tuberculose e suas relações com proteínas antifúngicas salivares
Keywords in Portuguese
Candida spp
Proteínas antifúngicas salivares
Tratamento antituberculose
Tuberculose
Virulência de Candida spp
Abstract in Portuguese
A patogênese da tuberculose (TB) associada ao seu tratamento antimicrobiano de longa duração tornam-se fatores preditivos para infecções fúngicas. Alguns estudos demonstraram uma alta prevalência de espécies de Candida em pacientes com tuberculose (TB), o que pode estar associado à terapia antimicrobiana, ao aumento da virulência de Candida spp. ou ao desequilíbrio das secreções antifúngicas salivares endógenas. Por meio de um estudo de coorte, a prevalência, a virulência de Candida spp e as concentrações de proteínas antifúngicas salivares, lactoferrina (Lf) e histatina 5 (Hist5), foram avaliadas na cavidade oral de 30 pacientes com TB em diferentes estágios do seu tratamento. Esses resultados foram comparados com aqueles encontrados em 60 indivíduos sistemicamente saudáveis (controle). Amostras de enxágue bucal e saliva foram coletadas antes de 45 dias e após 120 dias de tratamento de pacientes com TB. Essa coleta foi realizada apenas uma única vez em pacientes sistemicamente saudáveis. Candida spp foram identificadas por ensaios de polimorfismo de comprimento de fragmento de restrição e os seguintes fatores de virulência foram estudados: produção de fosfolipase C e proteinase, capacidade de formação de biofilme e formação de hifas de Candida spp. Na saliva verificaram-se as concentrações de Lf e Hist-5 por ELISA. O diagnóstico clínico da TB e seu tempo de tratamento estiveram associados à maior carga fúngica de Candida spp. (p<0,0001) e a maior prevalência de Candida não-albicans (p=0,0003). Também verificamos aumento nos fatores de virulência, expressos pela produção de fosfolipase C de Candida albicans (p=0,0015) e de espécies não-albicans (p= 0,0165) em pacientes com TB. A produção de proteinase de Candida albicans também foi maior em pacientes com TB quando comparados àquelas isoladas de pacientes sistemicamente saudáveis (p=0,0032. Os níveis salivares de Lf estiveram maiores em pacientes com TB (p=0,0001). Em conclusão observamos que o diagnóstico da TB e seu tratamento antimicrobiano estão associados com o aumento da carga fúngica, virulência de Candida spp e maior prevalência de espécies não-albicans, o que atenta para o maior risco de lesões orais e disseminações sistêmicas nesses pacientes.
Title in English
Prevalence and virulence of Candida spp. in patients with tuberculosis and their associations with salivary antifungal proteins
Keywords in English
Anti-tuberculosis treatment
Candida spp
Salivary antifungal proteins
Tuberculosis
Virulence of Candida spp
Abstract in English
The pathogenesis of tuberculosis (TB) and its long-term antimicrobial treatment are predictive factors for fungal diseases. Some studies have demonstrated a high prevalence of Candida species in patients with TB, which may be associated with antimicrobial therapy, with an increase in the virulence of Candida spp., or the imbalance of endogenous salivary antifungal secretions. Through a cohort study, the prevalence, virulence of Candida spp, and concentrations of salivary antifungal proteins, lactoferrin (Lf) and histatin 5 (Hist5) were evaluated in the oral cavity of 30 TB patients at different stages of their treatment. These results were compared with those found in 60 systemically healthy (controls). Saliva and oral rinse samples were collected before 45 days and after 120 days of treatment from patients with TB, and once in systemically healthy patients. Restriction fragment length polymorphism assays were performed to identify Candida spp, and the following virulence factors (phospholipase C and proteinase production, biofilm formation capacity, and hyphae formation) of Candida spp were studied. Salivary concentrations of Lf and Hist 5 were determined by enzyme-linked immunosorbent assay (ELISA). TB patients had higher fungal burden of Candida spp. (p <0.0001), and prevalence of non-albicans Candida (NAC) (p = 0.0003) than healthy patients. In addition, longer phase of TB treatment (120 days) was also associated to these results. We also observed an increase in virulence factors, expressed by the production of phospholipase C from Candida albicans (p = 0.0015) and NAC (p = 0.0165) in patients with TB. The proteinase production was higher in C. albicans from TB patients when compared to those systemically healthy patients (p = 0.0032). Lf salivary levels were also higher in TB patients than in healthy patients (p = 0.0001). In conclusion, we observed that the diagnosis of TB and their treatment were associated with high burden fungal, Candida spp virulence and prevalence of NAC. These findings alert for the high-risk for the occurrence of oral lesions and systemic dissemination in TB patients.
 
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Publishing Date
2022-10-07
 
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