Conventional and alternative antifungal therapies to oral candidiasis

Candida-associated denture stomatitis is the most common form of oral candidal infection, with Candida albicans being the principal etiological agent. Candida adheres directly or via an intermediary layer of plaque-forming bacteria to denture acrylic. Despite antifungal therapy to treat denture stomatitis, infection is reestablished soon after the treatment ceases. In addition, many predisposing factors have been identified as important in the development of oral candidiasis, including malnourishment, common endocrine disorders, such as diabetis mellitus, antibacterial drug therapy, corticosteroids, radiotherapy and other immunocompromised conditions, such as acquired immunodeficiency syndrome (AIDS). These often results in increased tolerance to the most commonly used antifungals. So this review suggests new therapies to oral candidiasis.82483

Investigation of oral and general health status and IL-1β gene polymorphism as risk factors for oral mucositis in hematopoietic stem cell transplantation patients

The aim of the present study was to analyze the relationship of OM with possible risk factors such as oral health condition, immunological status and IL-1β profile in patients submitted to hematopoietic stem cell transplantation (HSCT). Fifty-four individuals submitted to HSCT were included. All patients received previous dental treatment and photobiomodulation (PBM) as the institutional OM preventive protocol. OM scores, immune status, and IL-1β levels were determined during the conditioning period and at D+3 and D+8 after HSC infusion. IL-1β gene polymorphism was also analyzed during conditioning. Possible associations of OM with risk factors were analyzed using conditional Fisher’s exact test. OM was observed in 34 patients (62.9%) classified as Grade 1 (13 patients/24.1%), Grade 2 (14 patients/25.9%), Grade 3 (3 patients/5.5%), and Grade 4 (4 patients/7.4%). Allogeneic HSCT individuals exhibited a higher OM grade than autologous subjects. Moreover, an association was observed between severe OM and severe gingivitis (p = 0.01), neutropenia (p = 0.03), and leukopenia (p = 0.04). A significant association between OM and lower IL-1β levels was detected at three time points, i.e., conditioning (p = 0.048), D+3 (p = 0.01), and D+8 (p = 0.005). The results showed that IL-1β gene polymorphism was not associated with OM. Our study provided important insights into the scope of OM risk factors in the setting of HSCT. Patients submitted to HSCT with severe gingivitis prior to chemotherapy and with severe neutropenia and leukopenia exhibited a higher OM grade. Further investigation will be necessary to better understand the exact role of IL-1β in the context of OM pathobiology and to validate cytokine analysis in larger cohorts

Function analysis of two-component system VicRK in Streptococcus sanguinis biology

Orientador: Renata de Oliveira Mattos-GranerTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: Streptococcus sanguinis são colonizadores primários dos dentes reconhecidos como microrganismos comensais benéficos da cavidade bucal, pois são capazes de inibir o crescimento de espécies patogênicas, como Streptococcus mutans. S. sanguinis são comumente envolvidos em endocardite bacteriana, embora por mecanismos de patogenicidade ainda não conhecidos. Para colonizar os dentes ou tecidos cardíacos, S. sanguinis devem ser capazes de se estabelecer em biofilmes e de se adaptar às diversas condições de estresse ambiental decorridas da ação de microrganismos competidores e/ou das defesas do hospedeiro. A resposta bacteriana a condições de estresse ambiental é regulada por sistemas reguladores globais de transcrição de dois componentes (SDC), os quais são essenciais para modular o transcriptoma bacteriano durante os processos de colonização e infecção do hospedeiro. O genoma de S. sanguinis SK36 apresenta 14 desses sistemas. Através de análises de BLAST, identificou-se um SDC com alta similaridade ao sistema VicRK (vic de virulence control), o qual regula fatores de virulência e é conservado em diversas espécies de bactérias Gram-positivas, como S. mutans e Streptococcus pneumoniae. O objetivo deste trabalho foi caracterizar a função do sistema VicRK na biologia de S. sanguinis, através da análise dos efeitos da inativação de vicK em diversas características bacterianas possivelmente associadas à virulência e à formação de biofilmes. Para isto, foi construído um mutante knock-out do gene vicK a partir da cepa SK36, o qual foi designado SKvicK. SKvicK foi comparado à cepa selvagem quanto à capacidade de formação de biofilmes e quanto às características que influenciam na capacidade de colonização (hidrofobicidade, atividade autolítica e sensibilidade ao estresse oxidativo) em diferentes condições atmosféricas. Também foram comparados, entre as cepas, os padrões de expressão de genes com possível função de virulência, cujos ortólogos são regulados por VicRK nas espécies S. mutans e/ou S. pneumoniae. Estes incluem genes relacionados à formação de biofilmes e biogênese da parede celular (ssapcsB, lysM, gtfP), à resposta ao estresse oxidativo e produção de peróxido de hidrogênio (sodA, spxB, ccpA). A inativação de vicK inibiu claramente a formação inicial de biofilmes. Além disto, SKvicK demonstrou maior sensibilidade ao estresse oxidativo e maior hidrofobicidade celular. A inativação de vicK também inibiu, de forma significativa, a transcrição dos genes pcsB, lysM, spxB e comE. Estes dados indicam que VicRK regula diversas funções biológicas de S. sanguinis importantes para a colonização de humanosAbstract: Streptococcus sanguinis are primary colonizers of the teeth and recognized as beneficial commensal microorganisms of the oral cavity because they are able to inhibit the growth of pathogenic species such as Streptococcus mutans. S. sanguinis are commonly involved in the infective endocarditis, although pathogenic mechanisms are still unknown. S. sanguinis are able to establish in biofilms and to adapt among various environmental stress conditions from competing microorganisms and/or from host defenses during colonization of enamel or endothelial tissues. Bacterial responses from environmental stress conditions are regulated by two-component global regulatory systems (TCS), which are essential to modulate the bacterial transcriptome during colonization and infection of the host. S. sanguinis SK36 genome contains at least 14 TCS. Through BLAST analyses, we identified a TCS with high similarity to VicRK system (vic from virulence control), which regulates virulence factors and is conserved in several species of gram-positive bacteria such as S. mutans and Streptococcus pneumoniae. The aim of this study was to characterize the role of VicRK system in S. sanguinis biology, by analyzing the effects of vicK inativation on several characteristics potentially associated with bacterial virulence and biofilm formation. For this purpose, vicK mutant gene knock-out was obtained from strain SK36 and it was designated SKvicK. SKvicK was compared to the wild-type strain about the ability to form biofilms and cellular traits which influence in the ability of host colonization (hydrophobicity, autolytic activity and sensitivity to oxidative stress) under diverse atmospheric conditions. Gene expression was also compared in the strains because these genes are potencially involved in virulence, whose orthologs are regulated by VicRK system in S. mutans and S. pneumoniae species. These include genes involved in biofilm formation and cell wall biogenesis (ssapcsB, lysM, gtfP), oxidative stress response and production of hydrogen peroxide (sodA, spxB, ccpA). The inactivation of vicK inhibited the initial formation of biofilms. Moreover, SKvicK showed increased sensitivity to oxidative stress and cell hydrophobicity. vicK gene inativation also signicantly down-regulated transcription of pcsB, lysM, spxB and comE. These data indicate that VicRK regulates several biological functions relevant for S. sanguinis colonizationDoutoradoEstomatologiaDoutor em Estomatopatologi