Structural and functional characterization of the recombinant thioredoxin reductase from Candida albicans as a potential target for vaccine and drug design.

The thioredoxin system plays a critical role in maintaining the cytoplasm redox state, participating in functions that are important to the cellular viability of fungi. Although functional and structural information on targets in human pathogenic fungi has been scarcely described in the literature, such studies are essential for in silico drug design and biotechnological applications. Therefore, the aims of the present study were to produce recombinant proteins of the thioredoxin system from Candida albicans and evaluate their possible use as prophylactic or alternative therapies against the most important pathogenic fungus associated with nosocomial infections. We focused on biochemical and structural analyses of recombinant thioredoxin reductase from C. albicans with His-tag (CaTrxR-His) for further biotechnology applications. Heterologous CaTrxR-His was efficiently expressed in the soluble fraction of the Escherichia coli lysate. CaTrxR-His was obtained with a high level of purity and presented specific enzymatic activity. Conformational changes of the protein were observed at different pHs and temperatures, with higher thermal stability at pH 8.0. The CaTrxR-His vaccine was shown to effectively induce high levels of CaTrxR-specific immunoglobulin G antibodies in Balb/c mice and reduce the renal fungal burden of experimental disseminated candidiasis in mice. These data may greatly impact future development strategies for vaccine and drug designs against C. albicans infection.

Microbicidal activity of neutrophils is inhibited by isolates from recurrent vaginal candidiasis (RVVC) caused by Candida albicans through fungal thioredoxin reductase.

Vulvovaginal candidiasis (VVC) is characterized by an infection of the vulva and vagina, mainly caused by Candida albicans, a commensal microorganism that inhabits the vaginal, digestive, and respiratory mucosae. Vulvovaginal candidiasis affects approximately 75% of women, and 5% develop the recurrent form (RVVC). The aim of the present study was to evaluate whether neutrophils microbicidal response is triggered when activated with RVVC isolates caused by C. albicans. Our results showed that RVVC isolates induced neutrophil migration but significantly decrease the microbicidal activity of neutrophils, compared with VVC and ASS isolates. The microbicidal activity of neutrophils is highly dependent on the production of reactive oxygen species/reactive nitrogen species (ROS/RNS). However, this isolate induced detoxification of ROS/RNS produced by neutrophils, reflected by the high level of thiol groups and by the oxygen consumption. Therefore, RVVC isolates induced biochemical changes in the inflammatory response triggered by neutrophils, and these effects were mainly related to the detoxification of ROS/RNS through the thioredoxin reductase (TR), a key antioxidant enzyme in fungi. This might be one of the resistance mechanisms triggered by RVVC caused by C. albicans.

A sífilis na gestação e sua influência na morbimortalidade materno-infantil: uma revisão integrativa / Syphilisin pregnancy and their influence on fetal and maternal morbidity: an integrative review / La sífilis en el embarazo y su influencia en la morbilidad y mortalidad materna e infantil: una revisión integradora

Objetivando identificar os fatores base na prevenção da sífilis gestacional e suas complicações materno-fetais, foi realizado uma revisão integrativa de literatura. Utilizando-se as bases de dados SciELO e LILACS, foram selecionados 15 artigos publicados entre o período de 2006 a 2020, bem como os dados obtidos apósa realização de uma intervenção acerca do tema junto as gestantes da UBS do bairro Santa Rita, no Município de Imperatriz-MA. Os fatoresbase na prevenção da sífilis gestacional incluem medidas de profilaxia da doença, adesão adequada ao pré-natal para diagnóstico precoce, instituição de tratamento específico, concordância da gestante à terapêutica e acompanhamento por equipe de saúde multiprofissional após o quadro. A promoção de conhecimento sobre a sífilis gestacional e suascomplicações tanto para as gestantes quanto para os profissionais de saúde que avaliam e tratam esse grupo é fundamental para a prevenção dessa doença e seus agravos. (AU)

Aiming to identify the basic factors in the prevention of gestational syphilis and its maternal-fetal complications, an integrative literature review was carried out. Using the SciELOand LILACS databases, 22 articles published between the period 2006 to 2020 were selected, as well the data obtained after an intervention on the topic with pregnant women at the UBS in the Santa Rita neighborhood, in the city. of Imperatriz-MA. The basicfactors in the prevention of gestational syphilis include measures to prevent the disease, adequate adherence to prenatal care for early diagnosis, institution of specific treatment, agreement of the pregnant woman to therapy and follow-up by a multidisciplinary health team after the condition. The promotion of knowledge about gestational syphilis and its complications both for pregnant women and for health professionals who assess and treat this group is essential for the prevention of this disease and its problems.

Con el objetivo de identificar los factores básicos en la prevención de la sífilis gestacional y sus complicaciones materno-fetales, se realizó una revisión integradora de la literatura. Utilizando las bases de datos SciELO y LILACS, se seleccionaron 15 artículos publicados entre el período 2006 a 2020, así como los datos obtenidos luego de una intervención sobre el tema con gestantes en la UBS del barrio Santa Rita, en la ciudad de Emperatriz-MA. Los factores básicos en la prevención de la sífilis gestacional incluyen las medidas de prevención de la enfermedad, la adecuada adherencia a la atención prenatal para el diagnóstico precoz, la institución de un tratamiento específico,la aceptación de la gestante a la terapia y el seguimiento por un equipo multidisciplinario de salud después de la afección. La promoción del conocimiento sobre la sífilis gestacional y sus complicaciones tanto a las mujeres embarazadas como a los profesionales de la salud que evalúan y tratan a este grupo es fundamental para la prevención de esta enfermedad y sus problemas.

Candida albicans PROTEIN PROFILE CHANGES IN RESPONSE TO THE BUTANOLIC EXTRACT OF Sapindus saponariaL.

Candida albicans is an opportunistic human pathogen that is capable of causing superficial and systemic infections in immunocompromised patients. Extracts of Sapindus saponaria have been used as antimicrobial agents against various organisms. In the present study, we used a combination of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) to identify the changes in protein abundance of C. albicans after exposure to the minimal inhibitory concentration (MIC) and sub-minimal inhibitory concentration (sub-MIC) of the butanolic extract (BUTE) of S. saponaria and also to fluconazole. A total of six different proteins with greater than 1.5 fold induction or repression relative to the untreated control cells were identified among the three treatments. In general, proteins/enzymes involved with the glycolysis (GPM1, ENO1, FBA1), amino acid metabolism (ILV5, PDC11) and protein synthesis (ASC1) pathways were detected. In conclusion, our findings reveal antifungal-induced changes in protein abundance of C. albicans. By using the previously identified components of the BUTE of S. saponaria(e.g., saponins and sesquiterpene oligoglycosides), it will be possible to compare the behavior of compounds with unknown mechanisms of action, and this knowledge will help to focus the subsequent biochemical work aimed at defining the effects of these compounds.

Adhesion and biofilm formation in artificial saliva and susceptibility of yeasts isolated from chronic kidney patients undergoing haemodialysis.

Yeasts of the genera Candida and Saccharomyces are opportunist pathogens and cause oral lesions, especially in immunocompromised patients. This study assessed yeasts isolated from chronic kidney patients undergoing haemodialysis for their adhesion capacity, biofilm formation and susceptibility to antifungal agents. Ten isolates of Candida spp. and one isolate of Saccharomyces cerevisiae were tested for adhesion to buccal epithelial cells (BECs), adhesion and formation of biofilm in artificial saliva and their susceptibility profile to antifungal agents. Adhesion and biofilm formation were undertaken in polystyrene plates with artificial saliva, whilst susceptibility to antifungal agents was evaluated by broth microdilution. Candida parapsilosis had the highest adhesion index in BECs (154.55 ± 22.13) and Candida rugosa was the species with the highest adhesion capacity (18 398  Abs cm(-2)) in abiotic surface with artificial saliva. Candida albicans provided the greatest biofilm formation (2035  Abs cm(-2) ± 0.09) but was revealed to be susceptible to the five antifungal agents under analysis. However, some non-albicans Candida isolates showed a lower susceptibility for the antifungal agents itraconazole, fluconazole and voriconazole. All of the species were sensitive to amphotericin B and nystatin. The current analysis showed that yeasts isolated from the mouth of chronic kidney patients undergoing haemodialysis varied significantly with regard to their capacity for adherence, biofilm formation and susceptibility to antifungal agents, underscoring the high virulence of non-albicans Candida species.

In vitro effect of Paullinia cupana (guaraná) on hydrophobicity, biofilm formation, and adhesion of Candida albicans' to polystyrene, composites, and buccal epithelial cells.

OBJECTIVE: In vitro evaluation of the effect of guaraná (GUAR) on cell surface hydrophobicity (CSH), on biofilm formation, and on adhesion of C. albicans to polystyrene, to composite resins, and to buccal epithelial cells (BEC). MATERIALS AND METHODS: Lyophilised aqueous extract of GUAR was tested on C. albicans ATCC (90028). The effect of GUAR was evaluated by examining the CSH of C. albicans, as determined by microbial adhesion to hydrocarbons test, by assessing biofilm production and through adhesion assays (microplates of polystyrene, BEC and composites). One nanoparticle (Z350(®)) and two microhybrid (LLis(®), Opallis(®)) composites were tested. Scanning electron microscopy (SEM) was used to analyse adhesion of C. albicans composites. Assays were performed in triplicate and the results analysed by Chi-square test, Kruskal-Wallis test and Dunn's Multiple Comparison post hoc test at 5% significance level. RESULTS: GUAR did not inhibit growth of C. albicans at any concentration, but it reduced adhesion to polystyrene surface (p < 0.001). Exposure to GUAR did not change CSH and biofilm formation, but it increased adhesion of C. albicans to the nanoparticle composite (p = 0.042) and reduced its adhesion to BEC (p < 0.001). SEM confirmed an aggregatory pattern of adhesion of C. albicans to composites. CONCLUSION: GUAR increased the adhesion of C. albicans to the surface of the nanoparticle composite. However, it reduced the adhesion of C. albicans to BEC and to polystyrene, which reveals its potential use in prevention of oral diseases.