Publications by authors named "Luiz Carlos Alves"

63 Publications

Detection of Leishmania infantum amastigotes in neutrophil from peripheral blood in a naturally infected dog.

Rev Bras Parasitol Vet 2021 9;30(3):e004821. Epub 2021 Jul 9.

Laboratório de Biologia Celular e Molecular, Departamento de Parasitologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz - FIOCRUZ-PE, Pernambuco, PE, Brasil.

Canine visceral leishmaniasis (CVL) is a zoonotic disease of high lethality caused by Leishmania infantum in the Americas. In the infected dog, the amastigotes are scarce in blood, especially in the late phase of the disease. This study aimed to report a rare case of L. infantum amastigotes found in neutrophils from peripheral blood of a naturally infected dog in terminal phase of CVL, also describing its clinical status before and after treatment with miltefosine 2%. The dog, which presented as polysymptomatic and with classical signs and symptoms of CVL was submitted to the following tests: Dual Path Platform (DPP) rapid test, ELISA and parasitological examination of peripheral blood. Hematological and biochemical parameters were obtained before and after treatment. All diagnostic tests were positive for CVL. The identification of L. infantum amastigotes inside neutrophils from peripheral blood was confirmed through microscopy, and the species was confirmed by molecular analysis. At the end of the treatment, peripheral parasitemia was not detected, and improvements were observed in clinical and laboratorial parameters. Finally, this atypical finding can be used as example to raise discussions about the real immunological role of neutrophils in late phases of CVL and its clinical/therapeutic implications.
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http://dx.doi.org/10.1590/S1984-29612021060DOI Listing
July 2021

Structural improvement of new thiazolyl-isatin derivatives produces potent and selective trypanocidal and leishmanicidal compounds.

Chem Biol Interact 2021 Aug 24;345:109561. Epub 2021 Jun 24.

Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-535, Recife, PE, Brazil.

Neglected diseases are a group of transmissible diseases that occur mostly in countries in tropical climates. Among this group, Chagas disease and leishmaniasis stand out, considered threats to global health. Treatment for these diseases is limited. Therefore, there is a need for new therapies against these diseases. In this sense, our proposal consisted of developing two series of compounds, using a molecular hybridization of the heterocyclic isatin and thiazole. The isatin and thiazole ring are important scaffold for several biological disorders, including antiparasitic ones. Herein, thiazolyl-isatin has been synthesized from respective thiosemicarbazone or phenyl-thiosemicarbazone, being some of these new thiazolyl-isatin toxic for trypomastigotes without affecting macrophages viability. From this series, compounds 2e (IC = 4.43 μM), 2j (IC = 2.05 μM), 2l (IC = 4.12 μM) and 2m (1.72 μM) showed the best anti-T. cruzi activity for trypomastigote form presenting a selectivity index higher than Benznidazole (BZN). Compounds 2j, 2l and 2m were able to induce a significantly labelling compatible with necrosis in trypomastigotes. Analysis by scanning electron microscopy showed that T. cruzi trypomastigote cells treated with the compound 2m from IC concentrations, promoted changes in the shape, flagella and surface of body causing of the parasite dead. Concerning leishmanicidal evaluation against L. amazonensis and L. infantum, compounds 2l (IC = 7.36 and 7.97 μM, respectively) and 2m (6.17 and 6.04 μM, respectively) showed the best activity for promastigote form, besides showed a higher selectivity than Miltefosine. Thus, compounds 2l and 2m showed dual in vitro trypanosomicidal and leishmanicidal activities. A structural activity relationship study showed that thiazolyl-isatin derivatives from phenyl-thiosemicarbazone (2a-m) were, in general, more active than thiazolyl-isatin derivatives from thiosemicarbazone (1a-g). Crystallography studies revealed a different configuration between series 1a-g and 2a-m. The configuration and spatial arrangement divergent between the two sub-series could explain the improved biological activity profile of 2a-m sub-series.
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http://dx.doi.org/10.1016/j.cbi.2021.109561DOI Listing
August 2021

Aspects related to positivity for schistosomiasis: a cross-sectional study in a low prevalence area in Alagoas, Brazil, 2020.

Epidemiol Serv Saude 2021 May 31;30(2):e2020520. Epub 2021 May 31.

Fundação Instituto Oswaldo Cruz, Departamento de Parasitologia, Recife, PE, Brasil.

Objective: To analyze aspects related to schistosomiasis positivity in an area of low prevalence in Brazil.

Methods: This was a cross-sectional study, carried out in the first half of 2020, where we analyzed the proportion of positivity, according to the number of Kato-Katz slides, the diagnostic performance of the test and positivity estimates based on data from the Schistosomiasis Surveillance and Control Program Information System (SISPCE).

Results: 2,088 slides from 348 individuals were analyzed, with proportion of positivity of 11.8%, 26.7% and 31.0% for 1, 4 and 6 slides analyzed, respectively. There was excellent agreement (Kappa = 0.91) between the readings of 4 and 6 slides. The SISPCE data was estimated to be underreported by up to 2.1 times.

Conclusion: Increasing the number of slides increased Kato-Katz positivity, which can contribute to maximizing the control of the disease as a Public Health problem.
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http://dx.doi.org/10.1590/S1679-49742021000200005DOI Listing
May 2021

Structural design, synthesis and anti-Trypanosoma cruzi profile of the second generation of 4-thiazolidinones chlorine derivatives.

Chem Biol Interact 2021 Aug 21;345:109514. Epub 2021 May 21.

Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Pernambuco, 50740-520, Recife, PE, Brazil. Electronic address:

Chagas disease causes more deaths in the Americas than any other parasitic disease. Initially confined to the American continent, it is increasingly becoming a global health problem. In fact, it is considered to be an "exotic" disease in Europe, being virtually undiagnosed. Benznidazole, the only drug approved for treatment, effectively treats acute-stage Chagas disease, but its effectiveness for treating indeterminate and chronic stages remains uncertain. Previously, our research group demonstrated that 4-thiazolidinones presented anti-T. cruzi activity including in the in vivo assays in mice, making this fragment appealing for drug development. The present work reports the synthesis and anti-T. cruzi activities of a novel series of 4-thiazolidinones derivatives that resulted in an increased anti-T. cruzi activity in comparison to thiosemicarbazones intermediates. Compounds 2c, 2e, and 3a showed potent inhibition of the trypomastigote form of the parasite at low cytotoxicity concentrations in mouse splenocytes. Besides, all the 2c, 2e, and 3a tested concentrations showed no cytotoxic activity on macrophages cell viability. When macrophages were submitted to T. cruzi infection and treated with 2c and 3a, compounds reduced the release of trypomastigote forms. Results also showed that the increased trypanocidal activity induced by 2c and 3a is independent of nitric oxide release. Flow cytometry assay showed that compound 2e was able to induce necrosis and apoptosis in trypomastigotes. Parasites treated with the compounds 2e, 3a, and 3c presented flagellum shortening, retraction and curvature of the parasite body, and extravasation of the internal content. Together, these data revealed a novel series of 4-thiazolidinones fragment-based compounds with potential effects against T. cruzi and lead-like characteristics.
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http://dx.doi.org/10.1016/j.cbi.2021.109514DOI Listing
August 2021

A first, naturally occurring substitution at the second pyrethroid receptor of voltage-gated sodium channel of Aedes aegypti.

Pest Manag Sci 2021 Jun 25;77(6):2887-2893. Epub 2021 Feb 25.

Department of Medical Entomology, National Institute of Infectious Diseases, Tokyo, Japan.

Background: Aedes aegypti is a remarkably effective mosquito vector of epidemiologically important arboviral diseases including dengue fever, yellow fever and Zika. The present spread of resistance against pyrethroids, the primary insecticides used for mosquito control, in global populations of this species is of great concern. The voltage-gated sodium channel (VGSC) in the nervous system is the known target site of pyrethroids in insects. Past studies have revealed several amino-acid substitutions in this channel that confer pyrethroid resistance, which are known as knockdown resistance (kdr) mutations.

Results: This study investigated a laboratory colony of Ae. aegypti, MCNaeg, established from larvae collected in Rio de Janeiro, Brazil in 2016. The MCNaeg colony showed strong resistance against pyrethroids without laboratory selection. Of the two VGSC gene haplotypes present within this colony, one harbored three known kdr mutations, V410L, V1016I, and F1534C, and the other harbored only the known F1534C mutation. In latter haplotype, we also found novel amino-acid substations including V253F. Previous molecular modeling and electrophysiological studies suggest that this residue serves a pyrethroid-sensing site in the second receptor, PyR2. Our genetical analysis showed that the haplotype harboring V253F and F1534C is associated with equal or slightly stronger resistance than the other triple kdr haplotype to both Type I and Type II pyrethroids.

Conclusion: The novel substitution V253F is potentially involved in pyrethroid resistance in Ae. aegypti. Further studies are needed to elucidate the role of this substitution in the pyrethroid susceptibility of VGSC. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.6324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247860PMC
June 2021

Evaluation of marginal sealing quality of restorations with low shrinkage composite resins.

J Clin Exp Dent 2020 Dec 1;12(12):e1100-e1108. Epub 2020 Dec 1.

PhD, Associate teacher - UFPE - Federal University of Pernambuco, Department of Prosthetic Dentistry and Maxillofacial Surgery, 1235 Professor Moraes Rego Ave, Recife, PE, 50670901, Brazil.

Background: This study compared the quality of marginal sealing in the gingival wall of class II preparations of two low-shirinkage resins of the bulk fill type with a conventional resin isolated or associated with a glass ionomer cement (GIC).

Material And Methods: 40 human molars were divided into 4 groups and 80 occlusal-mesial and occlusal-distal restorations were performed with the following materials: SureFil SDR flow, Filtek Bulk Fill Posterior, Z250 resins and Riva Light Cure GIC. 40 restorations were evaluated in Scanning Electron Microscopy (SEM) with Elemental Microanalysis Spectrometry (EDS) initially and the remainder after a period of 6 months of aging in a 37 ± 5°C oven. An average of the silver penetration at each restoration was obtained in the two evaluations and the results were statistically analyzed in a descriptive and inferential way, through the paired t-Student and one-way ANOVA F-test.

Results: There were no significant statistical differences between the materials with respect to silver nanoinfiltration, except for the Bulk Fill Posterior/3M ESPE resin compared to the GIC and conventional resin in the final evaluation.

Conclusions: The low shrinkage resins showed a similar behavior in relation to the marginal sealing quality observed in the GIC or composite resin with the incremental technique, also presenting the advantage of simplicity in the technique of confection of the restorations and reduction of the time of work. Resin composites, Bulk fill, dental restorations, marginal quality, adhesion.
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http://dx.doi.org/10.4317/jced.57402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700789PMC
December 2020

New epidemiological profile of schistosomiasis from an area of low prevalence in Brazil.

Rev Soc Bras Med Trop 2020 21;53:e20200335. Epub 2020 Oct 21.

Fundação Oswaldo Cruz, Instituto Aggeu Magalhães, Programa de Pós-Graduação Stricto Sensu em Biociência e Biotecnologia em Saúde, Recife, PE, Brasil.

Introduction: Schistosomiasis, caused by infection from Schistosoma mansoni, is a disease that represents an important public health problem for Brazil, especially for states in the Northeast region. Thus, the aim of this study is to present a new epidemiological profile for the disease in a municipality with low prevalence in the state of Alagoas, Brazil.

Methods: A cross-sectional study was conducted through a coproparasitological and malacological survey. A structured questionnaire was applied to the study participants to survey possible risk factors and a spatial analysis (kernel density) was used to measure the risk of infection.

Results: Of the 347 participants, 106 (30.5%) were infected by Schistosoma mansoni, most of them from the urban area of the municipality (68.9%; 73/106). A 3-fold risk of infection was found for individuals living in the urban area and a risk of 2.15 times for self-declared farmers. Biomphalaria glabrata and B. straminea were the species found in the municipality, but no animals were diagnosed as infected by the parasite. Spatial analysis showed a random distribution of vectors and human cases of the disease, and the formation of two clusters of human cases in the urban area was seen.

Conclusions: A new epidemiological profile for schistosomiasis from S. mansoni infection was presented in a municipality of low endemicity: a high proportion of positive individuals in the urban area; presence of snails without positive diagnosis for S. mansoni infection; random distribution of vectors and human cases; and absence of association between classical risk factors and human infection.
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http://dx.doi.org/10.1590/0037-8682-0335-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580273PMC
October 2020

Ultrastructural changes caused by the combination of intravenous immunoglobulin with meropenem, amikacin and colistin in multidrug-resistant Acinetobacter baumannii.

Microb Pathog 2020 Dec 9;149:104437. Epub 2020 Oct 9.

Laboratório de Biologia Celular e Molecular, Departamento de Parasitologia, Instituto Aggeu Magalhães (FIOCRUZ/PE), Recife, PE, Brasil; Laboratório de Imunopatologia KeizoAsami/Universidade Federal de Pernambuco, Av. Prof. Moraes Rego, S/n - Cidade Universitária, Recife, PE, 50740, Brasil; Pós-graduação em Medicina Tropical, Universidade Federal de Pernambuco, Av. Prof. Moraes Rego, S/n - Cidade Universitária, Recife, PE, 50740, Brasil.

Acinetobacter baumannii is an opportunistic pathogen associated with increased morbidity and mortality in Healthcare-associated infections (HAI). Combination antimicrobial therapy, meropenem, amikacin and colistin, has been used as an alternative in multidrug-resistant (MDR) A. baumannii infections due to reduced treatment options. However, these combinations are not always effective and exhibit high toxicity. Empiric therapy of intravenous immunoglobulin (IVIG) associated with antimicrobials has shown promising results in bacterial infections, considering the immunomodulatory action of IVIG. Thus, the aim of this study was to determine the combined antimicrobial action and to describe the ultrastructural changes caused in ten MDR A. baumannii isolates submitted to IVIG alone and in combination with colistin, meropenem and amikacin. Minimum Inhibitory Concentration (MIC) of antimicrobials and checkerboard were determined. Isolates were submitted to 4 mg/mL of IVIG alone and in combination with different synergistic sub-MIC of antimicrobials tested, and processed for scanning electron microscopy. Nine bacterial isolates showed meropenem-resistant, two isolates had colistin-intermediate, and four isolates were considered intermediate to amikacin. Synergism in five isolates for meropenem/amikacin and meropenem/colistin were observed. Bacterial cells submitted to IVIG and meropenem, amikacin and colistin presented several ultrastructural changes, such as cell elongation and rupture, membrane roughness, incomplete cell division, cell surface "bubbles" and "depression". A. baumannii isolates presented high resistance to meropenem and synergism among evaluated antimicrobials. In addition, it was possible to verify in vitro that IVIG associated with meropenem, amikacin and colistin is a promising alternative for MDR A. baumannii infections. Thus, these data support the continued empirical use and stimulate in vivo analyzes with IVIG to search for new therapeutic options for HAI.
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http://dx.doi.org/10.1016/j.micpath.2020.104437DOI Listing
December 2020

Antimicrobial activity and biofilm inhibition of riparins I, II and III and ultrastructural changes in multidrug-resistant bacteria of medical importance.

Microb Pathog 2020 Dec 30;149:104529. Epub 2020 Sep 30.

Laboratory of Molecular and Cellular Biology, Department of Parasitology, Institute Aggeu Magalhães - FIOCRUZ/PE (Av. Prof. Moraes Rego, S/n - Cidade Universitária, Recife/PE, 50670-420, Brazil; Electronic Microscopy, Laboratory of Immunopathology Keizo Asami, Federal University of Pernambuco (Av. Prof. Moraes Rego, 1235 - Cidade Universitária, Recife, PE, 50670-901, Brazil.

Natural products have been used to treat various infections; however, the development of antimicrobials has made natural products in disuse. Riparin I, II and III are natural alkamide isolated from Aniba riparia (Ness) Mez (Lauraceae), that exhibit economic importance and it is used in traditional medicine, and popularly known as "louro". This study investigated the cytotoxicity, antimicrobial and antibiofilm activity, and ultrastructural changes in vitro by riparins I, II and III in Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. We analyzed the cytotoxicity by MTT assay in Vero cells and hemolytic action verified in human erythrocytes. The antimicrobial activity was determined by microdilution in broth against ATCC strains, identifying the susceptible species. Subsequently, only the MDR isolates of sensitive bacterial species were evaluated regarding its biofilm formation and ultrastructural changes. Riparin I presented low cytotoxicity and hemolytic percentage ranging from of 9.01%-12.97%. Only the riparin III that showed antimicrobial activity against MDR clinical isolates, and significant reduction in biofilm formation in S. aureus. Moreover, the riparin III promoted ultrastructural changes in bacterial cells, such as elongated cellular without bacterial septum, cells with a rugged appearance on the cell surface and cytoplasmic material extravasation. As has been noted riparin III has an inhibitory potential against biofilm formation in S. aureus, besides having antimicrobial activity and promoting ultrastructural changes in MDR clinical isolates. Thus, riparin III is an interesting alternative for further studies aiming to develop new therapeutic options.
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http://dx.doi.org/10.1016/j.micpath.2020.104529DOI Listing
December 2020

Production and partial purification by PEG/citrate ATPS of a β-galactosidase from the new promising isolate URM 7803.

Prep Biochem Biotechnol 2021 9;51(3):289-299. Epub 2020 Sep 9.

Department of Morphology and Animal Physiology, Federal Rural University of Pernambuco, Recife, Brazil.

β-Galactosidase production, partial purification and characterization by a new fungal were investigated. Partial purification was performed by aqueous two-phase system (ATPS) using polyethylene glycol (PEG) molar mass, PEG concentration, citrate concentration and pH as the independent variables. Purification factor (), partition coefficient () and yield () were the responses. After identification by rDNA sequencing and classification as URM 7803, this isolate achieved a maximum cell concentration and β-galactosidase activity of 0.48 g/L and 462.1 U/mL, respectively. β-Galactosidase partitioned preferentially for bottom salt-rich phase likely due to hydrophobicity and volume exclusion effect caused in the top phase by the high PEG concentration and molar mass. The highest value of (12.94) was obtained using 24% (w/w) PEG 8000 g/mol and 15% (w/w) citrate, while that of (79.76%) using 20% (w/w) PEG 400 g/mol and 25% (w/w) citrate, both at pH 6. The enzyme exhibited optimum temperature in crude and ATPS extracts in the ranges 35-50 °C and 40-55 °C, respectively, and optimum pH in the range 3.0-4.5, with a fall of enzyme activity under alkaline conditions. Some metal ions and detergents inhibited, while others stimulated enzyme activity. Finally, URM 7803 β-galactosidase showed a profile suitable for prebiotics production.
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http://dx.doi.org/10.1080/10826068.2020.1815054DOI Listing
July 2021

Dual Parasiticidal Activities of Phthalimides: Synthesis and Biological Profile against Trypanosoma cruzi and Plasmodium falciparum.

ChemMedChem 2020 11 19;15(22):2164-2175. Epub 2020 Oct 19.

Departamento de Ciências Farmacêuticas Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-535, Recife, PE, Brazil.

Chagas disease and malaria are two neglected tropical diseases (NTDs) that prevail in tropical and subtropical regions in 149 countries. Chagas is also present in Europe, the US and Australia due to immigration of asymptomatic infected individuals. In the absence of an effective vaccine, the control of both diseases relies on chemotherapy. However, the emergence of parasite drug resistance is rendering currently available drugs obsolete. Hence, it is crucial to develop new molecules. Phthalimides, thiosemicarbazones, and 1,3-thiazoles have been used as scaffolds to obtain antiplasmodial and anti-Trypanosoma cruzi agents. Herein we present the synthesis of 24 phthalimido-thiosemicarbazones (3 a-x) and 14 phthalimido-thiazoles (4 a-n) and the corresponding biological activity against T. cruzi, Plasmodium falciparum, and cytotoxicity against mammalian cell lines. Some of these compounds showed potent inhibition of T. cruzi at low cytotoxic concentrations in RAW 264.7 cells. The most active compounds, 3 t (IC =3.60 μM), 3 h (IC =3.75 μM), and 4 j (IC =4.48 μM), were more active than the control drug benznidazole (IC =14.6 μM). Overall, the phthalimido-thiosemicarbazone derivatives were more potent than phthalimido-thiazole derivatives against T. cruzi. Flow cytometry assay data showed that compound 4 j was able to induce necrosis and apoptosis in trypomastigotes. Analysis by scanning electron microscopy showed that T. cruzi trypomastigote cells treated with compounds 3 h, 3 t, and 4 j at IC concentrations promoted changes in the shape, flagella, and surface of the parasite body similar to those observed in benznidazole-treated cells. The compounds with the highest antimalarial activity were the phthalimido-thiazoles 4 l (IC =1.2 μM), 4 m (IC =1.7 μM), and 4 n (IC =2.4 μM). Together, these data revealed that phthalimido derivatives possess a dual antiparasitic profile with potential effects against T. cruzi and lead-like characteristics.
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http://dx.doi.org/10.1002/cmdc.202000331DOI Listing
November 2020

Analysis and spatial distribution of schistosomiasis mansoni in a historically endemic area of northeastern Brazil.

Trop Med Int Health 2020 09 27;25(9):1085-1092. Epub 2020 Jul 27.

Department of Parasitology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil.

Objective: To perform a descriptive analysis of the activities of the Schistosomiasis Control Program, as well as the spatial distribution of the condition in the state of Alagoas, Brazil, for the period from 2007 to 2016.

Methods: Descriptive ecological study. Data from positive human cases and operational data were collected in the Information System of the Schistosomiasis Control Program, and data for spatial analysis were collected on the website of the Brazilian Institute of Geography and Statistics. An analysis of spatial autocorrelation (Moran statistics) was performed, where a spatial pattern was established, which showed the Q1 and Q2 patterns to be the most important, and Q3 and Q4 representing transition areas.

Results: In the years under study, at least 85% (n = 60/70) of the municipalities carried out the activities recommended by the PCE (Schistosomiasis Control Program). Alagoas presented an average positivity rate of 7.1%, which is very high compared to the prevalence of 3.3% at the last national schistosomiasis survey conducted between 2010 and 2015. Moran's statistics showed 22/70 municipalities forming a Q1 cluster, of high/high pattern, and 32/70 municipalities forming a Q2 cluster, of low/low pattern, with the others in a transition area. Moran Map data, however, showed only 7/70 municipalities in the endemic area with a spatial autocorrelation, with these municipalities having the Mundau River as a common element.

Conclusion: Schistosomiasis mansoni is of great importance for public health in Alagoas and that the use of spatial analysis can identify priority areas for preventive and control measures against schistosomiasis mansoni.
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http://dx.doi.org/10.1111/tmi.13458DOI Listing
September 2020

Anti-biofilm effect by the combined action of fluconazole and acetylsalicylic acid against species of Candida parapsilosis complex.

Infect Genet Evol 2020 10 26;84:104378. Epub 2020 May 26.

Departamento de Micologia, Universidade Federal de Pernambuco, Brazil.

The Candida parapsilosis complex has been associated with highly refractory infections mainly due to the presence of biofilms. High glucose levels enable the development of this virulence factor which can aggravate the clinical condition of patients with diabetes mellitus, those using parenteral nutrition, with invasive medical device, including others. Combined antifungal therapy, such as azole and cyclooxygenase inhibitors, may be an alternative in such infections since they modulate prostaglandin production favoring the adhesion and development of biofilms. Thus, the present study aimed to evaluate the influence of glucose supplementation in the formation and detection of Candida parapsilosis complex biofilms and to treat them using fluconazole and a cyclooxygenase inhibitor in combination. Protein spectra evaluation allowed the differentiation between species from the complex (score > 2) in our studies. All isolates were able to form active biofilms at different glucose concentrations. In addition, a significant reduction in biofilm formation was observed when fluconazole and acetylsalicylic acid were combined. The ultrastructural analysis presented typical biofilm characteristics by species from the complex. These data support new combined therapies for the treatment of fungal infections, especially with those which are resistant and therapeutic failure is associated with virulence factors.
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http://dx.doi.org/10.1016/j.meegid.2020.104378DOI Listing
October 2020

Thiophene-thiosemicarbazone derivative (L10) exerts antifungal activity mediated by oxidative stress and apoptosis in C. albicans.

Chem Biol Interact 2020 Apr 28;320:109028. Epub 2020 Feb 28.

Laboratory of Synthesis and Drug Delivery, State University of Paraiba, 58071-160, Brazil.

Reactive oxygen species (ROS) cause cell damage and death. To reverse these effects, cells produce substances such as reduced glutathione (GSH) that serve as substrates for antioxidant enzymes. One way to combat microbial resistance includes nullifying the effect of glutathione in microbial cells, causing them to die from oxidative stress. The compound 2-((5-nitrothiophen-2-yl)methylene)-N-(pyridin-3-yl) hydrazine carbothioamide (L10) is a new thiophene-thiosemicarbazone derivative with promising antifungal activity. The aim of this study was to evaluate its mechanism of action against Candida albicans using assays that evaluate its effects on redox balance. Treatment with L10 promoted significant changes in the minimum inhibitory concentration (MIC) values in ascorbic acid and GSH protection tests, the latter increasing up to 64-fold of the MIC. Using nuclear magnetic resonance, we demonstrated interaction of L10 and GSH. At concentrations of 4.0 and 8.0 μg/mL, significant changes were observed in ROS production and mitochondrial membrane potential. The cell death profile showed characteristics of initial apoptosis at inhibitory concentrations (4.0 μg/mL). Transmission electron microscopy data corroborated these results and indicated signs of apoptosis, damage to plasma and nuclear membranes, and to mitochondria. Taken together, these results suggest a possible mechanism of action for L10 antifungal activity, involving changes in cellular redox balance, ROS production, and apoptosis-compatible cellular changes.
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http://dx.doi.org/10.1016/j.cbi.2020.109028DOI Listing
April 2020

In vitro and in vivo activities of multi-target phtalimido-thiazoles on Schistosomiasis mansoni.

Eur J Pharm Sci 2020 Apr 10;146:105236. Epub 2020 Feb 10.

Laboratório de Imunopatologia e Biologia Molecular IAM/FIOCRUZ, Recife, PE, Brazil. Electronic address:

Schistosomicidal activity of six phthalimido-thiazoles derivatives with substitutions at the position three of the thiazole ring were analyzed in an experimental model. The substituents biphenyl (2i) and 2- naphthyl (2j) at a concentration of 80 µg/mL caused 100% mortality of the parasite in culture after 24 h and 48 h respectively. An evaluation of ultrastructural parasites showed damage in the tegument, formation of bubbles and partial destruction of the tubercles. The in vivo anti-parasitic activity with the derivate 2i was performed by administering it orally and intraperitoneally in a 400 mg/kg/5days regimen. Decreases in the number of eggs in the gut (45.1%) and a reduction of the percentage of mature (23.7%) and increased unviable (53.8%) eggs were observed. Our results also showed a reduction in the number of recovered worms after treatment with 2i (oral administration: 81, 25%). The results demonstrated that the prototypes which were tested had a significant anti-schistosomal effect against S. mansoni, suggesting that these derivatives are promising candidates for further research into the chemotherapy of schistosomiasis.
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http://dx.doi.org/10.1016/j.ejps.2020.105236DOI Listing
April 2020

Investigation of defense response and immune priming in Biomphalaria glabrata and Biomphalaria straminea, two species with different susceptibility to Schistosoma mansoni.

Parasitol Res 2020 Jan 10;119(1):189-201. Epub 2019 Dec 10.

Aggeu Magalhães Institute - FIOCRUZ Pernambuco, Professor Moraes Rego Avenue, s/n - Campus da UFPE - Cidade Universitária, Recife/PE, 50740-465, Brazil.

For many years, the immune response of invertebrates was considered to lack any mechanism of memory. However, the study of their response has shown a kind of acquired immunity, which is not so well understood given the lack of knowledge of the invertebrate defense system. This event can be called "innate immune memory." Recent studies using Biomphalaria glabrata snails have reported this phenomenon, relating it to an increase in humoral products, but no focus was given to hemocyte response or to other species of snails. In this study, we focus on hemocyte dynamics and some humoral factors in the species B. glabrata and B. straminea, the most widespread species in Brazil, sensitized and non-sensitized to the Schistosoma mansoni worm. We report a change in the prevalent hemocyte type after sensitization, through an increase in the proportion of granulocytes, as well as a change in the total number of hemocytes caused by a second exposure to the parasite. We also showed that melanization is not a key factor in Biomphalaria snail defense and varies little after the second exposure event. The data reported in this article confirm the effect of immune priming on these snails and suggest that the increase of humoral products shown in the literature is accompanied by variation in hemocytes after sensitization.
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http://dx.doi.org/10.1007/s00436-019-06495-4DOI Listing
January 2020

Novel indol-3-yl-thiosemicarbazone derivatives: Obtaining, evaluation of in vitro leishmanicidal activity and ultrastructural studies.

Chem Biol Interact 2020 Jan 15;315:108899. Epub 2019 Nov 15.

Universidade Federal de Pernambuco (UFPE), Departamento de Antibióticos, 50670-901, Recife, PE, Brazil. Electronic address:

Parasitic diseases still represent serious public health problems, since the high and steady emergence of resistant strains is evident. Because parasitic infections are distributed predominantly in developing countries, less toxic, more efficient, safer and more accessible drugs have become desirable in the treatment of the infected population. This is the case of leishmaniasis, an infectious disease caused by a protozoan of the genus Leishmania sp., responsible for triggering pathological processes from the simplest to the most severe forms leading to high rates of morbidity and mortality throughout the world. In the search for new leishmanicidal drugs, the thiosemicarbazones and the indole fragments have been identified as promising structures for leishmanicidal activity. The present study proposes the synthesis and structural characterization of new indole-thiosemicarbazone derivatives (2a-j), in addition to performing in vitro evaluations through cytotoxicity assays using macrophages (J774) activity against forms of Leishmania infantum and Leishmania amazonensis promastigote as well as ultrastructural analyzes in promastigotes of L. infantum. Results show that the indole-thiosemicarbazone derivatives were obtained with yield values varying from 32.09 to 94.64%. In the evaluation of cytotoxicity, the indole-thiosemicarbazone compounds presented CC values between 53.23 and 357.97 μM. Concerning the evaluation against L. amazonensis promastigote forms, IC values ranged between 12.31 and  > 481.52 μM, while the activity against L. infantum promastigotes obtained IC values between 4.36 and 23.35 μM. The compounds 2d and 2i tested against L. infantum were the most promising in the series, as they showed the lowest IC values: 5.60 and 4.36 respectively. The parasites treated with the compounds 2d and 2i showed several structural alterations, such as shrinkage of the cell body, shortening and loss of the flagellum, intense mitochondrial swelling and vacuolization of the cytoplasm leading the parasite to cellular unviability. Therefore, the indole-thiosemicarbazone compounds are promising because they yield considerable synthesis, have low cytotoxicity to mammalian cells and act as leishmanicidal agents.
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http://dx.doi.org/10.1016/j.cbi.2019.108899DOI Listing
January 2020

Use of MALDI-TOF MS to identify the culturable midgut microbiota of laboratory and wild mosquitoes.

Acta Trop 2019 Dec 13;200:105174. Epub 2019 Sep 13.

Departamento de Parasitologia, Instituto Aggeu Magalhães (IAM), Fundação Oswaldo Cruz (Fiocruz-Pernambuco), Av. Prof. Moraes Rego s/n, Cidade Universitária, Recife, PE, 50670-420, Brazil; Laboratório de Imunopatologia Keiso Asami (LIKA), Universidade Federal de Pernambuco (UFPE), Av. Prof. Moraes Rego s/n - Cidade Universitária, Recife, PE, 52171-011, Brazil. Electronic address:

Mosquitoes are responsible for transmitting many pathogens to humans and Aedes aegypti, Aedes albopictus and Culex quinquefasciatus are important vectors in the world. The microbiota plays an important role in developmental studies that involve impacts on the biological cycle of mosquitoes and vector control strategies. In this study, the aim was to understand the environment plays in the microbiota culturable diversity of Aedes aegytpi, Aedes albopictus and Culex quinquefasciatus. Midgut of studied mosquitoes (laboratory-reared and wild) were dissected and analyzed by MALDI-TOF MS to identify the microbiota. Most of the bacteria identified in the microbiota of mosquitoes from the laboratory and field belong to the phylum Proteobacteria. We reported on the microbial diversity among the mosquito species studied where Cx. quinquefasciatus and Ae. albopictus show greater bacterial similarity. The genus Rahnella was present in all mosquito species studied, both in those from the laboratory and those from the wild. Bacillus, Ewingella, Microccocus, Klebsiella and Pantoea are genera was predominant among the mosquitoes studied. The difference of microbiota diversity between mosquitoes laboratory-reared and wild shows that the environment plays an important role in the acquisition of bacteria, mainly in Ae. aegypti and Cx. quinquefasciatus.
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http://dx.doi.org/10.1016/j.actatropica.2019.105174DOI Listing
December 2019

Phenotypic, structural, and ultrastructural analysis of triple-negative breast cancer cell lines and breast cancer stem cell subpopulation.

Eur Biophys J 2019 Oct 4;48(7):673-684. Epub 2019 Sep 4.

Serviço de Biologia Celular, Diretoria de Pesquisa e Desenvolvimento, Fundação Ezequiel Dias, Rua Conde Pereira Carneiro 80, Gameleira, Belo Horizonte, Minas Gerais, 30510-010, Brazil.

Triple negative breast cancer (TNBC) is a highly heterogeneous disease, which influences the therapeutic response and makes difficult the discovery of effective targets. This heterogeneity is attributed to the presence of breast cancer stem cells (BCSCs), which determines resistance to chemotherapy and subsequently disease recurrence and metastasis. In this context, this work aimed to evaluate the morphological and phenotypic cellular heterogeneity of two TNBC cell lines cultured in monolayer and tumorsphere (TS) models by fluorescence and electron microscopy and flow cytometry. The BT-549 and Hs 578T analyses demonstrated large phenotypic and morphological heterogeneity between these cell lines, as well as between the cell subpopulations that compose them. BT-549 and Hs 578T are heterogeneous considering the cell surface marker CD44 and CD24 expression, characterizing BCSC mesenchymal-like cells (CD44/CD24), epithelial cells (CD44/CD24), hybrid cells with mesenchymal and epithelial features (CD44/CD24), and CD44/CD24 cells. BCSC epithelial-like cells (ALDH) were found in BT-549, BT-549 TS, and Hs 578T TS; however, only BT-549 TS showed a high ALDH activity. Ultrastructural characterization showed the heterogeneity within and among BT-549 and Hs 578T in monolayer and TS models being formed by more than one cellular type. Further, the mesenchymal characteristic of these cells is demonstrated by E-cadherin absence and filopodia. It is well known that tumor cell heterogeneity can influence survival, therapy responses, and the rate of tumor growth. Thus, molecular understanding of this heterogeneity is essential for the identification of potential therapeutic options and vulnerabilities of oncological patients.
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http://dx.doi.org/10.1007/s00249-019-01393-0DOI Listing
October 2019

In vitro activity, ultrastructural studies and in silico pharmacokinetic properties of indol-3-yl-thiosemicarbazones derivatives and analogues against juvenile and adult worms of S. mansoni.

Eur J Pharm Sci 2019 Oct 5;138:104985. Epub 2019 Jul 5.

Universidade Federal de Pernambuco (UFPE), Departamento de Antibióticos, 50670-901 Recife, PE, Brazil. Electronic address:

The present work aimed to carry out in vitro biological assays of indol-3-yl derivatives thiosemicarbazones (2a-e) and 4-thiazolidinones (3a-d) against juvenile and adult worms of S. mansoni, as well as the in silico determination of pharmacokinetic parameters for the prediction of the oral bioavailability of these derivatives. All compounds were initially screened at a concentration of 200 μM against S. mansoni adult worms and the results evidenced the good activity of compounds 2b, 2d and 3b, which caused 100% mortality after 24, 48 and 72 h, respectively. Subsequent studies with these same compounds revealed that compound 2b was able to reduce the viability of the parasites by 85% and 83% at concentrations of 200 and 100 μM, respectively. In relation to the juvenile worms, all compounds (2b, 2d and 3b) were able to cause mortality, but compound 2b demonstrated better activity causing 100% mortality in 48 h. Additionally, it was possible to observe reduction in the viability of juvenile worms of 85%, 81% and 64% at concentrations of 200, 100 and 50 μM, respectively. Several ultrastructural damages were observed when adult and juvenile S. mansoni worms were exposed to compound 2b (200 μM) that was characterized by extensive destruction by the integument, which may justify the mortality rate of cultured parasites. In the DNA interaction assay, fragmentation of the genetic material of adult worms when treated with compound 2b (200 μM) was evidenced, indicating the apoptosis process as mechanism of parasite death. Regarding pharmacokinetic properties, all derivatives are according to the required parameters, predicting good oral bioavailability for the studied compounds. The results presented in this study reveal the good activity of compound 2b in both adult and juvenile worms of S. mansoni, pointing this compound as promising in the development of further studies on schistosomicidal activity.
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http://dx.doi.org/10.1016/j.ejps.2019.104985DOI Listing
October 2019

Punica granatum sarcotesta lectin (PgTeL) has antibacterial activity and synergistic effects with antibiotics against β-lactamase-producing Escherichia coli.

Int J Biol Macromol 2019 Aug 3;135:931-939. Epub 2019 Jun 3.

Departamento de Bioquímica, Centro de Biociências, Universidade Federal de Pernambuco, Recife, Brazil. Electronic address:

The sarcotesta of Punica granatum fruit contains an antimicrobial lectin called PgTeL. In this work, we evaluated the antibacterial activity of PgTeL against five drug-resistant Escherichia coli isolates able to produce β-lactamases. Minimum inhibitory (MIC) and bactericidal (MBC) concentrations were determined by broth dilution. Morphometric and viability analyses were performed by flow cytometry, and ultrastructural changes were evaluated by scanning electron microscopy. Potential synergistic effects of PgTeL with antibiotics and anti-biofilm effect were also evaluated. PgTeL showed antibacterial activity against all isolates with MIC and MBC values ranging from 12.5 to 50.0 μg/mL and from 25.0 to 100.0 μg/mL, respectively. For most isolates, PgTeL postponed the growth start by at least ten hours. At the MIC, the lectin caused alterations in size, shape and structure of bacterial cells. The combination PgTeL-ceftazidime showed a synergistic effect for all isolates. Synergy was also detected with ampicillin (one isolate), carbenicillin (one isolate), cefotaxime (one isolate), cephalexin (four isolates) and cefuroxime (three isolates). PgTeL exhibited anti-biofilm activity against all isolates, causing ≥50% inhibition of biofilms at or above 6.25 μg/mL. The antibacterial effect of PgTeL and its synergy with antibiotics indicate that this fruit-derived molecule may have potential for future treatment of multidrug-resistant infections.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.06.011DOI Listing
August 2019

Schistosomicidal and prophylactic activities of phthalimido-thiazoles derivatives on schistosomula and adult worms.

Eur J Pharm Sci 2019 May 12;133:15-27. Epub 2019 Mar 12.

Department of Pharmaceutical Sciences, Federal University of Pernambuco, S/N - Campus da UFPE, Recife, PE CEP: 50740-520, Brazil.

Schistosomiasis is a major public health problem worldwide, especially in poor communities. Praziquantel is currently the only drug available to treat schistosomiasis and it shows low efficacy against schistosomula and juveniles stages of Schistosoma mansoni, allowing lower cure rate in areas with high endemicity. There is an urgent need to identify new antischistosomal drugs. Previous works identified phthalimido-thiazoles as privileged structures acting as schistossomicidal agent. In this way, a phthalimido-thiosemicarbazide intermediate and eight phthalimido-thiazoles derivatives were evaluated concerning the in vitro antischistosomal activity compounds in adult phase of Schistosoma mansoni and examined alterations on the tegumental surface. The results revealed that compounds 2f, 2 l and 2 m caused significant mortality in adult worms at concentrations range of 20 μg/mL to 100 μg/mL. These compounds were also selected in view to verify the activity against the schistosomula. Compound 2 m promoted 100% of mortality of larval forms until doses of 2.5 μg/mL within 48 h. In addition, when compound 2 m was administered orally at dose of 200 mg/kg for 5 consecutive days to the infected mouse with adult schistosomes, a reduction in the parasite burden was observed. Furthermore, scanning electron microscopy revealed that compound 2 m kill the parasite by tegumental damage and bubbles generation.
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http://dx.doi.org/10.1016/j.ejps.2019.03.008DOI Listing
May 2019

Comparative anatomy and histochemistry of the leaf blade of two species of Artocarpus.

An Acad Bras Cienc 2019 Feb 14;91(1):e20170922. Epub 2019 Feb 14.

Laboratório de Farmacognosia, Departamento de Ciências Farmacêuticas, Universidade Federal de Pernambuco, Av. Prof. Arthur de Sá, s/n, Cidade Universitária, 50740-521 Recife, PE, Brazil.

In Brazil, there are two species of Artocarpus that were introduced: Artocarpus altilis (Parkinson) Fosberg, known as fruta-pão, and Artocarpus heterophyllus Lam., known as jaca. Both are used as food and medicine. The objective of this work was to conduct a comparative anatomical and histochemical study between A. altilis and A. heterophyllus. Techniques of optical, polarized and scanning electron coupled to energy dispersive spectroscopy. The anatomical characterization showed the characters of general occurrence in the family Moraceae and of those that allow the differentiation of A. altilis and A. heterophyllus. The histochemistry revealed the sites of synthesis and/or storage of the metabolites. The chemical microanalyses brought new information about the chemical composition of crystals. The study provides pharmacobotanical data for the quality control of the species.
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http://dx.doi.org/10.1590/0001-3765201820170922DOI Listing
February 2019

First detection of a allele V1016G conferring a high level of insecticide resistance in collected from Europe (Italy) and Asia (Vietnam), 2016: a new emerging threat to controlling arboviral diseases.

Euro Surveill 2019 Jan;24(5)

Department of Medical Entomology, National Institute of Infectious Diseases, Tokyo, Japan.

Introduction (Skuse) is an important vector of arboviral diseases, including dengue, chikungunya and Zika virus disease. Monitoring insecticide resistance and mechanisms by which the mosquito develops resistance is crucial to minimise disease transmission.AimTo determine insecticide resistance status and mechanisms in from different geographical regions.MethodsWe sampled 33 populations of from Asia, Europe and South America, and tested these for susceptibility to permethrin, a pyrethroid insecticide. In resistant populations, the target site for pyrethroids, a voltage-sensitive sodium channel () was genotyped. Three resistant sub-strains, each harbouring a resistance allele homozygously, were established and susceptibilities to three different pyrethroids (with and without a cytochrome P450 inhibitor) were assayed.ResultsMost populations of tested were highly susceptible to permethrin but a few from Italy and Vietnam (4/33), exhibited high-level resistance. Genotyping studies detected a knockdown resistance () allele V1016G in for the first time in . Two previously reported alleles, F1534C and F1534S, were also detected. The bioassays indicated that the strain homozygous for the V1016G allele showed much greater levels of pyrethroid resistance than other strains harbouring F1534C or F1534S.ConclusionThe V1016G allele was detected in bothAsian and Italian populations, thus a spread of this allele beyond Italy in Europe cannot be ruled out. This study emphasises the necessity to frequently and regularly monitor the V1016G allele in , particularly where this mosquito species is the main vector of arboviruses.
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http://dx.doi.org/10.2807/1560-7917.ES.2019.24.5.1700847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386213PMC
January 2019

Invasive Candida tropicalis Infection Caused by Catheter Biofilm in a Patient with Tongue Cancer.

Mycopathologia 2019 Apr 1;184(2):345-346. Epub 2019 Feb 1.

Departamento de Micologia, Universidade Federal de Pernambuco (UFPE), Av. da engenharia S/N, Recife, Pernambuco, 50740-600, Brazil.

Systemic infections due to Candida tropicalis are conditions which can frequently lead to death. The aim of this report is to describe the features of C. tropicalis biofilm in a patient with catheter-associated fungemia.
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http://dx.doi.org/10.1007/s11046-018-0316-zDOI Listing
April 2019

Immunological Parameters of the Pomacea lineata Spix, 1827 (Mollusca: Caenogastropoda) Exposed to Schistosoma mansoni Sambon, 1907.

Acta Parasitol 2019 Mar 22;64(1):31-43. Epub 2019 Jan 22.

Department of Animal Morphology and Physiology, Federal Rural University of Pernambuco, UFRPE-DMFA, Av. Dom Manoel de Medeiros s/n Dois, s/n, Dois Irmãos District, Recife, PE, 52171-900, Brazil.

Introduction: Pomacea lineata acts as the natural biological controller of Biomphalaria glabrata, the intermediate host of Schistosoma mansoni, as they are found in the same environment. However, there are no studies reporting an infection in P. lineata due to S. mansoni. Thus, this work investigated parameters related to the immunity of P. lineata after exposure for 24 and 48 h to S. mansoni under experimental conditions.

Methods: The F1 generation of these snails was used in this study. The total and differential counts of hemocytes, phenoloxidase, nitric oxide, total proteins, expression of TNF-α in hemocytes and histopathology of the head-foot organ were analyzed.

Results: Exposure to S. mansoni promoted an increase in the total number of hemocytes, an increase of granulocytes, a reduction of agranulocytes and hyalinocytes, an increase in phenoloxidase levels, total proteins and nitric oxide. There was TNF-α expression in the agranulocytes and granulocytes, increasing in intensity after exposure to the trematode. Head-foot histopathology revealed the presence of sporocytes in the fibromuscular layer surrounded by granulation tissue only within 24 h. At 48 h, there was marked fibrosis in this layer and little granulation tissue.

Conclusion: Thus, we can conclude that P. lineata seems to trigger a series of immunological strategies in a very effective way that confers some resistance to S. mansoni.
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http://dx.doi.org/10.2478/s11686-018-00005-9DOI Listing
March 2019

In vitro evaluation of mercury (Hg) effects on biofilm formation by clinical and environmental isolates of Klebsiella pneumoniae.

Ecotoxicol Environ Saf 2019 Mar 27;169:669-677. Epub 2018 Nov 27.

Departamento de Bioquímica, Centro de Biociências, Universidade Federal de Pernambuco, Pernambuco, Brazil. Electronic address:

The increase in urbanization and industrialization has contributed to the contamination of different environments by means of xenobiotic compounds, such as heavy metals, causing changes in microbial communities. Among these metals, the Mercury (Hg) is one the most prevalent toxic metals for the environment The present study aimed to evaluate the effect of mercury on the formation of biofilm by environmental (collected from urban stream water) and clinical isolates of Klebsiella pneumoniae. In addition, antibiotic resistance, virulence factors, and genetic diversity were investigated. Taxonomic identity of eight isolates (one reference, two clinical, and five environmental isolates) was performed by MALDI-TOF-MS, while the antibiotic susceptibility profile was assessed by the disc diffusion method. The ability to form biofilms was evaluated by culture on Congo red agar and by crystal violet staining. Biofilm structure was analyzed by scanning electron microscopy. The hydrophobicity profile and the presence of the virulence genes cps, fimH, and mrkD was investigated. The presence of merA and its relationship with antimicrobial resistance were also assessed. The identity of all isolates was confirmed by MALDI-TOF-MS, and different profiles of resistance to mercury and antibiotics as well as of biofilm formation were identified for the clinical and environmental isolates. All isolates were hydrophilic and positive for the virulence genes cps, fimH, and mrkD; only the clinical isolate K36-A2 was positive for merA. The diversity of the isolates was confirmed by ERIC-PCR, which revealed high heterogeneity among the isolates. In conclusion, the data demonstrate that the investigated isolates present different responses to exposure to Hg and correspond to distinct populations of K. pneumoniae disseminated in the investigated environment. The data obtained in this work will aid in understanding the mechanisms of survival of this pathogen under adverse conditions.
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http://dx.doi.org/10.1016/j.ecoenv.2018.11.036DOI Listing
March 2019

Punica granatum sarcotesta lectin (PgTeL) impairs growth, structure, viability, aggregation, and biofilm formation ability of Staphylococcus aureus clinical isolates.

Int J Biol Macromol 2019 Feb 7;123:600-608. Epub 2018 Nov 7.

Departamento de Bioquímica, Centro de Biociências, Universidade Federal de Pernambuco, Recife, Brazil. Electronic address:

In this work, we evaluated the ability of Punica granatum sarcotesta lectin (PgTeL) to impair the growth and viability of the Staphylococcus aureus clinical isolates 8325-4 (non-resistant) and LAC USA300 (MRSA strain). The effects of this lectin on aggregating, hemolytic activity, biofilm-forming ability, and expression of virulence genes (hla, rnaIII, and spa) were also investigated. PgTeL showed antibacterial activity against 8325-4 and LAC USA300 strains by interfering with both the growth (MIC of 6.25 and 12.5 μg/mL, respectively) and survival (MBC values of 25.0 and 50.0 μg/mL, respectively). Culture growth started only at the ninth (8325-4) and tenth (LAC USA300) hour in the presence of PgTeL at MIC, while growth was detected since the first hour in the control. The lectin caused markedly altered cell morphology in both the strains. Although, at the MIC, PgTeL caused structural alterations, most cells were still viable, while at the MBC it promoted cell injury and death. PgTeL showed anti-aggregation effect and exhibited antibiofilm activity against both the isolates. However, the lectin did not interfere with the hemolytic activity of LAC USA300 and with the expression of hla, rnaIII, and spa genes. In conclusion, PgTeL is a lectin with multiple inhibitory effects on S. aureus clinical isolates.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.11.030DOI Listing
February 2019

Social determinants of health associated with topical repellent use in pregnancy: a cross-sectional study during a Zika outbreak in Brazil.

Trans R Soc Trop Med Hyg 2019 02;113(2):65-73

Laboratório de Imunopatologia Keizo Asami, Universidade Federal de Pernambuco, Recife, CEP, Brazil.

Background: Repellent use during pregnancy was strongly recommended after uncovering Zika virus (ZIKV) involvement with congenital malformations. In this context, Pernambuco, Brazil played a key role since it was the epicentre for the main studies suggesting ZIKV teratogenicity and one of Brazil's most affected states during the 2014-2016 epidemics. Thus we aimed to identify possible associations between social determinants of health and repellent use in pregnancy during the ZIKV outbreak in Pernambuco.

Methods: We conducted a cross-sectional study (July-December 2016) with 539 pregnant women residing in Pernambuco and estimated the associations by prevalence ratio and multivariable logistic regression.

Results: Repellents were associated with pregnant women ≥30 y; graduates, employed, health professionals, private health system users and with a monthly income per person greater than two minimum wages. Women whose domiciles favour mosquitoes (ground-floor houses, intermittent water supply from general distribution or water trucks and for ≤6 d/week, cesspools/open wastewater, indoor household water storage) were less likely to use repellents. There was no association for peridomiciles.

Conclusions: Repellents were not associated with ZIKV in most vulnerable pregnant women, despite all the general recommendations made during the Pernambuco epidemic. This study observed a demand for public policies focused on health, education and sanitation problems related to deprived social groups along with their co-responsibility rather than focusing on individual attitudes against mosquitoes.
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http://dx.doi.org/10.1093/trstmh/try114DOI Listing
February 2019

Phthalimido-thiazole as privileged scaffold: activity against immature and adult worms of Schistosoma mansoni.

Parasitol Res 2018 Jul 7;117(7):2105-2115. Epub 2018 May 7.

Department of Pharmaceutical Sciences, Federal University of Pernambuco, S/N-Campus da UFPE, Recife, PE, CEP: 50740-520, Brazil.

Phthalimide, 1,3-thiazole, and thiazolidinone cores are considered privileged scaffolds and represent an attractive starting point to design new bioactive compounds for neglected tropical disease (NTD). Schistosomiasis is a NTD, caused by Schistosoma worms which praziquantel (PZQ) is the only drug used to treat humans, but the decrease in the effect after treatment has been reported. Recently, some phthalimide-thiazole derivatives exhibited in vitro antischistosomal activity against adult worms with significant ultrastructural changes and a lower cytotoxic effect on splenocytes. This new biological phthalimido-thiazole profile has motivated us to evaluate a new generation of such molecules in immature and adult worms. Thus, a phthalimido-thiazolidinone derivative, (3c), and three phthalimido-thiazoles (6c, 7a, and 7h) were evaluated concerning their in vitro activity on schistosomulae and adult worms. The results showed that these compounds brought a significant reduction on the mortality, inhibited oviposition, and then induced mortality in immature and adult worms alike. According to scanning electron microscopy, the tegument was the principal target for 7a and 7h and revealed gradual damage to the tegument surface, inducing destruction and decomposition of the tegument in the same areas and exposition of subtegumental tissue and of muscle tissue. Furthermore, they caused less toxicity in splenocytes than PZQ. Compounds 7a and 7h revealed to possess promising activity against larval forms. According to the present study, the privileged structure phthalimido-thiazoles act as a molecular framework that has antischistosomal activity and most form the basis to the next pre-clinical tests. Graphical abstract.
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http://dx.doi.org/10.1007/s00436-018-5897-4DOI Listing
July 2018
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