Saturated Iso-Type Fatty Acids from the Marine Bacterium Mesoflavibacter zeaxanthinifaciens with Anti-Trypanosomal Potential.

Chagas disease is a Neglected Tropical Disease with limited and ineffective therapy. In a search for new anti-trypanosomal compounds, we investigated the potential of the metabolites from the bacteria living in the corals and sediments of the southeastern Brazilian coast. Three corals, Tubastraea coccinea, Mussismilia hispida, Madracis decactis, and sediments yielded 11 bacterial strains that were fully identified by MALDI-ToF/MS or gene sequencing, resulting in six genera-Vibrio, Shewanella, Mesoflavibacter, Halomonas, Bacillus, and Alteromonas. To conduct this study, EtOAc extracts were prepared and tested against Trypanosoma cruzi. The crude extracts showed IC50 values ranging from 15 to 51 µg/mL against the trypomastigotes. The bacterium Mesoflavibacter zeaxanthinifaciens was selected for fractionation, resulting in an active fraction (FII) with IC50 values of 17.7 µg/mL and 23.8 µg/mL against the trypomastigotes and amastigotes, respectively, with neither mammalian cytotoxicity nor hemolytic activity. Using an NMR and ESI-HRMS analysis, the FII revealed the presence of unsaturated iso-type fatty acids. Its lethal action was investigated, leading to a protein spectral profile of the parasite altered after treatment. The FII also induced a rapid permeabilization of the plasma membrane of the parasite, leading to cell death. These findings demonstrate that these unsaturated iso-type fatty acids are possible new hits against T. cruzi.

Avaliação de risco agudo à exposição dietética a resíduos de agrotóxicos em tomate / Acute risk assessment of dietary exposure to pesticide residues in tomato

A utilização de agrotóxicos ao redor do mundo é elevada, estimada em mais 2 milhões de toneladas e somente o continente americano emprega 1,2 milhão de toneladas de produtos. O Brasil possui na agricultura a sua principal atividade econômica e utilizou em 2021 aproximadamente 700 mil toneladas de agrotóxicos. O tomate é um dos vegetais mais cultivados e consumidos no mundo e o Brasil figura como o 10º maior produtor. O consumo anual médio de tomate do brasileiro é de 4,2 kg, é um vegetal nutritivo e com propriedades associadas à prevenção de câncer. O tomate é uma das culturas com maior uso de agrotóxicos e durante o período desse estudo, era autorizado o uso de 123 agrotóxicos. Os resíduos desses produtos nos alimentos podem acarretar em diversos problemas à saúde, mesmo em curta exposição (< 24h). Desse modo, uma das maneiras de garantir a segurança alimentar da população é a realização da avaliação de risco de contaminação dietética. No processo de validação 73 ingredientes ativos respeitaram os critérios do protocolo adotado. Para a realização da estimativa de risco de exposição dietética aguda, foram coletadas 30 amostras de tomate in natura e 11 de tomate pelado, entre setembro de 2021 e março de 2022. Para a extração dos compostos de interesse foi utilizado o método QuEChERS e para avaliação dos resíduos, a cromatografia líquida acoplada à espectrometria de massas. Das amostras de tomate in natura, somente seis (20 %) estavam isentas dos compostos pesquisados; 18 (60 %) apresentaram resíduo(s) abaixo do limite (LMR) estabelecido e seis amostras (20 %) foram consideradas impróprias ao consumo. Das amostras de tomate pelado, três estavam isentas dos agrotóxicos pesquisados e oito (72 %) apresentaram resíduo de carbendazim abaixo do LMR. Nenhuma das amostras mostrou potencial de contaminação aguda por agrotóxicos, apesar disso não é possível afirmar que não há risco, pois não há como estimar os potenciais efeitos adversos provenientes do consumo de um alimento com múltiplos compostos.

More than 2 million tons of pesticide products are used annually through the world and only the America continent was used 1,2 million tons of these products. The agriculture is the main economic activity in Brazil, this way in 2021 approximately 700 thousand tons of pesticide were applied in its crops. Tomato is one of the most cultivated and consumed vegetables in the world and Brazil is the 10th largest producer. The Brazilian people consumes an average of 4.2 kg of tomatoes by year, it is a nutritious vegetable with anti-cancer properties. Tomato crop is one of the which highest pesticide usages, during this study 123 compounds were permitted for this crop. Pesticide residues in food may causes several health problems, even in short-term exposition (< 24h), thus one of the ways to ensure the food safety to population is performing the dietary contamination risk assessment. In the validation process 73 active ingredients were within the established criteria. To perform the acute risk assessment of dietary exposure, were collected samples of: fresh tomato (30) and whole peeled tomato (11) in between September of 2021 and March of 2022. To extraction of interest substances was used the QuEChERS method and to residue evaluation the liquid chromatography coupled to mass spectrometry. Of the fresh tomato samples, only six (20 %) were free of searched analytes; 18 (60 %) showed residue(s) bellow the established limits (MRL) and six (20 %) were considered unfit to consumption. Of the whole peeled tomato samples, three were free of searched substances and eight (72 %) showed residue of carbendazim bellow the MRL. None of the samples showed potential for acute contamination by pesticide, however it is not possible to say that there is no risk, as there is no way to estimate the potential adverse effects on health arising from the consumption of a food with several compounds.

A new reduced chalcone-derivative affects the membrane permeability and electric potential of multidrug-resistant Enterococcusfaecalis.

The emergence and spread of multidrug-resistant (MDR) enterococci and other Gram-positive bacteria represents a severe problem due to the lack of effective therapeutic alternatives. Natural products have long been an important source of new antibacterial scaffolds and can play a key role in the current antibiotic crisis. Enterococci are predominantly non-pathogenic gastrointestinal commensal bacteria, but among them, Enterococcus faecalis and Enterococcus faecium represent the species that account for most clinically relevant infections. The emergence of MDR enterococci has reduced the available antibiotic treatment options and highlights the need to develop new antimicrobial compounds. In the search for new hit compounds against MDR Enterococcus spp., natural-derived compounds represent inspiring scaffolds for drug design studies. In this work, the antimicrobial activity of a fully synthetic chalcone derivative (r4MB) was determined on a clinical panel of 34 MDR Gram-positive bacteria, mostly constituted by E. faecalis and E. faecium, along with Staphylococcus spp., amongst others. Compound r4MB showed activity against 100% of the tested strains, with the minimum inhibitory concentration (MIC) in the range of 5-20 µM. The lethal action of the compound was evaluated using different fluorescent-based assays. The compound showed a time-dependent permeabilisation of the membrane of a vancomycin-resistant E. faecalis, detected by the fluorescent probe SYTOX Green, and digital fluorescent microscopy corroborated the spectrofluorimetric analysis within 6 min of incubation. Flow cytometry analysis of the membrane electric potential demonstrated a significant depolarization, confirming the target of the compound towards the bacterial membrane. No cytotoxic haemolysis was observed with mammalian erythrocytes, and a 99% cytotoxic concentration of 118 µM on NCTC cells demonstrated a promising antimicrobial selectivity. In silico studies using SwissADME and ADMETLabs servers suggest that compound r4MB displayed adequate ADME properties, with no alerts for pan-assay interference compounds (PAINS). Future hit-to-lead optimization of this chalcone derivative can contribute to developing a more potent derivative against infections caused by MDR enterococci.