Fiocruz in Antarctica - health and environmental surveillance facing the challenges of the 21st century.

FioAntar, FIOCRUZ's research project in Antarctica, is based on the One Health approach. FioAntar aims to generate relevant information that will help reduce the risk of future pandemics and improve the search for chemical compounds and new biological molecules. After four expeditions to Antarctica under the scope of PROANTAR, Fiocruz has identified Influenza H11N2 virus in environmental fecal samples, as well as Histoplasma capsulatum and Bacillus cereus in soil samples. In addition, in a prospective virome analysis from different lakes in the South Shetland Islands, six viral orders were described, supporting future research related to the biodiversity and viral ecology in this extreme ecosystem. Our findings of environmental pathogens of public health importance are a warning about the urgency of establishing a surveillance agenda on zoonoses in Antarctica due to the imminent risks that ongoing environmental and climate changes impose on human health across the planet. FioAntar strives to establish a comprehensive surveillance program across Antarctica, monitoring circulation of pathogens with the potential to transcend continent boundaries, thereby mitigating potential spread. For Fiocruz, Antarctica signifies a new frontier, teeming with opportunities to explore novel techniques, refine established methodologies, and cultivate invaluable knowledge.

Aptamer-Based Recognition of Breast Tumor Cells: A New Era for Breast Cancer Diagnosis.

Breast cancer is one of the leading causes of death among women worldwide and can be classified into four major distinct molecular subtypes based on the expression of specific receptors. Despite significant advances, the lack of biomarkers for detailed diagnosis and prognosis remains a major challenge in the field of oncology. This study aimed to identify short single-stranded oligonucleotides known as aptamers to improve breast cancer diagnosis. The Cell-SELEX technique was used to select aptamers specific to the MDA-MB-231 tumor cell line. After selection, five aptamers demonstrated specific recognition for tumor breast cell lines and no binding to non-tumor breast cells. Validation of aptamer specificity revealed recognition of primary and metastatic tumors of all subtypes. In particular, AptaB4 and AptaB5 showed greater recognition of primary tumors and metastatic tissue, respectively. Finally, a computational biology approach was used to identify potential aptamer targets, which indicated that CSKP could interact with AptaB4. These results suggest that aptamers are promising in breast cancer diagnosis and treatment due to their specificity and selectivity.

Active surveillance for influenza virus and coronavirus infection in Antarctic birds and mammals in environmental fecal samples, South Shetland Islands.

Numerous Antarctic species are recognized as reservoirs for various pathogens, and their migratory behavior allows them to reach the Brazilian coast, potentially contributing to the emergence and circulation of new infectious diseases. To address the potential zoonotic risks, we conducted surveillance of influenza A virus (IAV) and coronaviruses (CoVs) in the Antarctic Peninsula, specifically focusing on different bird and mammal species in the region. During the summer of 2021/2022, as part of the Brazilian Antarctic Expedition, we collected and examined a total of 315 fecal samples to target these respiratory viruses. Although we did not detect the viruses of interest during this particular expedition, previous research conducted by our team has shown the presence of the H11N2 subtype of influenza A virus in penguin fecal samples from the same region. Given the continuous emergence of new viral strains worldwide, it is crucial to maintain active surveillance in the area, contributing to strengthening integrated One Health surveillance efforts.

Microbiome and virome on indoor surfaces of an Antarctic research ship

BACKGROUND Few studies have focused on microbial diversity in indoor environments of ships, as well as the role of the microbiome and its ecological interconnections. In this study, we investigated the microbiome and virome present on the internal surfaces of a polar ship in different stages (beginning, during, and at the end) of the Brazilian Antarctic expedition in order to evaluate abundance of microorganisms in different periods. OBJECTIVES AND METHODS We used shotgun metagenomic analysis on pooled samples from sampling surfaces in the ship's interior to track the microbial diversity. FINDINGS Considering the total fraction of the microbiome, the relative abundance of bacteria, eukaryotes, viruses, and archaea was 83.7%, 16.2%, 0.04%, and 0.002%, respectively. Proteobacteria was the most abundant bacterial phyla, followed by Firmicutes, Actinobacteria, and Bacteroidetes. Concerning the virome, the greatest richness of viral species was identified during the middle of the trip, including ten viral families after de novo assembly: Autographiviridae, Chrysoviridae, Genomoviridae, Herelleviridae, Myoviridae, Partitiviridae, Podoviridae, Potyviridae, Siphoviridae, and Virgaviridae. MAIN CONCLUSIONS This study contributed to the knowledge of microbial diversity in naval transportation facilities, and variations in the abundance of microorganisms probably occurred due to factors such as the number of passengers and activities on the ship.

Transforming growth factor-ß as a therapeutic target for the cardiac damage of Chagas disease

Transforming growth factor beta (TGF-β) is deeply involved on the pathogenesis of Chagas disease. Our group has been investigating the participation of this pleiotropic cytokine in different aspects of Chagas disease over the last 20 years. Important observations have been made, such as: (i) the ability of Trypanosoma cruzi in activating latent TGF-β; (ii) the potential involvement of TGF-β pathway on T. cruzi invasion of host cells; (iii) association of TGF-β with parasite intracellular replication; (iv) cardiac fibrosis development and maintenance; (v) disruption of Connexin-43 plaque structures and (vi) inflammation and immune response. In this perspective article we intend to discuss the advances of the potential use of new therapies targeting TGF-β to treat the cardiac alterations of Chagas disease-affected patients.

In vitro and in vivo experimental models for drug screening and development for Chagas disease

Chagas disease, a neglected illness, affects nearly 12-14 million people in endemic areas of Latin America. Although the occurrence of acute cases sharply has declined due to Southern Cone Initiative efforts to control vector transmission, there still remain serious challenges, including the maintenance of sustainable public policies for Chagas disease control and the urgent need for better drugs to treat chagasic patients. Since the introduction of benznidazole and nifurtimox approximately 40 years ago, many natural and synthetic compounds have been assayed against Trypanosoma cruzi, yet only a few compounds have advanced to clinical trials. This reflects, at least in part, the lack of consensus regarding appropriate in vitro and in vivo screening protocols as well as the lack of biomarkers for treating parasitaemia. The development of more effective drugs requires (i) the identification and validation of parasite targets, (ii) compounds to be screened against the targets or the whole parasite and (iii) a panel of minimum standardised procedures to advance leading compounds to clinical trials. This third aim was the topic of the workshop entitled Experimental Models in Drug Screening and Development for Chagas Disease, held in Rio de Janeiro, Brazil, on the 25th and 26th of November 2008 by the Fiocruz Program for Research and Technological Development on Chagas Disease and Drugs for Neglected Diseases Initiative. During the meeting, the minimum steps, requirements and decision gates for the determination of the efficacy of novel drugs for T. cruzi control were evaluated by interdisciplinary experts and an in vitro and in vivo flowchart was designed to serve as a general and standardised protocol for screening potential drugs for the treatment of Chagas disease.

A new approach for potential drug target discovery through in silico metabolic pathway analysis using Trypanosoma cruzi genome information

The current drug options for the treatment of chronic Chagas disease have not been sufficient and high hopes have been placed on the use of genomic data from the human parasite Trypanosoma cruzi to identify new drug targets and develop appropriate treatments for both acute and chronic Chagas disease. However, the lack of a complete assembly of the genomic sequence and the presence of many predicted proteins with unknown or unsure functions has hampered our complete view of the parasite's metabolic pathways. Moreover, pinpointing new drug targets has proven to be more complex than anticipated and has revealed large holes in our understanding of metabolic pathways and their integrated regulation, not only for this parasite, but for many other similar pathogens. Using an in silicocomparative study on pathway annotation and searching for analogous and specific enzymes, we have been able to predict a considerable number of additional enzymatic functions in T. cruzi. Here we focus on the energetic pathways, such as glycolysis, the pentose phosphate shunt, the Krebs cycle and lipid metabolism. We point out many enzymes that are analogous to those of the human host, which could be potential new therapeutic targets.

Inhibition of Trypanosoma cruzi proline racemase affects host-parasite interactions and the outcome of in vitro infection

Proline racemase is an important enzyme of Trypanosoma cruzi and has been shown to be an effective mitogen for B cells, thus contributing to the parasite's immune evasion and persistence in the human host. Recombinant epimastigote parasites overexpressing TcPRAC genes coding for proline racemase present an augmented ability to differentiate into metacyclic infective forms and subsequently penetrate host-cells in vitro. Here we demonstrate that both anti T. cruzi proline racemase antibodies and the specific proline racemase inhibitor pyrrole-2-carboxylic acid significantly affect parasite infection of Vero cells in vitro. This inhibitor also hampers T. cruzi intracellular differentiation.

Comparando genomas: bancos de dados e ferramentas computacionais para a análise comparativa de genomas procarióticos / Comparing genomes: databases and computational tools for comparative analysis of prokaryotic genomes

Desde a década de 1990, os esforços internacionais no sentido de obter seqüências genômicas completas levaram à determinação de todo o código genético de mais de 600 organismos, entre estes, procariotos, leveduras, protozoários, plantas, invertebrados e vertebrados, incluindo o próprio Homo sapiens. Atualmente, mais de 2.000 outros projetos genoma estão em andamento, representando interesses médicos, comerciais, ambientais e industriais, ou contemplando organismos-modelos importantes para o desenvolvimento de pesquisas científicas. Aliada ao vertiginoso avanço da computação nas últimas décadas, a obtenção de seqüências genômicas completas de inúmeros organismos têm permitido o uso de abordagens holísticas e ao mesmo tempo inovadoras no estudo da estrutura, organização e evolução dos genomas e na predição e classificação funcional de genes, entre outros. Inúmeros bancos de dados e ferramentas computacionais de acesso público ou privado têm sido criados na tentativa de organizar e permitir acesso eficiente e rápido a estas informações através da internet. Nesta revisão apresentamos os principais recursos disponíveis publicamente na internet para a análise comparativa de genomas procarióticos, especialmente de genomas micobacterianos, grupo que contém importantes patógenos humanos e de animais. A Bioinformática e a Biologia Computacional, áreas do conhecimento responsáveis pelo desenvolvimento e aplicação de tais instrumentos computacionais, são também abordadas, enfatizando-se suas origens e contribuições para o desenvolvimento da ciência.