RESUMO
Vector-borne diseases are globally prevalent and represent a major socioeconomic problem worldwide. Blood-sucking arthropods transmit most pathogenic agents that cause these human infections. The pathogens transmission to their vertebrate hosts depends on how efficiently they infect their vector, which is particularly impacted by the microbiota residing in the intestinal lumen, as well as its cells or internal organs such as ovaries. The balance between costs and benefits provided by these interactions ultimately determines the outcome of the relationship. Here, we will explore aspects concerning the nature of microbe-vector interactions, including the adaptive traits required for their establishment, the varied outcomes of symbiotic interactions, as well as the factors influencing the transition of these relationships across a continuum from parasitism to mutualism.
Assuntos
Vetores Artrópodes , Simbiose , Animais , Vetores Artrópodes/microbiologia , Vetores Artrópodes/parasitologia , Insetos Vetores/microbiologia , Insetos Vetores/fisiologia , Doenças Transmitidas por Vetores/transmissãoRESUMO
Blood-feeding arthropods are considered an enormous public health threat. They are vectors of a plethora of infectious agents that cause potentially fatal diseases like Malaria, Dengue fever, Leishmaniasis, and Lyme disease. These vectors shine due to their own physiological idiosyncrasies, but one biological aspect brings them all together: the requirement of blood intake for development and reproduction. It is through blood-feeding that they acquire pathogens and during blood digestion that they summon a collection of multisystemic events critical for vector competence. The literature is focused on how classical immune pathways (Toll, IMD, and JAK/Stat) are elicited throughout the course of vector infection. Still, they are not the sole determinants of host permissiveness. The dramatic changes that are the hallmark of the insect physiology after a blood meal intake are the landscape where a successful infection takes place. Dominant processes that occur in response to a blood meal are not canonical immunological traits yet are critical in establishing vector competence. These include hormonal circuitries and reproductive physiology, midgut permeability barriers, midgut homeostasis, energy metabolism, and proteolytic activity. On the other hand, the parasites themselves have a role in the outcome of these blood triggered physiological events, consistently using them in their favor. Here, to enlighten the knowledge on vector-pathogen interaction beyond the immune pathways, we will explore different aspects of the vector physiology, discussing how they give support to these long-dated host-parasite relationships.
RESUMO
Brain Expressed X-linked (BEX) protein family consists of five members in humans and is highly expressed during neuronal development. They are known to participate in cell cycle and in signaling pathways involved in neurodegeneration and cancer. BEX3 possess a conserved leucine-rich nuclear export signal and experimental data confirmed BEX3 nucleocytoplasmic shuttling. Previous data revealed that mouse BEX3 auto-associates in an oligomer rich in intrinsic disorder. In this work, we show that human BEX3 (hBEX3) has well-defined three-dimensional structure in the presence of small fragments of tRNA (tRFs). Conversely, the nucleic acids-free purified hBEX3 presented disordered structure. Small-angle X-ray scattering data revealed that in the presence of tRFs, hBEX3 adopts compact globular fold, which is very distinct from the elongated high-order oligomer formed by the pure protein. Furthermore, microscopy showed that hBEX3 undergoes condensation in micron-sized protein-rich droplets in vitro. In the presence of tRFs, biomolecular condensates were smaller and in higher number, showing acridine orange green fluorescence emission, which corroborated with the presence of base-paired nucleic acids. Additionally, we found that over time hBEX3 transits from liquid condensates to aggregates that are reversible upon temperature increment and dissolved by 1,6-hexanediol. hBEX3 assemblies display different morphology in the presence of the tRFs that seems to protect from amyloid formation. Collectively, our findings support a role for tRFs in hBEX3 disorder-to-order transition and modulation of phase transitions. Moreover, hBEX3 aggregation-prone features and the specificity in interaction with tRNA fragments advocate paramount importance toward understanding BEX family involvement in neurodevelopment and cell death.
Assuntos
Proteínas Reguladoras de Apoptose/química , Regulação da Expressão Gênica , RNA Bacteriano/genética , RNA de Transferência/genética , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Escherichia coli/genética , Humanos , Transição de Fase , Conformação Proteica , RNA Bacteriano/química , RNA de Transferência/químicaRESUMO
The selenium-dependent glutathione peroxidase (SeGPx) is a well-studied enzyme that detoxifies organic and hydrogen peroxides and provides cells or extracellular fluids with a key antioxidant function. The presence of a SeGPx has not been unequivocally demonstrated in insects. In the present work, we identified the gene and studied the function of a Rhodnius prolixus SeGPx (RpSeGPx). The RpSeGPx mRNA presents the UGA codon that encodes the active site selenocysteine (Sec) and a corresponding Sec insertion sequence (SECIS) in the 3' UTR region. The encoded protein includes a signal peptide, which is consistent with the high levels of GPx enzymatic activity in the insect's hemolymph, and clusters phylogenetically with the extracellular mammalian GPx03. This result contrasts with all other known insect GPxs, which use a cysteine residue instead of Sec and cluster with the mammalian phospholipid hydroperoxide GPx04. RpSeGPx is widely expressed in insect organs, with higher expression levels in the fat body. RNA interference (RNAi) was used to reduce RpSeGPx gene expression and GPx activity in the hemolymph. Adult females were apparently unaffected by RpSeGPx RNAi, whereas first instar nymphs showed a three-day delay in ecdysis. Silencing of RpSeGPx did not alter the gene expression of the antioxidant enzymes catalase, xanthine dehydrogenase and a cysteine-GPx, but it reduced the levels of the dual oxidase and NADPH oxidase 5 transcripts that encode for enzymes releasing extracellular hydrogen peroxide/superoxide. Collectively, our data suggest that RpSeGPx functions in the regulation of extracellular (hemolymph) redox homeostasis of R. prolixus.
Assuntos
Glutationa Peroxidase/química , Glutationa Peroxidase/genética , Rhodnius/enzimologia , Rhodnius/genética , Selênio/química , Animais , Feminino , Inativação Metabólica/genética , Muda , Filogenia , Interferência de RNA , Coelhos , Rhodnius/crescimento & desenvolvimento , Selenocisteína/químicaRESUMO
Trypanosoma cruzi is a hemoflagellate protozoan that causes Chagas' disease. The life cycle of T. cruzi is complex and involves different evolutive forms that have to encounter different environmental conditions provided by the host. Herein, we performed a functional assessment of mitochondrial metabolism in the following two distinct evolutive forms of T. cruzi: the insect stage epimastigote and the freshly isolated bloodstream trypomastigote. We observed that in comparison to epimastigotes, bloodstream trypomastigotes facilitate the entry of electrons into the electron transport chain by increasing complex II-III activity. Interestingly, cytochrome c oxidase (CCO) activity and the expression of CCO subunit IV were reduced in bloodstream forms, creating an "electron bottleneck" that favored an increase in electron leakage and H(2)O(2) formation. We propose that the oxidative preconditioning provided by this mechanism confers protection to bloodstream trypomastigotes against the host immune system. In this scenario, mitochondrial remodeling during the T. cruzi life cycle may represent a key metabolic adaptation for parasite survival in different hosts.
Assuntos
Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/metabolismo , Estágios do Ciclo de Vida/fisiologia , Mitocôndrias/metabolismo , Proteínas de Protozoários/metabolismo , Trypanosoma cruzi/metabolismo , Adaptação Fisiológica/fisiologia , Animais , Doença de Chagas/imunologia , Doença de Chagas/metabolismo , Doença de Chagas/parasitologia , Complexo II de Transporte de Elétrons/imunologia , Complexo III da Cadeia de Transporte de Elétrons/imunologia , Humanos , Peróxido de Hidrogênio/imunologia , Peróxido de Hidrogênio/metabolismo , Mitocôndrias/imunologia , Proteínas de Protozoários/imunologia , Trypanosoma cruzi/crescimento & desenvolvimento , Trypanosoma cruzi/imunologiaRESUMO
A crude polysaccharide obtained from mycelium of Fusarium solani by treatment with 2 per center KOH/2h/100§C and fractionated by gel filtration chromatography yielded three fractions denoted L1,L2 and L3. Chemical analysis of the crude polysaccharide showed the presence od 89,5 per center total carbohydrate, 4 per center protin 14 per center uronic acid, traces of phosphate and hexosamine. Mannose, galactose, glucose and unidentifid pentose, were present in a 27.5:34:34.5:4 molar ratio.