RESUMO

The Red Queen Hypothesis (RQH), derived from Lewis Carroll's "Through the Looking-Glass", postulates that organisms must continually adapt in response to each other to maintain relative fitness. Within the context of host-pathogen interactions, the RQH implies an evolutionary arms race, wherein viruses evolve to exploit hosts and hosts evolve to resist viral invasion. This study delves into the dynamics of the RQH in the context of virus-cell interactions, specifically focusing on virus receptors and cell receptors. We observed multiple virus-host systems and noted patterns of co-evolution. As viruses evolved receptor-binding proteins to effectively engage with cell receptors, cells countered by altering their receptor genes. This ongoing mutual adaptation cycle has influenced the molecular intricacies of receptor-ligand interactions. Our data supports the RQH as a driving force behind the diversification and specialization of both viral and host cell receptors. Understanding this co-evolutionary dance offers insights into the unpredictability of emerging viral diseases and potential therapeutic interventions. Future research is crucial to dissect the nuanced molecular changes and the broader ecological consequences of this ever-evolving battle. Here, we combine phylogenetic inferences, structural modeling, and molecular dynamics analyses to describe the epidemiological characteristics of major Brazilian DENV strains that circulated from 1990 to 2022 from a combined perspective, thus providing us with a more detailed picture on the dynamics of such interactions over time.

Assuntos

Moléculas de Adesão Celular , Vírus da Dengue , Evolução Molecular , Interações Hospedeiro-Patógeno , Receptores de Superfície Celular , Proteínas do Envelope Viral , Envelope Viral , Humanos , Brasil , Moléculas de Adesão Celular/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/química , Dengue/virologia , Vírus da Dengue/genética , Vírus da Dengue/metabolismo , Interações Hospedeiro-Patógeno/genética , Lectinas Tipo C/metabolismo , Lectinas Tipo C/genética , Lectinas Tipo C/química , Simulação de Dinâmica Molecular , Filogenia , Ligação Proteica , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/química , Receptores Virais/metabolismo , Receptores Virais/química , Receptores Virais/genética , Envelope Viral/metabolismo , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo , Proteínas do Envelope Viral/química

RESUMO

Rotavirus A (RVA) is a major cause of acute gastroenteritis globally that is classically genotyped by its two immunodominant outer capsid proteins, VP7 (G-) and VP4 (P-). Recent evidence suggests that the reassortant equine-like G3P[8] strain played a substantial role in RVA transmission in Brazil since 2015. To understand its global emergence and dissemination in Brazilian territory, stool samples collected from 11 Brazilian states (n = 919) were genotyped by RT-qPCR and proceeded to sequence the VP7 gene (n = 102, 79 being newly generated) of the G3P[8] samples with pronounced viral loads. Our phylogenetic genotyping showed that G3P[8] became the dominant strain in Brazil between 2017 and 2020, with equine-like variants representing 75%-100% of VP7 samples in this period. A Bayesian discrete phylogeographic analysis strongly suggests that the equine-like G3P[8] strain originated in Asia during the early 2010s and subsequently spread to Europe, the Caribbean, and South America. Multiple introductions were detected in Brazil between 2014 and 2017, resulting in five national clusters. The reconstruction of the effective population size of the largest Brazilian cluster showed an expansion until 2017, followed by a plateau phase until 2019 and subsequent contraction. Our study also supports that most mutations fixed during equine-like G3P[8] evolution were synonymous, suggesting that adaptive evolution was not an important driving force during viral dissemination in humans, potentially increasing its susceptibility to acquired immunity. This research emphasizes the need for comprehensive rotavirus genomic surveillance that allows close monitoring of its ever-shifting composition and informs more effective public health policies.IMPORTANCEOur original article demonstrated the origin and spread in a short time of equine-like G3P[8] in Brazil and the world. Due to its segmented genome, it allows numerous mechanisms including genetic drift and reassortment contribute substantially to the genetic diversity of rotavirus. Although the effectiveness and increasing implementation of vaccination have not been questioned, a matter of concern is its impact on the emergence of escape mutants or even the spread of unusual strains of zoonotic transmission that could drive epidemic patterns worldwide. This research emphasizes the need for comprehensive rotavirus genomic surveillance, which could facilitate the formulation of public policies aimed at preventing and mitigating its transmission.

Assuntos

Infecções por Rotavirus , Rotavirus , Animais , Cavalos/genética , Humanos , Rotavirus/genética , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/veterinária , Infecções por Rotavirus/genética , Brasil/epidemiologia , Filogenia , Teorema de Bayes , Genoma Viral , Genótipo

RESUMO

Zika virus (ZIKV) and dengue virus (DENV) share a lot of similarities being both phylogenetically closely related, share the same insect vector passage for reaching the host, affinity for the same carbohydrate receptor domains (CRDs), indicating feasible competition between them on the natural field. Here, we prospected interactions of both envelope proteins with a DC-SIGN, a transmembrane c-type lectine receptor with the most implicated CRD with the Flavivirus infection presents on dendritic cells involved in viruses replication processes into the host, and among rares CRD receptors susceptible to interacting with a broad of subtypes of DENV. Protein-protein docking procedures produced structures for molecular dynamics experiments, suggesting the most energetically favorable complex. The difference found in the deltaG results prompted the experimentation with molecular dynamics. To investigate further specific residues involved with such interactions we produced a decomposition analysis using molecular dynamics of the docked proteins evaluated afterward with the Generalized Born Surface Area method. Solvent-accessible surface area (SASA) analysis for both showed very similar but with a slight reduction for ZIKV_E, which agreed with residues SASA analysis highlighting regions more exposed in the ZIVK protein than in DENV. Despite residues PHE313 is reponsible for most of the interactions with the envelope of these arboviruses, ZIKV interacted with this residue in DC-SIGN with lower energies and using more interactions with not expexted residues GLU241 and ARG386. Taken together these results suggest better competitive interaction of ZIKV with the DC-SIGN receptor, particularly in the CRD portion.

Assuntos

Vírus da Dengue , Dengue , Infecção por Zika virus , Zika virus , Humanos , Simulação de Dinâmica Molecular

RESUMO

Studies of fungal communities through amplicon metagenomics in aquatic environments, particularly in freshwater ecosystems, are still relatively recent. Unfortunately, many of these water bodies are facing growing threats from human expansion, such as effluent discharge from various human activities. As a result, these effluents have the potential to significantly alter the characteristics of water bodies and, subsequently, impact the diversity of their resident microorganisms. In this context, our objective was to investigate whether the fungal community structure varies according to the presence of different anthropic disturbances. We expect (i) the diversity of fungi will be greater and (ii) more specific unique operational taxonomic units (OTUs) related to each ecotonal system will be found compared to other sites of a lagoon. The study was conducted in the Tramandaí Lagoon (subtropical southern Brazil) at four distinct sampling points (estuary, middle of the lagoon, crop field area, and near a residential area where the Tramandaí River flows into the lagoon). As expected, the estuary and residential zones, which are ecotones, exhibited greater fungal diversity and more specific OTUs compared to the middle of the lagoon and crop field area. Moreover, a substantial proportion of fungal taxa could not be identified at the genus level, with many only classified at the phylum level, indicating potential new lineages. These findings underscore our limited understanding of the subtropical freshwater mycobiota.

RESUMO

Ophiocordyceps australis (Ascomycota, Hypocreales, Ophiocordycipitaceae) is a classic entomopathogenic fungus that parasitizes ants (Hymenoptera, Ponerinae, Ponerini). Nonetheless, according to our results, this fungal species also exhibits a complete set of genes coding for plant cell wall degrading Carbohydrate-Active enZymes (CAZymes), enabling a full endophytic stage and, consequently, its dual ability to both parasitize insects and live inside plant tissue. The main objective of our study was the sequencing and full characterization of the genome of the fungal strain of O. australis (CCMB661) and its predicted secretome. The assembled genome had a total length of 30.31 Mb, N50 of 92.624 bp, GC content of 46.36%, and 8,043 protein-coding genes, 175 of which encoded CAZymes. In addition, the primary genes encoding proteins and critical enzymes during the infection process and those responsible for the host-pathogen interaction have been identified, including proteases (Pr1, Pr4), aminopeptidases, chitinases (Cht2), adhesins, lectins, lipases, and behavioral manipulators, such as enterotoxins, Protein Tyrosine Phosphatases (PTPs), and Glycoside Hydrolases (GHs). Our findings indicate that the presence of genes coding for Mad2 and GHs in O. australis may facilitate the infection process in plants, suggesting interkingdom colonization. Furthermore, our study elucidated the pathogenicity mechanisms for this Ophiocordyceps species, which still is scarcely studied.

RESUMO

Staphylococcus aureus is the main etiological agent of mastitis in small ruminants worldwide. This disease has a difficult cure and possible relapse, leading to significant economic losses in production, milk quality and livestock. This study performed comparative genomic analyses between 73 S. aureus genomes from different hosts (human, bovine, pig and others). This work isolated and sequenced 12 of these genomes from ovine. This study contributes to the knowledge of genomic specialization and the role of specific genes in establishing infection in ovine mastitis-associated S. aureus. The genomes of S. aureus isolated from sheep maintained a higher representation when grouped with clonal complexes 130 and 133. The genomes showed high genetic similarity, the species pan-genome consisting of 4200 genes (central = 2008, accessory = 1559 and unique = 634). Among these, 277 unique genes were related to the genomes isolated from sheep, with 39.6 % as hypothetical proteins, 6.4 % as phages, 6.4 % as toxins, 2.9 % as transporters, and 44.7 % as related to other proteins. Furthermore, at the pathogen level, they showed 80 genes associated with virulence factors and 19 with antibiotic resistance shared in almost all isolates. Although S. aureus isolated from ovine showed susceptibility to antimicrobials in vitro, ten genes were predicted to be associated with antibiotic inactivation and efflux pump, suggesting resistance to gentamicin and penicillin. This work may contribute to identifying genes acquired by horizontal transfer and their role in host adaptation, virulence, bacterial resistance, and characterization of strains affecting ovine.

Assuntos

Mastite Bovina , Infecções Estafilocócicas , Feminino , Animais , Bovinos , Ovinos/genética , Humanos , Suínos , Fatores de Virulência/genética , Staphylococcus aureus/genética , Adaptação ao Hospedeiro , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/veterinária , Infecções Estafilocócicas/microbiologia , Ruminantes/genética , Genômica , Sequências Repetitivas Dispersas , Mastite Bovina/genética , Mastite Bovina/microbiologia

RESUMO

The Spike protein's structure of the SARS-CoV-2 provides a unique opportunity to consider perturbations at the atomic level. We used the cryo-electron microscopy structure of the open conformation of the Spike protein to assess the impact of the mutations observed in the variants of concern at the molecular level. Molecular dynamics were subsequently performed with both the wt and the mutated forms to compare the flexibility and variation data for each residue of the three-dimensional fluctuations in the region associated with each alpha carbon. Additionally, protein-protein docking was used to investigate the interaction of each mutated profile with the ACE-2 receptor. After the molecular dynamics, the results show that the mutations increased the stability of the trimeric protein, with greater stability observed in the Gamma variant harboring the 10 characteristic mutations. The results of molecular dynamics, as shown by RMSF demonstrated for the residues that comprise the binding domain receptor (RBD), exhibited a reduction in flexibility, which was more pronounced in the Gamma variant. Finally, protein-protein docking experiments revealed an increase in the number of hydrophobic interactions and hydrogen bonds in the Gamma variant against the ACE-2 receptor, as opposed to the other variants. Taken together, these in silico experiments suggest that the evolution of the mutations favored the increased stability of Spike protein while potentially improving its interaction with the ACE-2 receptor, which in turn may indicate putative structural outcomes of the selection of these mutations in the convergent adaptive evolution as it has been observed for SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Assuntos

COVID-19 , Glicoproteína da Espícula de Coronavírus , Humanos , Glicoproteína da Espícula de Coronavírus/genética , Simulação de Dinâmica Molecular , COVID-19/genética , Microscopia Crioeletrônica , SARS-CoV-2/genética , Mutação , Ligação Proteica

RESUMO

Colorectal cancer (CRC) commonly arises in individuals with premalignant colon lesions known as polyps, with both conditions being influenced by gut microbiota. Host-related factors and inherent characteristics of polyps and tumors may contribute to microbiome variability, potentially acting as confounding factors in the discovery of taxonomic biomarkers for both conditions. In this study we employed shotgun metagenomics to analyze the taxonomic diversity of bacteria present in fecal samples of 90 clinical subjects (comprising 30 CRC patients, 30 with polyps and 30 controls). Our findings revealed a decrease in taxonomic richness among individuals with polyps and CRC, with significant dissimilarities observed among the study groups. We identified significant alterations in the abundance of specific taxa associated with polyps (Streptococcaceae, Lachnoclostridium, and Ralstonia) and CRC (Lactobacillales, Clostridiaceae, Desulfovibrio, SFB, Ruminococcus, and Faecalibacterium). Clostridiaceae exhibited significantly lower abundance in the early stages of CRC. Additionally, our study revealed a positive co-occurrence among underrepresented genera in CRC, while demonstrating a negative co-occurrence between Faecalibacterium and Desulfovibrio, suggesting potential antagonistic relationships. Moreover, we observed variations in taxonomic richness and/or abundance within the polyp and CRC bacteriome linked to polyp size, tumor stage, dyslipidemia, diabetes with metformin use, sex, age, and family history of CRC. These findings provide potential new biomarkers to enhance early CRC diagnosis while also demonstrating how intrinsic host factors contribute to establishing a heterogeneous microbiome in patients with CRC and polyps.

RESUMO

Aspergillus welwitschiae causes bole rot disease in sisal (Agave sisalana and related species) which affects the production of natural fibers in Brazil, the main worldwide producer of sisal fibers. This fungus is a saprotroph with a broad host range. Previous research established A. welwitschiae as the only causative agent of bole rot in the field, but little is known about the evolution of this species and its strains. In this work, we performed a comparative genomics analysis of 40 Aspergillus strains. We show the conflicting molecular identity of this species, with one sisal-infecting strain sharing its last common ancestor with Aspergillus niger, having diverged only 833 thousand years ago. Furthermore, our analysis of positive selection reveals sites under selection in genes coding for siderophore transporters, Sodium­calcium exchangers, and Phosphatidylethanolamine-binding proteins (PEBPs). Herein, we discuss the possible impacts of these gene functions on the pathogenicity in sisal.

Assuntos

Agave , Agave/genética , Brasil , Aspergillus/genética

RESUMO

Syphilis, a sexually transmitted infection caused by the spirochete Treponema pallidum, has seen a resurgence over the past years. T. pallidum is capable of early dissemination and immune evasion, and the disease continues to be a global healthcare burden. The purpose of this study was to design a multi-epitope immunogen through an immunoinformatics-based approach. Multi-epitope immunogens constitute carefully selected epitopes belonging to conserved and essential bacterial proteins. Several physico-chemical characteristics, such as antigenicity, allergenicity, and stability, were determined. Further, molecular docking and dynamics simulations were performed, ensuring binding affinity and stability between the immunogen and TLR-2. An in silico cloning was performed using the pET-28a(+) vector and codon adaptation for E. coli. Finally, an in silico immune simulation was performed. The in silico predictions obtained in this work indicate that this construct would be capable of inducing the requisite immune response to elicit protection against T. pallidum. Through this methodology we have designed a promising potential vaccine candidate for syphilis, namely Tpme-VAC/LGCM-2022. However, it is necessary to validate these findings in in vitro and in vivo assays.