RESUMO
Phages and prophages are one of the principal modulators of microbial populations. However, much of their diversity is still poorly understood. Here, we extracted 33,624 prophages from 13,713 complete prokaryotic genomes to explore the prophage diversity and their relationships with their host. Our results reveal that prophages were present in 75% of the genomes studied. In addition, Enterobacterales were significantly enriched in prophages. We also found that pathogens are a significant reservoir of prophages. Finally, we determined that the prophage relatedness and the range of genomic hosts were delimited by the evolutionary relationships of their hosts. On a broader level, we got insights into the prophage population, identified in thousands of publicly available prokaryotic genomes, by comparing the prophage distribution and relatedness between them and their hosts. IMPORTANCE Phages and prophages play an essential role in controlling their host populations either by modulating the host abundance or providing them with genes that benefit the host. The constant growth in next-generation sequencing technology has caused the development of powerful computational tools to identify phages and prophages with high precision. Making it possible to explore the prophage populations integrated into host genomes on a large scale. However, it is still a new and under-explored area, and efforts are still required to identify prophage populations to understand their dynamics with their hosts.
Assuntos
Bacteriófagos , Prófagos , Prófagos/genética , Especificidade de Hospedeiro , Bacteriófagos/genética , Genômica , Genoma Viral/genéticaRESUMO
The microbiota in broiler chicken intestines affects the animals' health, metabolism, and immunity both positively and negatively. Accordingly, it has a significant impact on animal productivity. Phages, host-specific parasites of bacterial cells, are a promising antimicrobial alternative that selectively target pathogens without disturbing the microbiota. The purpose of this study is to further characterize the commensal microbial community at production scale in broiler chickens treated with a Salmonella phage treatment. We evaluated the cecal microbiota of broilers reared in a commercial farming system where a phage cocktail against Salmonella, SalmoFree was supplied to animals. To do so, two field trials were conducted, incorporating three doses of phages in the broilers' drinking water. Our results showed that the core microbiome (taxa that were present in more than 50% of samples) contained species that are key to microbiota adaptation in the last stage of the production cycle. Among these, there are some important degraders of complex polysaccharides and producers of short chain fatty acids (SCFA) such as Eisenbergiella and Lachnoclostridium. The phage cocktail did not affect the normal development of the microbiota's structure. The addition of the phage cocktail resulted in a significant reduction in Campylobacter and an increase in Butyricimonas, Helicobacter and Rikenellaceae, which are common inhabitants in chicken gut with known negative and positive effects on their health and metabolism. Altogether, we consider that these results contribute valuable information to the implementation of large-scale phage therapy technologies.
Assuntos
Galinhas/microbiologia , Microbioma Gastrointestinal , Terapia por Fagos/veterinária , Fagos de Salmonella , Administração Oral , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Ceco/microbiologia , Doenças das Aves Domésticas/prevenção & controle , RNA Ribossômico 16SRESUMO
Bacteriophages are considered the most abundant biological entities on earth, and they are able to modulate the populations of their bacterial hosts. Although the potential of bacteriophages has been accepted as an alternative strategy to combat multidrug-resistant pathogenic bacteria, there still exists a considerable knowledge gap regarding their genetic diversity, which hinders their use as antimicrobial agents. In this study, we undertook a genomic and phylogenetic characterization of the phage Ab11510-phi, which was isolated from a multidrug-resistant Acinetobacter baumannii strain (Ab11510). We found that Ab11510-phi has a narrow host range and belongs to a small group of transposable phages of the genus Vieuvirus that have only been reported to infect Acinetobacter bacteria. Finally, we showed that Ab11510-phi (as well as other vieuvirus phages) has a high level of mosaicism. On a broader level, we demonstrate that comparative genomics and phylogenetic analysis are necessary tools for the proper characterization of phage diversity.
Assuntos
Acinetobacter baumannii/virologia , Farmacorresistência Bacteriana Múltipla , Siphoviridae/classificação , Siphoviridae/genética , Acinetobacter baumannii/fisiologia , Bacteriófagos/classificação , Bacteriófagos/genética , Bacteriófagos/fisiologia , DNA Viral/genética , Genoma Viral/genética , Genômica , Especificidade de Hospedeiro , Filogenia , Siphoviridae/fisiologia , Proteínas Virais/genéticaRESUMO
Cyclin-Dependent Kinase 2 (CDK2) and Vascular Endothelial Growth Factor Receptor (VEGFR2) have largely been considered as attractive targets for developing anticancer agents. However, there is no dual inhibitor commercially available in the market that interacts simultaneously with the allosteric back pocket of these enzymes. We applied a combined computational strategy that started with the generation of two overlapping pharmacophore models of both kinases at 'inactive' conformation. Next, several virtual libraries of natural products, including the databases TCM (Traditional Chinese Medicine), UEFS (Universidade Estadual de Feira de Santana), NuBBE (Nuclei of Bioassays, Biosynthesis, and Ecophysiology of Natural Products) and AfroDb (African Medicinal Plants Database) were deconstructed using a non-extensive version of the approach RECAP (retrosynthetic combinatorial analysis procedure). These natural-product-derived fragments (NPDFs) were screened and merged into drug-sized compounds, which were filtered by Lipinski's Rule-of-five (Ro5) and docking. As a result, two pharmacophore models, namely Hypo1 and Hypo2, were developed with an accuracy of 0.94 and 0.84, respectively. Deconstruction of natural products produced a set of 16655 unique non-extensive NPDFs that were screened against both pharmacophore models. Finally, after merging, Ro5-filtering and docking, we obtained a set of 20 hit compounds predicted to be diverse, developable, synthesizable and potent. The computational strategy proved successful to find virtual candidates of kinase inhibitors and therefore contributes to the identification of innovative multi-target compounds with potential anticancer activity. Communicated by Ramaswamy H. Sarma.
Assuntos
Antineoplásicos , Produtos Biológicos , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Simulação de Acoplamento MolecularRESUMO
Acute hepatopancreatic necrosis disease (AHPND) has extended rapidly, causing alarming shrimp mortalities. Initially, the only known causative agent was Vibrio parahaemolyticus carrying a plasmid coding for the mortal toxins PirVP. Recently, it has been found that the plasmid and hence the disease, could be transferred among members of the Harveyi clade. The current study performs a genomic characterization of an isolate capable of developing AHPND in shrimp. Mortality studies and molecular and histopathological analyses showed the infection capacity of the strain. Multilocus sequence analysis placed the bacteria as a member of the Orientalis clade, well known for containing commensal and even probiotic bacteria used in the shrimp industry. Further whole genome comparative analyses, including Vibrio species from the Orientalis clade, and phylogenomic metrics (TETRA, ANI and DDH) showed that the isolate belongs to a previously unidentified species, now named Vibrio punensis sp. nov. strain BA55. Our findings show that the gene transfer capacity of Vibrio species goes beyond the clade classification, demonstrating a new pathogenic capacity to a previously known commensal clade. The presence of these genes in a different Vibrio clade may contribute to the knowledge of the Vibrio pathogenesis and has major implications for the spread of emerging diseases.