RESUMO
The recent global outbreak of mpox, caused by monkeypox virus (MPV) emerged in Europe in 2022 and rapidly spread to over 40 countries. The Americas are currently facing the highest impact, reporting over 50,000 cases by early 2023. In this study, we analyzed 880 MPV isolates worldwide to gain insights into the evolutionary patterns and initial introduction events of the virus in Mexico. We found that MPV entered Mexico on multiple occasions, from the United Kingdom, Portugal, and Canada, and subsequently spread locally in different regions of Mexico. Additionally, we show that MPV has an open pangenome, highlighting the role of gene turnover in shaping its genomic diversity, rather than single-nucleotide polymorphisms (SNPs), which do not contribute significantly to genome diversity. Although the genome contains multiple SNPs in coding regions, these remain under purifying selection, suggesting their evolutionary conservation. One notable exception is amino acid position 63 of the protein encoded by the Cop-A4L gene, which is intricately related to viral maturity, which we found to be under strong positive selection. Ancestral state reconstruction indicated that the ancestral state at position 63 corresponds to the amino acid valine, which is present only in isolates of clade I. However, the isolates from the current outbreak contained threonine at position 63. Our findings contribute new information about the evolution of monkeypox virus.
Assuntos
Mpox , Humanos , Monkeypox virus/genética , México/epidemiologia , Filogenia , Aminoácidos/genética , Surtos de DoençasRESUMO
BACKGROUND: Mycobacterium abscessus (MAB) is a widely disseminated pathogenic non-tuberculous mycobacterium (NTM). Like with the M. tuberculosis complex (MTBC), excreted / secreted (ES) proteins play an essential role for its virulence and survival inside the host. Here, we used a robust bioinformatics pipeline to predict the secretome of the M. abscessus ATCC 19977 reference strain and 15 clinical isolates belonging to all three MAB subspecies, M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp. massiliense. RESULTS: We found that ~ 18% of the proteins encoded in the MAB genomes were predicted as secreted and that the three MAB subspecies shared > 85% of the predicted secretomes. MAB isolates with a rough (R) colony morphotype showed larger predicted secretomes than isolates with a smooth (S) morphotype. Additionally, proteins exclusive to the secretomes of MAB R variants had higher antigenic densities than those exclusive to S variants, independent of the subspecies. For all investigated isolates, ES proteins had a significantly higher antigenic density than non-ES proteins. We identified 337 MAB ES proteins with homologues in previously investigated M. tuberculosis secretomes. Among these, 222 have previous experimental support of secretion, and some proteins showed homology with protein drug targets reported in the DrugBank database. The predicted MAB secretomes showed a higher abundance of proteins related to quorum-sensing and Mce domains as compared to MTBC indicating the importance of these pathways for MAB pathogenicity and virulence. Comparison of the predicted secretome of M. abscessus ATCC 19977 with the list of essential genes revealed that 99 secreted proteins corresponded to essential proteins required for in vitro growth. CONCLUSIONS: This study represents the first systematic prediction and in silico characterization of the MAB secretome. Our study demonstrates that bioinformatics strategies can help to broadly explore mycobacterial secretomes including those of clinical isolates and to tailor subsequent, complex and time-consuming experimental approaches accordingly. This approach can support systematic investigation exploring candidate proteins for new vaccines and diagnostic markers to distinguish between colonization and infection. All predicted secretomes were deposited in the Secret-AAR web-server ( http://microbiomics.ibt.unam.mx/tools/aar/index.php ).
Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Mycobacterium tuberculosis , Humanos , Mycobacterium abscessus/genéticaRESUMO
The secretome refers to all the Excreted/Secreted (ES) proteins of a cell, and these are involved in critical biological processes, such as cell-cell communication, and host immune responses. Recently, we introduced the Abundance of Antigenic Aegions (AAR) value to assess the protein antigenic density and to evaluate the antigenic potential of secretomes. Here, to facilitate the AAR calculation, we implemented it as a user-friendly webserver. We extended the webserver capabilities implementing a sequence-based tool for searching homologous proteins across secretomes, including experimental and predicted secretomes of Mycobacterium tuberculosis and Taenia solium. Additionally, twelve secretomes of helminths, five of Mycobacterium and two of Gram-negative bacteria are also available. Our webserver is a useful tool for researchers working on immunoinformatics and reverse vaccinology, aiming at discovering candidate proteins for new vaccines or diagnostic tests, and it can be used to prioritize the experimental analysis of proteins for druggability assays. The Secret-AAR web server is available at http://microbiomics.ibt.unam.mx/tools/aar/.
Assuntos
Antígenos de Bactérias/imunologia , Antígenos de Helmintos/imunologia , Proteínas de Bactérias/imunologia , Proteínas de Helminto/imunologia , Mycobacterium tuberculosis/imunologia , Software , Taenia solium/imunologia , Animais , Internet , Mycobacterium tuberculosis/metabolismo , Proteoma/análise , Proteoma/imunologia , Taenia solium/metabolismoRESUMO
IMPORTANCE: Prophages play an important role in shaping the genetic diversity and evolution of their hosts. Acquisition or loss of prophages can lead to genomic variations, including changes in the bacterial phenotype promoted by recombination events, genetic repertoire exchanges and dissemination of virulence factors, and antibiotic resistance. By studying prophages in Campylobacter species, scientists can gain insights into the evolutionary patterns, pathogenicity mechanisms, epidemiology, and population dynamics of these species. This has implications for public health, antibiotic resistance surveillance, and the development of targeted therapeutic approaches.
Assuntos
Bacteriófagos , Campylobacter , Prófagos/genética , Campylobacter/genética , Virulência , Fatores de Virulência , Recombinação Genética , Bacteriófagos/genéticaRESUMO
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
Microbiome sequencing has become the standard procedure in the study of new ecological and human-constructed niches. To our knowledge, this is the first report of a metagenome from the water of a greenhouse drain. We found that the greenhouse is not a diverse niche, mainly dominated by Rhizobiales and Rodobacterales. The analysis of the functions encoded in the metagenome showed enrichment of characteristic features of soil and root-associated bacteria such as ABC-transporters and hydrolase enzymes. Additionally, we found antibiotic resistances genes principally for spectinomycin, tetracycline, and aminoglycosides. This study aimed to identify the bacteria and functional gene composition of a greenhouse water drain sample and also provide a genomic resource to search novel proteins from a previously unexplored niche. All the metagenome proteins and their annotations are available to the scientific community via http://microbiomics.ibt.unam.mx/tools/metagreenhouse/.