The largest monkeypox virus (MPXV) outbreak described so far in non-endemic countries was identified in May 2022 (refs. 1–6). In this study, shotgun metagenomics allowed the rapid reconstruction and phylogenomic characterization of the first MPXV outbreak genome sequences, showing that this MPXV belongs to clade 3 and that the outbreak most likely has a single origin. Although 2022 MPXV (lineage B.1) clustered with 2018–2019 cases linked to an endemic country, it segregates in a divergent phylogenetic branch, likely reflecting continuous accelerated evolution. An in-depth mutational analysis suggests the action of host APOBEC3 in viral evolution as well as signs of potential MPXV human adaptation in ongoing microevolution. Our findings also indicate that genome sequencing may provide resolution to track the spread and transmission of this presumably slow-evolving double-stranded DNA virus.

We compared 19,207 cases of SARS-CoV-2 variant B.1.1.7/S gene target failure (SGTF), 436 B.1.351 and 352 P.1 to non-variant cases reported by seven European countries. COVID-19 cases with these variants had significantly higher adjusted odds ratios for hospitalisation (B.1.1.7/SGTF: 1.7, 95% confidence interval (CI): 1.0–2.9; B.1.351: 3.6, 95% CI: 2.1–6.2; P.1: 2.6, 95% CI: 1.4–4.8) and B.1.1.7/SGTF and P.1 cases also for intensive care admission (B.1.1.7/SGTF: 2.3, 95% CI: 1.4–3.5; P.1: 2.2, 95% CI: 1.7–2.8).

RESUMO A designação "espécies reactivas" (ER) é utilizada para englobar os radicais livres e outras moléculas, as quais, apesar de não possuírem átomos com electrões desemparelhados, são potencialmente geradoras desses radicais. Estas substâncias, naturalmente formadas em situações basais pelo metabolismo celular, são capazes, devido à sua elevada reactividade, de modificar a maioria das moléculas biológicas, colocando em risco a funcionalidade e a viabilidade celular. Particularmente a nível muscular esquelético, a mitocôndria parece constituir a principal fonte e, simultaneamente, o principal alvo das ER. No entanto, a Xantina Oxidase, a Fosfolipase A2, a desaminação das catecolaminas, assim como a infiltração tecidual pós-exercício de leucócitos, poderão contribuir também como fontes adicionais de ER nos músculos exercitados. A ocorrência e a intensidade do resultante dano oxidativo, tanto no músculo esquelético, como nos restantes órgãos e tecidos corporais, para além da taxa de síntese de ER, estão também dependente da capacidade antioxidante que o tecido expressa, quer à custa de antioxidantes endógenos, quer exógenos provenientes da dieta. Essa capacidade antioxidante depende não só do papel específico de cada um dos mecanismos antioxidantes, enzimáticos e não enzimáticos, como também da cooperação entre os mesmos. Como resultado do exercício físico agudo, as taxas de produção de ER de oxigénio aumentam, tal como o dano muscular causado por estes mesmos compostos. Contudo, com a repetição regular do exercício físico (treino), os resultados da literatura mostram que os músculos aumentam a sua capacidade antioxidante, tornando-os mais protegidos contra as ER formadas, não só em repouso, como também durante os exercícios agudos subsequentes.

Chlamydia trachomatis is a human bacterial pathogen that multiplies only within an intracellular membrane-bound vacuole, the inclusion. C. trachomatis includes ocular and urogenital strains, usually causing infections restricted to epithelial cells of the conjunctiva and genital mucosa, respectively, and lymphogranuloma venereum (LGV) strains, which can infect macrophages and spread into lymph nodes. However, C. trachomatis genomes display >98% identity at the DNA level. In this work, we studied whether C. trachomatis Inc proteins, which have a bilobed hydrophobic domain that may mediate their insertion in the inclusion membrane, could be a factor determining these different types of infection and tropisms. Analyses of polymorphisms and phylogeny of 48 Inc proteins from 51 strains encompassing the three disease groups showed significant amino acid differences that were mainly due to variations between Inc proteins from LGV and ocular or urogenital isolates. Studies of the evolutionary dynamics of inc genes suggested that 10 of them are likely under positive selection and indicated that most nonsilent mutations are LGV specific. Additionally, real-time quantitative PCR analyses in prototype and clinical strains covering the three disease groups identified three inc genes with LGV-specific expression. We determined the transcriptional start sites of these genes and found LGV-specific nucleotides within their promoters. Thus, subtle variations in the amino acids of a subset of Inc proteins and in the expression of inc genes may contribute to the unique tropism and invasiveness of C. trachomatis LGV strains.

Chlamydia trachomatis maintain a conserved plasmid, which is a primary regulator of chromosomal genes, but there is no experimental evidences associating it with the strains' differential tissue tropism (ocular and genital mucosae, and lymph nodes). We investigated if the number of plasmids per strain correlate with expression profiles of plasmid ORFs and small anti-sense RNAs (sRNAs), and also if these molecular features underlie tropism dissimilarities. We performed absolute and relative qPCR to determine both the plasmid load and expression throughout C. trachomatis development. Our findings suggest that plasmid load (never exceeding 8 copies) is not a function of expression needs and does not reflect tissue tropism. However, for most ORFs, ocular strains presented lower expression than genital or lymphogranuloma venereum (LGV) strains, and ORF6/pgp4 (transcriptional regulator of virulence associated genes) presented the highest mean expression among strains, followed by the virulence factor ORF5/pgp3 (also regulated by ORF6/pgp4). More, the mean expression levels of the sRNA-2 (anti-sense to ORF2/pgp8) were up to 100-fold higher than those of the ORFs, and up to 12-fold higher than that of sRNA-7 (anti-sense to ORF7/pgp5) for the LGV strains. Overall, besides the known regulatory role of C. trachomatis plasmid, its transcriptional dynamics sustains tropism differences.

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On behalf of the host-pathogen "arms race," a cutting-edge approach for elucidating genotype-phenotype relationships relies on the identification of positively selected loci involved in pathoadaptation. We studied the obligate intracellular bacterium Chlamydia trachomatis, for which same-species strains display a nearly identical core and pan genome, while presenting a wide range of tissue tropism and ecological success. We sought to evaluate the evolutionary patterns underlying species separation (divergence) and C. trachomatis serovar radiation (polymorphism) and to establish genotype-phenotype associations. By analyzing 60 Chlamydia strains, we detected traces of Muller's ratchet as a result of speciation and identified positively selected genes and codons hypothetically involved in the infection of different human cell types (e.g., columnar epithelial cells of ocular or genital mucosae and mononuclear phagocytes) and also events likely driving pathogenic and ecological success dissimilarities. In general, these genes code for proteins involved in immune response elicitation, proteolysis, and the subversion of host-cell functions, and also for proteins with unknown function(s). Several genes are potentially involved in more than one adaptive process, suggesting multiple functions or a distinct modus operandi for a specific function, and thus should be considered as crucial research targets. In addition, six of the nine genes encoding the putative antigen/adhesin polymorphic membrane proteins seem to be under positive selection along specific serovars, which sustains an essential biological role of this extra-large paralogue family in chlamydial pathobiology. This study provides insight into how evolutionary inferences illuminate ecological processes such as adaptation to different niches, pathogenicity, or ecological success driven by arms races. G enomic changes of microbial pathogens are directly linked to the evolutionary "arms race" that takes place between microbe and host during the infectious process, as a result of the antagonistic interaction, and they are a consequence of polymorphisms accumulated after selective pressure from the host's inflammatory or immune response (32). However, the majority of coding genes present a higher number of synonymous rather than nonsynonymous substitutions, which indicates that purifying selection is operating to preserve the current function and structure of the protein, and only a small fraction of the genes are expected to be positively selected where diversification is favored through increased fitness (11). In order to understand the evolutionary forces that act on gene variation, major challenges are to identify loci that might have been under selection and to determine the type of natural selection that has influenced their evolutionary history (59). In the field of infectious diseases, site-specific inferences regarding positive selection on loci involved in drug resistance (19) or in the interaction with the host immune system have been proposed as complemen...

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