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Genome sequencing has reinvigorated the infectious disease research field, shedding light on disease epidemiology, pathogenesis, host–pathogen interactions and also evolutionary processes exerted upon pathogens. Mycobacterium tuberculosis complex (MTBC), enclosing M. bovis as one of its animal-adapted members causing tuberculosis (TB) in terrestrial mammals, is a paradigmatic model of bacterial evolution. As other MTBC members, M. bovis is postulated as a strictly clonal, slowly evolving pathogen, with apparently no signs of recombination or horizontal gene transfer. In this work, we applied comparative genomics to a whole genome sequence (WGS) dataset composed by 70 M . bovis from different lineages (European and African) to gain insights into the evolutionary forces that shape genetic diversification in M. bovis . Three distinct approaches were used to estimate signs of recombination. Globally, a small number of recombinant events was identified and confirmed by two independent methods with solid support. Still, recombination reveals a weaker effect on M. bovis diversity compared with mutation (overall r/m = 0.037). The differential r/m average values obtained across the clonal complexes of M. bovis in our dataset are consistent with the general notion that the extent of recombination may vary widely among lineages assigned to the same taxonomical species. Based on this work, recombination in M. bovis cannot be excluded and should thus be a topic of further effort in future comparative genomics studies for which WGS of large datasets from different epidemiological scenarios across the world is crucial. A smaller M. bovis dataset ( n  = 42) from a multi-host TB endemic scenario was then subjected to additional analyses, with the identification of more than 1,800 sites wherein at least one strain showed a single nucleotide polymorphism (SNP). The majority (87.1%) was located in coding regions, with the global ratio of non-synonymous upon synonymous alterations (dN/dS) exceeding 1.5, suggesting that positive selection is an important evolutionary force exerted upon M. bovis . A higher percentage of SNPs was detected in genes enriched into “lipid metabolism”, “cell wall and cell processes” and “intermediary metabolism and respiration” functional categories, revealing their underlying importance in M. bovis biology and evolution. A closer look on genes prone to horizontal gene transfer in the MTBC ancestor and included in the 3R (DNA repair, replication and recombination) system revealed a global average negative value for Taijima’s D neutrality test, suggesting that past selective sweeps and population expansion after a recent bottleneck remain as major evolutionary drivers of the obligatory pathogen M. bovis in its struggle with the host.

Introduction: Very low-calorie diets with hospitalization have demonstrated promise as a viable therapeutic option for severe obesity and its associated comorbidities. However, large studies providing a comprehensive longitudinal observation of patients undergoing this therapy are lacking. We evaluated the effectiveness of treating severe obesity in hospitalized patients, using very low-calorie diets and clinical support to develop lifestyle changes. Methods: This study was a retrospective cohort comparing exposure variables in a secondary data analysis with a pre-post treatment design. Data were obtained from medical records of patients with severe obesity (grade II or III) treated in a Brazilian obesity specialist hospital from 2016 to 2022. The patients underwent a very low-calorie diet (500–800 kCal/day) and immersive changes in lifestyle habits, monitored by a multidisciplinary team. At 3 months, 777 patients presented complete data and 402 presented complete data at 6 months. The study compared changes in bioimpedance and laboratory tests, between men and women and age groups. Results: Three months of hospitalization yielded significant reductions in weight, body mass index (BMI), body fat, skeletal muscle mass, glucose, inflammatory, and lipid parameters. These reductions were more pronounced after 6 months, nearly doubling those observed at 3 months. In women, BMI and fat mass reduced by 10.4% and 15.2% at 3 months and 20.4% and 31.3% at 6 months, respectively. In men, BMI and fat mass decreased by 12.9% and 25.3 at 3 months and 23.6% and 45.3% at 6 months, respectively. Elderly individuals (aged ≥ 60 years) had smaller reductions in BMI and fat mass than non-elderly individuals (aged < 60 years) but still presented significant improvements. Conclusion: This study suggests the viability of treating severe obesity by hospitalization with low-calorie diets and immersive lifestyle changes. This treatment modality significantly improves anthropometric measurements, glucose, lipids, and inflammatory markers, thereby reducing cardiovascular risk.

Animal tuberculosis (TB) remains a serious concern for animal and human health. circulates in multi-host systems, dominated by the European 2 clonal complex (Eu2) in Iberia. In this work, we use genomic epidemiology to infer the emergence, spread, and spatiotemporal patterns of Eu2 in the official epidemiological risk area of animal TB in Portugal. Phylogenetic analysis of 144 whole-genome sequences from cattle, wild boar, and red deer, representing the 2002-2021 period, distinguished three Eu2 clades that evolved independently. The major Eu2 clade underwent phylodynamic inferences to estimate the time and location of outbreaks, host transitions, and spatial diffusion as well. The origin of this Eu2 clade was attributed to the red deer population in the Castelo Branco district, near the border with Spain. Most host transitions were intraspecific (80%), while interspecific transmissions between wildlife species (wild boar-red deer), and between wild boar and cattle, were highly supported. Phylogeographic reconstruction evidenced that most transitions (82%) occur within municipalities, highlighting local transmission corridors.Our study indicates that continues to spread at the cattle-wildlife interface within the animal TB hotspot area, possibly driven by the foraging behaviour of wild boar near agricultural lands. Red deer seems to be an important driver of TB within wildlife hosts, while the wild boar links the multi-host wildlife community and livestock. This work highlights the value of combining genomic epidemiology with phylodynamic inference to resolve host jumps and spatial patterns of , providing real-time clues about points of intervention.

Non-tuberculous mycobacteria (NTM) are paradigmatic colonizers of the total environment, circulating at the interfaces of the atmosphere, lithosphere, hydrosphere, biosphere, and anthroposphere. Their striking adaptive ecology on the interconnection of multiple spheres results from the combination of several biological features related to their exclusive hydrophobic and lipid-rich impermeable cell wall, transcriptional regulation signatures, biofilm phenotype, and symbiosis with protozoa. This unique blend of traits is reviewed in this work, with highlights to the prodigious plasticity and persistence hallmarks of NTM in a wide diversity of environments, from extreme natural milieus to microniches in the human body. Knowledge on the taxonomy, evolution, and functional diversity of NTM is updated, as well as the molecular and physiological bases for environmental adaptation, tolerance to xenobiotics, and infection biology in the human and non-human host. The complex interplay between individual, species-specific and ecological niche traits contributing to NTM resilience across ecosystems are also explored. This work hinges current understandings of NTM, approaching their biology and heterogeneity from several angles and reinforcing the complexity of these microorganisms often associated with a multiplicity of diseases, including pulmonary, soft-tissue, or milliary. In addition to emphasizing the cornerstones of knowledge involving these bacteria, we identify research gaps that need to be addressed, stressing out the need for decision-makers to recognize NTM infection as a public health issue that has to be tackled, especially when considering an increasingly susceptible elderly and immunocompromised population in developed countries, as well as in low- or middle-income countries, where NTM infections are still highly misdiagnosed and neglected.

Livestock production is a fundamental pillar of the Moroccan economy. Infectious diseases of cattle and other species represent a significant threat to the livestock industry, animal health, and food safety. Bovine tuberculosis (bTB), mainly caused by Mycobacterium bovis , generates considerable direct and indirect economic losses, and an underestimated human health burden caused by zoonotic transmission. Previous studies have suggested likely M. bovis transmission links between Morocco and Southern Europe, however, limitations inherent with the methods used prevented definitive conclusions. In this study, we employed whole genome sequencing analysis to determine the genetic diversity of the first 55 M. bovis whole-genomes in Morocco and to better define the phylogenetic links between strains from Morocco and a large dataset from related and neighboring countries. With a total of 780 M. bovis sequences extracted from cattle, wildlife or humans and representing 36 countries, we discovered two new M bovis spoligotypes in Morocco and that the Moroccan clonal complexes are classified as belonging to Europe or Unknown, supporting previous studies that the Sahara Desert might be playing a key role in preventing M. bovis transmission between North Africa and Sub-Saharan Africa. Furthermore, our analysis showed a close M. bovis genetic relationship between cattle from Morocco and cattle from Spain, France, Portugal and Germany, and from cattle in Morocco and humans in Italy, Germany, and the UK. These results suggest that animal trade and human migration between Morocco and these countries might be playing a role in disease transmission. Our study benefits from a large sample size and a rich dataset that includes sequences from cattle, wildlife and humans from Morocco and neighboring countries, enabling the delineation of M. bovis genetic links across countries and host-species. Our study calls for further investigation of animal and zoonotic TB spread in Morocco and in other countries, which is important to inform future TB control measures at the animal-human interface.

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Background Microbial communities recurrently establish metabolic associations resulting in increased fitness and ability to perform complex tasks, such as xenobiotic degradation. In a previous study, we have described a sulfonamide-degrading consortium consisting of a novel low-abundant actinobacterium, named strain GP, and Achromobacter denitrificans PR1. However, we found that strain GP was unable to grow independently and could not be further purified. Results Previous studies suggested that strain GP might represent a new putative species within the Leucobacter genus (16S rRNA gene similarity < 97%). In this study, we found that average nucleotide identity (ANI) with other Leucobacter spp. ranged between 76.8 and 82.1%, further corroborating the affiliation of strain GP to a new provisional species. The average amino acid identity (AAI) and percentage of conserved genes (POCP) values were near the lower edge of the genus delimitation thresholds (65 and 55%, respectively). Phylogenetic analysis of core genes between strain GP and Leucobacter spp. corroborated these findings. Comparative genomic analysis indicates that strain GP may have lost genes related to tetrapyrrole biosynthesis and thiol transporters, both crucial for the correct assembly of cytochromes and aerobic growth. However, supplying exogenous heme and catalase was insufficient to abolish the dependent phenotype. The actinobacterium harbors at least two copies of a novel genetic element containing a sulfonamide monooxygenase ( sad A) flanked by a single IS1380 family transposase. Additionally, two homologs of sad B (4-aminophenol monooxygenase) were identified in the metagenome-assembled draft genome of strain GP, but these were not located in the vicinity of sad A nor of mobile or integrative elements. Conclusions Comparative genomics of the genus Leucobacter suggested the absence of some genes encoding for important metabolic traits in strain GP. Nevertheless, although media and culture conditions were tailored to supply its potential metabolic needs, these conditions were insufficient to isolate the PR1-dependent actinobacterium further. This study gives important insights regarding strain GP metabolism; however, gene expression and functional studies are necessary to characterize and further isolate strain GP. Based on our data, we propose to classify strain GP in a provisional new species within the genus Leucobacter , ‘ Candidatus Leucobacter sulfamidivorax‘.

Classical molecular analyses of Mycobacterium bovis based on spoligotyping and Variable Number Tandem Repeat (MIRU-VNTR) brought the first insights into the epidemiology of animal tuberculosis (TB) in Portugal, showing high genotypic diversity of circulating strains that mostly cluster within the European 2 clonal complex. Previous surveillance provided valuable information on the prevalence and spatial occurrence of TB and highlighted prevalent genotypes in areas where livestock and wild ungulates are sympatric. However, links at the wildlife–livestock interfaces were established mainly via classical genotype associations. Here, we apply whole genome sequencing (WGS) to cattle, red deer and wild boar isolates to reconstruct the M. bovis population structure in a multi-host, multi-region disease system and to explore links at a fine genomic scale between M. bovis from wildlife hosts and cattle. Whole genome sequences of 44 representative M. bovis isolates, obtained between 2003 and 2015 from three TB hotspots, were compared through single nucleotide polymorphism (SNP) variant calling analyses. Consistent with previous results combining classical genotyping with Bayesian population admixture modelling, SNP-based phylogenies support the branching of this M. bovis population into five genetic clades, three with apparent geographic specificities, as well as the establishment of an SNP catalogue specific to each clade, which may be explored in the future as phylogenetic markers. The core genome alignment of SNPs was integrated within a spatiotemporal metadata framework to further structure this M. bovis population by host species and TB hotspots, providing a baseline for network analyses in different epidemiological and disease control contexts. WGS of M. bovis isolates from Portugal is reported for the first time in this pilot study, refining the spatiotemporal context of TB at the wildlife–livestock interface and providing further support to the key role of red deer and wild boar on disease maintenance. The SNP diversity observed within this dataset supports the natural circulation of M. bovis for a long time period, as well as multiple introduction events of the pathogen in this Iberian multi-host system.

This article aimed to review the role of cytokines, chemokines, growth factors and cellular adhesion molecules as biomarkers for vesicoureteral reflux (VUR) and reflux nephropathy (RN). We reviewed articles from 1979 onward by searching PubMed and Scopus utilizing the combination of words: ‘VUR’ or ‘RN’ and each one of the biomarkers. Genetic, inflammatory, fibrogenic, environmental and epigenetic factors responsible for renal scarring need to be better understood. TGF-β, IL-10, IL-6, IL-8 and TNF seem to exert a role in VUR particularly in RN based on the current literature. Serum levels of procalcitonin have been also associated with high-grade VUR and RN. These molecules should be more intensively evaluated as potential biomarkers for renal scarring in VUR. Further studies are necessary to define which molecules will really be of utility in clinical decisions and as therapeutic targets for VUR and RN.

Animal tuberculosis (TB), caused by Mycobacterium bovis , is maintained in Portugal in a multi-host system, with cattle, red deer and wild boar, playing a central role. However, the ecological processes driving transmission are not understood. The main aim of this study was thus to contribute to the reconstruction of the spatiotemporal history of animal TB and to refine knowledge on M. bovis population structure in order to inform novel intervention strategies. A collection of 948 M. bovis isolates obtained during long-term surveillance (2002–2016, 15 years) of cattle ( n  = 384), red deer ( n  = 303) and wild boar ( n  = 261), from the main TB hotspot areas, was characterized by spoligotyping and 8 to 12- loci MIRU-VNTR. Spoligotyping identified 64 profiles and MIRU-VNTR distinguished 2 to 36 subtypes within each spoligotype, enabling differentiation of mixed or clonal populations. Common genotypic profiles within and among livestock and wildlife in the same spatiotemporal context highlighted epidemiological links across hosts and regions, as for example the SB0119-M205 genotype shared by cattle in Beja district or SB0121-M34 shared by the three hosts in Castelo Branco and Beja districts. These genomic data, together with metadata, were integrated in a Bayesian inference framework, identifying five ancestral M. bovis populations. The phylogeographic segregation of M. bovis in specific areas of Portugal where the disease persists locally is postulated. Concurrently, robust statistics indicates an association of the most probable ancient population with cattle and Beja, providing a clue on the origin of animal TB epidemics. This relationship was further confirmed through a multinomial probability model that assessed the influence of host species on spatiotemporal clustering. Two significant clusters were identified, one that persisted between 2004 and 2010, in Beja district, with Barrancos county at the centre, overlapping the central TB core area of the Iberian Peninsula, and highlighting a significant higher risk associated to cattle. The second cluster was predominant in the 2012–2016 period, holding the county Rosmaninhal at the centre, in Castelo Branco district, for which wild boar contributed the most in relative risk. These results provide novel quantitative insights beyond empirical perceptions, that may inform adaptive TB control choices in different regions.