Biology subjects

Reis, A. C.

Publications and source records attributed to Reis, A. C..

5 recordsLinked to original sources

bioRxiv2024

Activation of bradykinin receptor B1 promotes desensitization of CXCR2 in neutrophils during severe sepsis and contributes to disease progression in mice.

Sepsis is one of the most common causes of death in intensive care units. The overproduction of proinflammatory mediators during severe sepsis leads to desensitization of CXCR2 on neutrophil, compromising their migration capacity. During early sepsis, kinins are released and bind to bradykinin 1 (BDKRB1) and bradykinin 2 (BDKRB2) receptors, however the involvement of these receptors in sepsis is not yet fully understood. This study demonstrated that the absence of BDKRB2 had no major effects compared to WT mice upon sepsis induction by CLP, suggesting that this receptor plays a minor role under these experimental conditions. In contrast, B1-/- mice showed lower mortality and bacterial recovery compared to WT-CLP mice, which was associated with an increased influx of neutrophils into the peritoneal cavity of CLP-B1-/- mice. WT-CLP mice exhibited increased expression of P110{gamma} and decreased expression of CXCR2 in neutrophils, which was partially reversed in CLP-B1-/- mice. Interestingly, local CXCL1 production was not affected by the absence of BDKRB1. In human neutrophils, LPS induced expression of BDKRB1, and antagonism of this receptor was associated with the restoration of neutrophil recruitment capacity upon stimulation with CXCL8. Furthermore, treatment with a BDKRB1 antagonist in combination with imipenem resulted in a significant improvement in mortality compared to animals treated with the antimicrobial agent alone. Our findings demonstrate that BDKRB1 plays an essential role in exacerbating the inflammatory response and CXCR2 desensitization in neutrophils during CLP-induced severe sepsis, highlighting BDKRB1 as a potential target for sepsis treatment. ImportanceSepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Despite advances in understanding its pathophysiology, sepsis remains a leading cause of mortality in intensive care units nowadays. Here we found that B1 receptor contributes to neutrophil migration failure during severe sepsis. Inhibition of B1 improves neutrophil migration and bacterial clearance, making it a valuable therapeutic candidate for the treatment of sepsis. More importantly, treatment with a BDKRB1 antagonist in combination with imipenem resulted in a significant improvement in mortality compared to animals treated with the antimicrobial agent alone. These results highlight B1 as a potential treatment target for sepsis, offering improved modulation of the inflammatory response and synergy with antibiotics. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/590213v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1f0401aorg.highwire.dtl.DTLVardef@ab8eorg.highwire.dtl.DTLVardef@1ff0c26org.highwire.dtl.DTLVardef@176b5aa_HPS_FORMAT_FIGEXP M_FIG BDKRB1 activation contributes to sepsis-induced hyperinflammation: (A) BDKRB1 activation contributes to sepsis-induced hyperinflammation: (A) BDKRB1 plays an essential role in the pathogenesis of sepsis, partly by mediating impaired neutrophil migration during the disease. It exerts its effects in myeloid cells by controlling the activation of P13K{gamma} and the expression of CXCR2. (B) BDKRB1 antagonist decreases cytokine production and increases neutrophil influx into the peritoneal cavity, resulting in a reduction in bacterial recovery, highlighting DALBK as a potential adjuvant treatment for sepsis C_FIG

microbiology↗

bioRxiv2024

Phylogenetic analysis of Mycobacterium bovis Reveals Evidence Of Animal And Zoonotic Tuberculosis Transmission Between Morocco And European Countries

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 and security. Bovine tuberculosis (bTB), mainly caused by Mycobacterium bovis (M. bovis), generates considerable direct and indirect economic losses, in addition to the unknown 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 more definitive conclusions from being drawn. In this study, we employed whole genome sequencing analysis of a large set of M. bovis isolates to better define the phylogenetic links between strains from Morocco and neighboring countries. A total of 780 M. bovis sequences representing 36 countries were included in the study. The results of SNP analysis showed a close genetic relationship between M. bovis from Morocco and each of Spain, France, Portugal and Germany, this is supported by animal trade between Morocco and these countries, in addition to the important human migration from Morocco to Europe and North America. Regarding zoonotic tuberculosis (TB) transmission, we were able to find genetic links between M. bovis isolates from cattle in Morocco and humans in Italy, Germany, and the UK. These results support our hypothesis of significant transmission of M. bovis from cattle to humans, which calls for further investigations of zoonotic TB transmission in Morocco and in other countries. The fact that no M. bovis sequences from North Africa in the present database were classified as AF1 or AF2 clonal complexes suggests that the Sahara might play a role in preventing M. bovis transmission between North Africa and Sub-Saharan Africa. 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 transmission routes within the animal-human interface.

molecular biology↗

bioRxiv2021

Phylogenomics Sheds Light on the population structure of Mycobacterium bovis from a Multi-Host Tuberculosis System

Molecular analyses of Mycobacterium bovis based on spoligotyping and Variable Number Tandem Repeat (MIRU-VNTR) brought 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. The genetic relatedness of M. bovis isolates from cattle and wildlife have also suggested sustained transmission within this multi-host system. However, while previous surveillance highlighted prevalent genotypes in areas where livestock and wild ungulates are sympatric and provided valuable information on the prevalence and spatial occurrence of TB, links at the wildlife-livestock interfaces were established mainly via genotype associations. Therefore, evidence at a local fine scale of transmission events linking wildlife hosts and cattle remains lacking. Here, we explore the advantages of whole genome sequencing (WGS) applied to cattle, red deer and wild boar isolates to reconstruct the evolutionary dynamics of M. bovis and to identify putative pathogen transmission events. 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 geographic specificities, as well as the establishment of a SNPs 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 reconstruct transmission networks, which together with inferred secondary cases, further structured this M. bovis population by host species and geographic location. WGS of M. bovis isolates from Portugal is reported for the first time, refining the spatiotemporal context of transmission events and providing further support to the key role of red deer and wild boar on the persistence of animal TB in this Iberian multi-host system.

genomics↗

bioRxiv2020

The genomes of invasive coral Tubastraea spp. (Dendrophylliidae) as tool for the development of biotechnological solutions

Corals have been attracting huge attention due to the impact of climate change and ocean acidification on reef formation and resilience. Nevertheless, some species like Tubastraea coccinea and T. tagusensis have been spreading very fast replacing the native ones which affect the local environment and decrease biodiversity of corals and other organisms associated with them. Despite some focal efforts to understand the biology of these organisms, they remain understudied at the molecular level. This knowledge gap hinders the development of cost-effective strategies for both conservation and management of invasive species. In this circumstance, it is expected that genome sequencing would provide powerful insights that could lead to better strategies for prevention, management, and control of this and other invasive species. Here, we present three genomes of Tubastraea spp. in one of the most comprehensive biological studies of corals, that includes flow cytometry, karyotyping, transcriptomics, genomics, and phylogeny. The genome of T. tagusensis is organized in 23 chromosomes pairs and has 1.1 Gb, the T. coccinea genome is organized in 22 chromosome pairs and has 806 Mb, and the Tubastraea sp. genome is organized in 21 chromosome pairs and has 795 Mb. The hybrid assembly of T. tagusensis using short and long-reads has a N50 of 227,978 bp, 7,996 contigs and high completeness estimated as 91.6% of BUSCO complete genes, of T. coccinea has a N50 of 66,396 bp, 17,214 contigs and 88.1% of completeness, and of Tubastraea sp. has a N50 of 82,672 bp, 12,922 contigs and also 88.1% of completeness. We inferred that almost half of the genome consists of repetitive elements, mostly interspersed repeats. We provide evidence for exclusive Scleractinia and Tubastraea gene content related to adhesion and immunity. The Tubastraea spp. genomes are a fundamental study which promises to provide insights not only about the genetic basis for the extreme invasiveness of this particular coral genus, but to understand the adaptation flaws of some reef corals in the face of anthropic-induced environmental disturbances. We expect the data generated in this study will foster the development of efficient technologies for the management of coral species, whether invasive or threatened.

evolutionary biology↗

bioRxiv2017

An automated model test system for systematic development and improvement of gene expression models

Gene expression models greatly accelerate the engineering of synthetic metabolic pathways and genetic circuits by predicting sequence-function relationships and reducing trial-and-error experimentation. However, developing models with more accurate predictions is a significant challenge, even though they are essential to engineering complex genetic systems. Here we present a model test system that combines advanced statistics, machine learning, and a database of 9862 characterized genetic systems to automatically quantify model accuracies, accept or reject mechanistic hypotheses, and identify areas for model improvement. We also introduce Model Capacity, a new information theoretic metric that enables correct model comparisons across datasets. We demonstrate the model test system by comparing six models of translation initiation rate, evaluating 100 mechanistic hypotheses, and uncovering new sequence determinants that control protein expression levels. We applied these results to develop a biophysical model of translation initiation rate with significant improvements in accuracy. Automated model test systems will dramatically accelerate the development of gene expression models, and thereby transition synthetic biology into a mature engineering discipline.

synthetic biology↗