Biology subjects
Publications and source records attributed to Simoes, R..
Patient-derived xenografts (PDX) are valuable tools to model human disease and test new therapies. Here, we report, for the first time, a PDX model recapitulating the unique characteristics of a VEXAS patient (unique patient number UPN1).
Below-ground carbon transformations represent a natural climate change mitigation solution, but newly-acquired traits adaptive to climate stress may alter microbial climate feedback mechanisms. To better define microbial evolutionary responses to long-term climate warming, we study microorganisms from an ongoing in situ soil warming experiment at the Harvard Forest Long-term Ecological Research (LTER) site where, for over three decades, soils are continuously heated 5 {degrees}C above ambient temperatures. We hypothesize that across generations of chronic warming, genomic signatures within diverse bacterial lineages reflect trait-based adaptations related to growth and carbon utilization. From our bacterial culture collection isolated from experimental heated and control plots, we sequenced genomes representing taxa dominant in soil communities and sensitive to warming, including lineages of Alphaproteobacteria, Actinobacteria, and Betaproteobacteria. We investigated differences in genomic attributes and patterns of functional gene content to identify genomic signatures of adaptation. Comparative pangenomics revealed accessory gene clusters related to central metabolism, competition, and carbon substrate degradation. Overall, genomes from control plots were relatively enriched in carbon and fatty acid metabolism pathways, while genomes from heated plots were relatively enriched in nitrogen metabolism pathways. We also observed differences in global codon usage bias between heated and control genomes, suggesting potential adaptive traits related to growth or growth efficiency. This effect was more varied for organisms with fewer 16S rrn operons, suggesting that these organisms experience different selective pressures on growth efficiency. Together, these data illustrate the emergence of lineage-specific traits as well as common ecological-evolutionary microbial responses to climate change.
Enterotoxigenic Escherichia coli (ETEC) are a genetically diverse pathologic variant of E. coli defined by the production of heat-labile (LT) and/or heat-stable (ST) toxins. ETEC are estimated to cause hundreds of millions of cases of diarrheal illness annually. However, it is not clear that all strains are equally equipped to cause disease and asymptomatic colonization with ETEC is common in low-middle income regions lacking basic sanitation and clean water where ETEC are ubiquitous. Recent molecular epidemiology studies have revealed a significant association between strains which produce EatA, a secreted autotransporter protein, and the development of symptomatic infection. Here, we demonstrate that LT stimulates production of MUC2 mucin by goblet cells in human small intestine, enhancing the protective barrier between pathogens and enterocytes. In contrast, using explants of human small intestine as well as small intestinal enteroids, we show that EatA counters this host defense by engaging and degrading the MUC2 mucin barrier to promote bacterial access to target enterocytes and ultimately toxin delivery suggesting that EatA plays a crucial role in the molecular pathogenesis of ETEC. These findings may inform novel approaches to prevention of the acute diarrheal illness as well as the sequelae associated with ETEC and other pathogens that rely on EatA and similar proteases for efficient interaction with their human hosts.