Protection against Clostridioides difficile disease by a naturally avirulent C. difficile strain.

Clostridioides difficile (C. difficile) strains belonging to the epidemic BI/NAP1/027 (RT027) group have been associated with increased transmissibility and disease severity. In addition to the major toxin A and toxin B virulence factors, RT027 strains also encode the CDT binary toxin. Our lab previously identified a toxigenic RT027 isolate, ST1-75, that is avirulent in mice despite densely colonizing the colon. Here, we show that coinfecting mice with the avirulent ST1-75 and virulent R20291 strains protects mice from colitis due to rapid clearance of the virulent strain and persistence of the avirulent strain. Although avirulence of ST1-75 is due to a mutation in the cdtR gene, which encodes a response regulator that modulates the production of all three C. difficile toxins, the ability of ST1-75 to protect against acute colitis is not directly attributable to the cdtR mutation. Metabolomic analyses indicate that the ST1-75 strain depletes amino acids more rapidly than the R20291 strain and supplementation with amino acids ablates ST1-75's competitive advantage, suggesting that the ST1-75 strain limits the growth of virulent R20291 bacteria by amino acid depletion. Since the germination kinetics and sensitivity to the co-germinant glycine are similar for the ST1-75 and R20291 strains, our results identify the rapidity of in vivo nutrient depletion as a mechanism providing strain-specific, virulence-independent competitive advantages to different BI/NAP1/027 strains. They also suggest that the ST1-75 strain may, as a biotherapeutic agent, enhance resistance to CDI in high-risk patients.

Comprehensive analyses of a large human gut Bacteroidales culture collection reveal species and strain level diversity and evolution.

Species of the Bacteroidales order are among the most abundant and stable bacterial members of the human gut microbiome with diverse impacts on human health. While Bacteroidales strains and species are genomically and functionally diverse, order-wide comparative analyses are lacking. We cultured and sequenced the genomes of 408 Bacteroidales isolates from healthy human donors representing nine genera and 35 species and performed comparative genomic, gene-specific, mobile gene, and metabolomic analyses. Families, genera, and species could be grouped based on many distinctive features. However, we also show extensive DNA transfer between diverse families, allowing for shared traits and strain evolution. Inter- and intra-specific diversity is also apparent in the metabolomic profiling studies. This highly characterized and diverse Bacteroidales culture collection with strain-resolved genomic and metabolomic analyses can serve as a resource to facilitate informed selection of strains for microbiome reconstitution.

Assessing Challenges of 2D-Molybdenum Ditelluride for Efficient Hydrogen Generation in a Full-Scale Proton Exchange Membrane (PEM) Water Electrolyzer.

Proton exchange membrane (PEM) water electrolyzers are critical enablers for sustainable green hydrogen production due to their high efficiency. However, nonplatinum catalysts are rarely evaluated under actual electrolyzer operating conditions, limiting knowledge of their feasibility for H2 production at scale. In this work, metallic 1T'-MoTe2 films were synthesized on carbon cloth supports via chemical vapor deposition and tested as cathodes in PEM electrolysis. Initial three-electrode tests revealed that at 100 mA cm-2, the overpotential of 1T'-MoTe2 approached that of leading 1T'-MoS2 systems, confirming its promise as a hydrogen evolution catalyst. However, when tested in a full-scale PEM electrolyzer, 1T'-MoTe2 delivered only 150 mA cm-2 at 2 V, far below expectations. Postelectrolysis analysis revealed an unexpected passivating tellurium layer, likely inhibiting catalytic sites. While initially promising, the unanticipated passivation caused 1T'-MoTe2 to underperform in practice. This highlights the critical need to evaluate emerging electrolyzer catalysts in PEM electrolyzers, revealing limitations of the idealized three-electrode configuration. Moving forward, validation of model systems in actual electrolyzers will be key to identifying robust nonplatinum catalysts for sustainable green hydrogen production.

Dietary- and host-derived metabolites are used by diverse gut bacteria for anaerobic respiration.

Respiratory reductases enable microorganisms to use molecules present in anaerobic ecosystems as energy-generating respiratory electron acceptors. Here we identify three taxonomically distinct families of human gut bacteria (Burkholderiaceae, Eggerthellaceae and Erysipelotrichaceae) that encode large arsenals of tens to hundreds of respiratory-like reductases per genome. Screening species from each family (Sutterella wadsworthensis, Eggerthella lenta and Holdemania filiformis), we discover 22 metabolites used as respiratory electron acceptors in a species-specific manner. Identified reactions transform multiple classes of dietary- and host-derived metabolites, including bioactive molecules resveratrol and itaconate. Products of identified respiratory metabolisms highlight poorly characterized compounds, such as the itaconate-derived 2-methylsuccinate. Reductase substrate profiling defines enzyme-substrate pairs and reveals a complex picture of reductase evolution, providing evidence that reductases with specificities for related cinnamate substrates independently emerged at least four times. These studies thus establish an exceptionally versatile form of anaerobic respiration that directly links microbial energy metabolism to the gut metabolome.

Screening de parametros hemostáticos en adultos y jóvenes influencia del sexo y altitud

En el laboratorio de fisiología de la Facultad de Medicina (Quito- Ecuador) se procedió a determinar los parámetros hemostáticos: tiempo de ssangría, tiempo de coagulación, tiempo de retraccción dle coïgulo: en adultos y jóvenes residnetes a 2.800mts sobre el nivel del mar (Quito) De una muestra de 203 jóvenes adultos en 104 hombres y 99 mujeres, se determinó, el tiempo de sangría (n=93) en 49 hombres y 44 mujeres: el tiempo de coagulación (n=71) en 36 hombres y 35 mujeres, el tiempo de retracción del coágulo (n=39) en 19 hombres y 20 mujeres. Se aplicaron técnicas convencionales para el timpo de sangría, punción a nivel del pulpejo de un dedo, para tiempo de coagulación y tiempo de tretracción del coágulo gota fresca en placa de vidrio. Se encontró que los valores promedios de la población total del tiempo de ssangría, tiempo de coagulación y tiempo de retracción del coagúlo fueron 3:37 más o menos1.85;8.55 más o menos2.76; 44.10 más o menos 12.31 respectivamente. Se observó que los valores de Ts y Tc fueron similares entre ambos sexos en tanto que TCR fue superior en el sexo masculino (p 0.03); sin influencia de los cambios crónicos de la altitud. Los valores de referencia local en adultos jóvenes de ambos sexos residentes a 2820 mts sobre el nivel del mar se muestran simialres con los parámetros de referencia internacional...