Molecular and reaction fingerprints are widely used as static descriptors, but their relationship to graph-level reaction application remains unclear. We address this question in counted Extended-Connectivity Fingerprint (ECFP) space, representing reactions as signed differences between product and substrate fingerprints. We define ECFP-compatible templates, for which graph-level reaction application induces a constant fingerprint displacement, yielding a functorial mapping from graph transformations to affine translations in fingerprint space. We also introduce reaction-center ECFPs to encode the local environments required for template application and to provide a fast coordinate-wise prefilter for graph-level reaction applicability. We evaluate this framework on USPTO-50k and MetaNetX reactions across a range of ECFP radii. Both representations carry predictive information for reaction-class and enzyme-class classification, with reaction-center ECFPs contributing information not captured by reaction ECFPs alone. This framework connects reaction templates and reaction fingerprints to molecular pathway search and reaction-property prediction in fingerprint space. We give a formal criterion under which graph-level reaction template application corresponds exactly to a constant translation in counted ECFP space, yielding a functorial map from graph transformations to affine translations. We introduce reaction-center ECFPs, encoding the local environments a reaction requires, which give an O(d) necessary condition for applicability in place of subgraph-isomorphism prefiltering. On USPTO-50k and MetaNetX, this representation carries predictive signal complementary to standard reaction fingerprints for reaction-class and EC-number prediction.
We investigated the adaptation of the aerotolerant Campylobacter jejuni Bf strain to conditions mimicking the poultry slaughter process. We showed that C. jejuni Bf survives and actively multiplies under combined thermal and oxidative stress. Stress exposure induces cell rounding, loss of motility, remodeling of membrane composition, decreased membrane fluidity, and metabolic reprogramming with increased intracellular ATP levels. While maintaining the lipid composition of its plasma membrane, C. jejuni modulates the lipid composition of its extracellular vesicles when exposed to stress. Notably, stressed C. jejuni cells release extracellular vesicles with increased toxicity toward the epithelial barrier of Caco-2 cells, potentially facilitating invasion of the gut epithelium.IMPORTANCECampylobacter infections are one of the leading causes of foodborne gastroenteritis worldwide. Campylobacter readily enters the food chain and is transmitted to humans, primarily through the consumption of contaminated poultry meat. The high prevalence of aerotolerant human Campylobacter jejuni isolates suggests a correlation between their ability to survive under aerobic conditions, virulence, and resistance to harsh stress conditions. However, the underlying mechanism remains unclear. Our results show that C. jejuni extracellular vesicles are part of a survival strategy that links environmental adaptation with pathogenicity.
Lsr2-like xenogeneic silencers are widespread nucleoid-associated proteins in Actinomycetota and are encoded by diverse bacteriophages. However, their roles during bacteriophage infection, one of the most direct encounters with foreign DNA, remain unexplored. In Corynebacterium glutamicum, the Lsr2-like protein CgpS is encoded within the mobile genetic element CGP3 and is known to silence transcription of foreign DNA within this region. Here we show that CgpS restricts infection by the AT-rich bacteriophage JeanGrey. Upon phage DNA injection, CgpS binds phage-derived AT-rich sequences and represses early phage gene transcription. This transcriptional bottleneck prevents efficient phage genome replication and delays progression of the viral program. The resulting temporal window enables activation of host stress and defense pathways, including LexA-regulated SOS genes and antiviral systems. Our findings reveal a novel antiviral function for an Lsr2-like silencer and suggest that xenogeneic silencers can act as regulatory barriers that modulate the outcome of phage infection in Actinomycetota.
The Metaproteomics Initiative was officially launched in 2021 to strengthen collaboration, promote knowledge exchange, and support and lead standardization efforts within the growing metaproteomics community. Over the past 5 years, the Initiative has developed into a structured, global network of researchers. It has launched community-driven benchmark studies, helped shape emerging metadata and reporting standards, developed practical guidance and training materials, organized international symposia, and fostered connections across the microbiome research landscape ( https://metaproteomics.org/ ). We outline the Initiative’s organization, activities, achievements, and ongoing efforts, and reflect on how sustained, community-led coordination has shaped the development of metaproteomics as a field. We further position the Grand Metaproteome Challenges as a next step toward coordinated, community-scale biological research, aimed at advancing functional microbiome studies across clinical, industrial, and environmental application domains, and invite engagement from the wider microbiome and omics communities.
Human diet and lifestyle vary widely across cultures, shaping global diversity in gut microbiome composition and function. However, comparable cross-population studies have been limited by methodological heterogeneity. The Human Diets and Microbiome Initiative (THDMI) integrates standardized recruitment, dietary assessment, and shotgun metagenomics across 1,976 participants from the United States, United Kingdom, Spain, Mexico, and Japan to disentangle biological from technical variation. We observed pronounced geographic differences in nutrient intake, food consumption, and microbial composition, with both shared and country-specific taxa linked to diet quality. Sparse canonical correlation and machine-learning analyses revealed that microbiome–diet associations were largely population-specific, with limited cross-country generalization. Strain-level analyses further uncovered significant genomic differentiation of gut microbes, reflecting localized dietary and ecological pressures. Together, these results show that while core microbial responses to healthy eating exist, the structure and function of the human gut microbiome are profoundly shaped by culture, geography, and long-term dietary practices.
