Biology subjects

Pinto, Y.

Publications and source records attributed to Pinto, Y..

7 recordsLinked to original sources

bioRxiv2026

Stability of Antibody Repertoires in Astronauts During Long-Term Spaceflight

Long-duration spaceflight is known to disrupt several aspects of immune function yet its impact on the antiviral antibody repertoire remains unclear. We analyzed longitudinal plasma samples from 11 astronauts participating in a 6-month long spaceflight, including preflight, inflight, and postflight timepoints. Using a high-throughput serological method based on phage display of linear peptides from thousands of viruses we assessed the stability of antiviral antibodies over time. Across two phage libraries expressing different pathogen panels, we detected antibodies against Alphainfluenzavirus, Betainfluenzavirus, Enterovirus, and Orthopneumovirus consistently with the highest abundancy in all astronauts over all timepoints. Antibody levels against these infectious agents remained remarkably stable within individuals during and after spaceflight. In contrast, substantial heterogeneity was observed among astronauts, reflecting individualized immune histories and baseline antibody profiles. These results were confirmed by a different immunoassay using whole protein from the most targeted viruses. Together, these findings demonstrate that the antiviral antibody repertoire is largely resilient during prolonged spaceflight, highlighting preserved humoral memory despite potential dysregulation in cellular immune compartments.

immunology↗

bioRxiv2026

A whole organism screening platform identifies gut microbiome microproteins that modulate host metabolism

Advances in metagenomic sequencing over the past two decades have identified vast numbers of previously uncharacterised small open reading frames that may encode microproteins (<50aa). Although computational tools have accelerated gene sequence prediction from metagenomic data, the function of most annotated proteins remains unknown and untested, especially in the context of host-microbiome interactions. Here, we present a scalable phenotypic screening pipeline to identify gut microbiome-derived proteins that modulate host function. Using the nematode worm Caenorhabditis elegans as a whole animal model that is amenable to systematic screening approaches, our pipeline integrates high-throughput cloning, expression and delivery to worms via feeding, followed by behavioural phenomics screening. We apply this approach to a pilot library of 126 uncharacterised microproteins (< 50 aa) from healthy human gut metagenomes, identifying a set of high-interest targets with potential activity and ultimately validating a microprotein that modulates host fatty acid metabolism when expressed. With protein-based therapies increasingly recognised as a promising alternative to traditional small molecules, this work highlights the potential of a target-agnostic approach for the systematic screening and discovery of novel bioactive proteins.

microbiology↗

bioRxiv2025

A genomic atlas of the human gut virome elucidates genetic factors shaping host interactions

Viruses are key modulators of human gut microbiome composition and function. While metagenomic sequencing has enabled culture-independent discovery of gut bacteriophage diversity, existing genomic catalogues suffer from limited geographic representation, sparse taxonomic classification, and insufficient functional annotation, hindering detailed investigation into phage biology. Here, we present the Unified Human Gastrointestinal Virome (UHGV), a collection of 873,994 viral genomes from globally diverse populations that addresses these limitations. UHGV provides high-quality virome references with extensive host predictions, comprehensive functional annotations, protein structures, a classification framework for comparative analysis, and a web portal to facilitate data access. Using UHGV to profile worldwide metagenomes, we found that host range breadth is strongly associated with phage prevalence. Additionally, we identified diversity-generating retroelements and DNA methyltransferases as key factors enabling phage populations to access diverse hosts, revealing how specific genomic features contribute to global phage distribution patterns. UHGV is available at http://uhgv.jgi.doe.gov.

genomics↗

bioRxiv2025

Nutrition-dependent development of the Oral Microbiome in Early Pregnancy

BackgroundMost studies of the oral microbiome during pregnancy have focused on the second and third trimesters (T2, T3, respectively). Findings remain inconsistent-some report shifts in specific taxa, whereas others observe little change in diversity. To date, no large-scale longitudinal study has examined oral microbiome development across all three trimesters, leaving early gestational dynamics (during the first trimester; T1) largely unexplored. MethodsWe conducted a longitudinal analysis of the oral microbiome in 346 pregnant women from Israel and validated key findings in an independent cohort of 154 pregnant women from Russia. In Israel, saliva samples were collected during T1 (11-14 weeks), T2 (24-28 weeks), and T3 (32-38 weeks) trimesters; in Russia, samples were collected during T2 and T3 with similar ranges of gestational weeks. Alongside sample collection, participants completed dietary and health questionnaires to assess maternal factors that could influence microbial composition. Microbial profiles were analyzed to test for (i) differential abundance across trimesters and (ii) the influence of maternal nutrition and lifestyle factors on these dynamics. ResultsSignificant shifts in oral microbial composition were observed as early as the transition from T1 to T2. Alpha diversity decreased progressively across pregnancy (Shannon index: T1 = 3.261, T2 = 3.173, T3 = 3.109; Kruskal-Wallis p = 0.0023). Notable taxonomic changes included a significant reduction in Verrucomicrobiota (particularly Akkermansia muciniphila) and an increase in Synergistota from T1 to T2 (adjusted p < 0.01), alongside an increase in Gammaproteobacteria and a decrease in Erysipelotrichia, suggesting an ecological shift towards potentially pro-inflammatory communities. Despite these systematic population-level changes, within-subject microbial distances across trimesters were smaller than between-subject distances, indicating that individual women maintained relatively stable microbial profiles over time. Among 54 maternal variables examined, gluten-free diet showed the strongest and most consistent associations with oral microbiome composition across all trimesters, followed by smoking history and conception method. Key findings were validated in an independent cohort of 154 Russian women. ConclusionsThis study provides the first large-scale evidence of significant oral microbiome changes beginning in early pregnancy, characterized by reduced diversity and a directional shift toward potentially pro-inflammatory communities. The strong associations with gluten consumption and smoking suggest a large-scale effect of lifestyle on the pregnancy oral microbiome. The alteration in the microbial composition highlights the oral microbiome as a sensitive marker of gestational physiology.

microbiology↗

bioRxiv2024

Dual quorum-sensing control of purine biosynthesis drives pathogenic fitness of Enterococcus faecalis

Enterococcus faecalis is a resident of the human gut, though upon translocation to the blood or body tissues, it can be pathogenic. Here we discover and characterize two peptide-based quorum-sensing systems that transcriptionally modulate de novo purine biosynthesis in E. faecalis. Using a comparative genomic analysis, we find that most enterococcal species do not encode this system; E. moraviensis, E. haemoperoxidus and E. caccae, three species that are closely related to E. faecalis, encode one of the two systems, and only E. faecalis encodes both systems. We show that these systems are important for the intracellular survival of E. faecalis within macrophages and for the fitness of E. faecalis in a murine wound infection model. Taken together, we combine comparative genomics, microbiological, bacterial genetics, transcriptomics, targeted proteomics and animal model experiments to describe a paired quorum sensing mechanism that directly influences central metabolism and impacts the pathogenicity of E. faecalis.

microbiology↗

bioRxiv2022

Phanta: Phage-inclusive profiling of human gut metagenomes

The human gut microbiome is a diverse ecosystem that encompasses multiple domains of life and plays a vital role in human health. Due to technical limitations, most microbiome studies have focused on gut prokaryotes, overlooking bacteriophages and other gut viruses. The most common method to profile viruses is to assemble shotgun metagenomic reads - often from virus-enriched samples - and identify viral genomes de novo. While valuable, this resource-intensive and reference-independent method has limited sensitivity. To overcome these drawbacks, we developed Phanta, which profiles human gut metagenomes in a virus-inclusive manner directly from short reads utilizing recently published catalogs of gut viral genomes. Phanta incorporates k-mer based classification tools and was developed with virus-specific properties in mind. Specifically, it includes optimizations considering viruses small genome size, sequence homology with prokaryotes, and interactions with other members of the gut microbial community. Based on simulations, the workflow is fast and accurate with respect to both prokaryotes and viruses, minimizing false positive species identification using a novel genome coverage-based strategy. When applied to metagenomes from healthy adults, Phanta identified ~200 viral species per sample, ~5x more than the standard assembly-based methods. Notably, we observed a 2:1 ratio between gut viruses and bacteria, with higher interindividual variability of the gut virome compared to the gut bacteriome. Phanta performs equally well on bulk vs. virus-enriched metagenomes, making it possible to study prokaryotes and viruses in a single experiment, with a single analysis. Phanta can tandemly profile gut viruses and prokaryotes in existing and novel datasets, and can therefore identify cross-domain interactions with likely relevance to human health. We expect that Phanta will reduce the barrier to virus-inclusive studies of the human gut microbiome, thus making it standard practice.

genomics↗

bioRxiv2021

A screen of covalent inhibitors in Mycobacterium tuberculosis identifies serine hydrolases involved in lipid metabolism as potential therapeutic targets

The increasing incidence of antibiotic-resistant Mycobacterium tuberculosis infections is a global health threat necessitating the development of new antibiotics. Serine hydrolases (SHs) are a promising class of targets because of their importance for the synthesis of the mycobacterial cell envelope. We screened a library of small molecules containing serine-reactive electrophiles and identified narrow spectrum inhibitors of M. tuberculous growth. Using these lead molecules, we performed competitive activity-based protein profiling and identified multiple SH targets, including enzymes with uncharacterized functions. Lipidomic analyses of compound-treated cultures revealed an accumulation of free lipids and a substantial decrease in lipooligosaccharides, linking SH inhibition to defects in cell envelope biogenesis. Mutant analysis revealed a path to resistance via the synthesis of mycocerates, but not through mutations to target enzymes. Our results suggest that simultaneous inhibition of multiple SH enzymes is likely to be an effective therapeutic strategy for the treatment of M. tuberculosis infections.

microbiology↗