Biology subjects

Carasso, S.

Publications and source records attributed to Carasso, S..

4 recordsLinked to original sources

bioRxiv2026

Growth capacity and mortality burden shape microbial persistence under osmotic stress in Bacteroides thetaiotaomicron

Microbial persistence in the gut is central to sustaining beneficial host-microbiota interactions; however, characterizing determinants of persistence in vivo can be challenging due to the complexity of native microbial communities interacting with the host. Here, we used a defined microbial consortium to demonstrate that intrinsic in vitro growth capacity becomes increasingly predictive of in vivo relative abundance as intestinal osmolality increases. In Bacteroides thetaiotaomicron, in vivo abundance was higher than predicted from growth capacity alone, indicating that additional physiological factors contribute to persistence. We identify mortality as one such determinant: adaptation to prolonged osmotic stress markedly reduced cell loss without enhancing growth capacity. This adaptive phenotype was associated with rapid and reversible phase variation in cell surface-associated PUL78/80 rather than fixed de novo mutations, with the PUL78/80-OFF state becoming progressively enriched among surviving cells as mortality increased. Our findings demonstrate that in addition to growth capacity, reduced cell loss can provide a distinct route to microbial persistence during environmental perturbation.

microbiology↗

bioRxiv2025

Bacteriophage-driven DNA inversions shape bacterial functionality and long-term co-existence in Bacteroides fragilis

Bacterial genomic DNA inversions, which govern molecular phase-variations, provide the bacteria with functional plasticity and phenotypic diversity. These targeted rearrangements enable bacteria to respond to environmental challenges, such as bacteriophage predation, evading immune detection or gut colonization. This study investigated the short- and long-term effects of the lytic phage Barc2635 on the functional plasticity of Bacteroides fragilis, a gut commensal. Germ-free mice were colonized with B. fragilis and exposed to Barc2635 to identify genomic alterations driving phenotypic changes. Phage exposure triggered dynamic and prolonged bacterial responses, including significant shifts in phase-variable regions (PVRs), particularly in promoter orientations of polysaccharide biosynthesis loci. These shifts coincided with increased entropy in PVR inversion ratios, reflecting heightened genomic variability. In contrast, B. fragilis in control mice exhibited stable genomic configurations after gut adaptation. The phase-variable Type 1 restriction-modification system, which affects broad gene expression patterns, showed variability in both groups. However, phage-exposed bacteria displayed more restrained variability, suggesting phage-derived selection pressures. Our findings reveal that B. fragilis employs DNA inversions to adapt rapidly to phage exposure and colonization, leveraging genomic variability for resilience. This study emphasizes gut bacterial genomic and phenotypic plasticity upon exposure to the mammalian host and to bacteriophages.

microbiology↗

bioRxiv2023

Inflammation and bacteriophages affect DNA inversion states and functionality of the gut microbiota

Reversible genomic DNA-inversions control expression of numerous bacterial molecules in the human gut, but how this relates to disease remains uncertain. By analyzing metagenomic samples from six human Inflammatory Bowel Disease cohorts combined with mice experimentation, we identified multiple invertible regions where a particular orientation was correlated with disease. These include the promoter of the anti-inflammatory polysaccharide-A (PSA) of Bacteroides fragilis, which is mostly oriented OFF during inflammation but is present in the ON orientation when inflammation is resolved. We further detected increased abundances of B. fragilis-associated bacteriophages in patients with the PSA OFF orientation, and a significant reduction in the frequency of the ON orientation, in the presence of the B. fragilis-associated bacteriophage, thereby altering the bacterial induced immune modulation. Altogether, we reveal dynamic and reversible bacterial phase-variations driven both by bacteriophages and the host inflammatory state, signifying bacterial functional plasticity during inflammation and opening future research avenues.

microbiology↗

bioRxiv2021

Metagenomic analysis reveals the signature of gut microbiota associated with human chronotypes

Patterns of diurnal activity differ substantially between individuals, with early risers and late sleepers being examples of opposite chronotypes. Growing evidence suggests that the late chronotype significantly impacts the risk of developing mood disorders, obesity, diabetes, and other chronic diseases. Despite the vast potential of utilizing chronotype information for precision medicine, those factors that shape chronotypes remain poorly understood. Here, we assessed whether the various chronotypes are associated with different gut microbiome compositions. Using metagenomic sequencing analysis, we established a distinct signature associated with chronotype based on two bacterial genera, Alistipes (elevated in "larks") and Lachnospira (elevated in "owls"). We identified three metabolic pathways associated with the early chronotype, and linked distinct dietary patterns with different chronotypes. Our work demonstrates an association between the gut microbiome and chronotype and may represent the first step towards developing dietary interventions aimed at ameliorating the deleterious health correlates of the late chronotype.

genomics↗