Biology subjects

Xavier, K. B.

Publications and source records attributed to Xavier, K. B..

9 recordsLinked to original sources

bioRxiv2026

Pervasive bacterial and prophage hybridization during chronic gut inflammation

Inflammatory bowel diseases (IBD) are modulated by microbiota composition, host genetics, and environmental factors1. Humans and other mammals are colonized by multiple strains of Escherichia coli, a species that expands in abundance in IBD patients2. The state of chronic inflammation characteristic of IBD is expected to intensify selective pressures on the gut microbial community, leading to distinct adaptive trajectories among its constituents. Here we couple in vivo experimental evolution with short- and long-read sequencing to test this hypothesis at the level of mutation and horizontal gene transfer (HGT). By colonizing IL10KO mice, a model of IBD3, and healthy wild-type mice with two strains of E. coli, we show that the tempo and mode of evolution are strain-specific and strongly shaped by host inflammatory status. Unique mutations associate with host inflammatory status independently of microbiota composition, and rates of transfer are diagnostic of chronic inflammation. Extensive transduction events occur in the inflamed gut, giving rise to hybrid clones that form a new genetic lineage, one that becomes dominant in this disease context. The high levels of recombination between prophages uncovered here point to a critical role of HGT and viral evolution in IBD.

microbiology↗

bioRxiv2026

Slow to Start, Free at Last: Dual Effects of Mucin on Escherichia coli Phage T4

Bacteriophages traversing the gastrointestinal tract are exposed to extreme physicochemical stresses that may rapidly compromise virion integrity and shape infection dynamics. While some phages bind to host-derived mucins at mucosal surfaces, the functional consequences of soluble mucin glycans for phage-host interactions remain incompletely understood. Here, we show that soluble mucin glycans exert dual effects on the Escherichia coli phage T4 by delaying infection initiation while simultaneously providing environmental virion stability. Mucin-coated T4 exhibits a lag in the onset of productive infection, consistent with transient steric occlusion from E. coli, yet without impairing overall phage progeny production once infection was established. We further show that E. coli can metabolize purified mucin, supporting a model in which dynamic remodeling of the mucin matrix gradually releases T4 and enables infection. Importantly, mucin coating substantially increases T4 survival under gastrointestinal-like stresses, including acidic pH and protease exposure. Moreover, we find that in a murine gut colonization model, a single oral dose of mucin-coated T4 displayed enhanced fecal persistence over a two-week period, which correlated with prolonged suppression of E. coli populations and delayed resolution of phage-associated functional shifts in the gut microbiome. Together, we find that that soluble mucin glycans actively shape T4 phage infection kinetics, virion stability, and ecological impact in the murine gut, and support mucin-based formulations as a strategy to extend the persistence and efficacy of orally delivered phages.

microbiology↗

bioRxiv2024

High-resolution lineage tracking of within-host evolution and strain transmission in a human gut symbiont across ecological scales

Gut bacteria rapidly evolve in vivo, but their long-term success requires dispersal across hosts. Here, we quantify this interplay by tracking >50,000 genomically barcoded lineages of the prevalent commensal Bacteroides thetaiotaomicron (Bt) among co-housed mice. We find that adaptive mutations rapidly spread between hosts, overcoming the natural colonization resistance of resident Bt strains. Daily transmission rates varied >10-fold across hosts, but shared selection pressures drove predictable engraftment of specific lineages over time. The addition of a 49-species community shifted the adaptive landscape relative to mono-colonized Bt without slowing the rate of evolution, and reduced transmission while still allowing specific mutants to engraft. Whole-genome sequencing uncovered diverse modes of adaptation involving complex carbohydrate metabolism. Complementary in vitro evolution across 29 carbon sources revealed variable overlap with in vivo selection pressures, potentially reflecting synergistic and antagonistic pleiotropies. These results show how high-resolution lineage tracking enables quantification of commensal evolution across ecological scales.

evolutionary biology↗

bioRxiv2023

Novel gut probiotic engages microbiota for recovery and pathobiont clearance while preventing inflammation

The microbiota inhabiting the mammalian gut serves as a protective barrier against pathogen invasion through a mechanism known as colonization resistance. Antibiotic treatments can inadvertently disturb the gut microbiota, compromising colonization resistance and increasing hosts susceptible to infections. Non-pneumoniae Klebsiella spp. members of the gut microbiota play a crucial role in colonization resistance and clearance from the gut of pathogenic Enterobacteriaceae following antibiotic-induced perturbations. Specifically, Klebsiella strain ARO112 a gut microbiota isolate, can effectively resist and clear Escherichia coli colonization after antibiotic-induced dysbiosis. We assessed the potential of Klebsiella sp ARO112 to promote clearance of Enterobacteriaceae pathobiont Adherent-Invasive E. coli (AIEC) in an Inflammatory Bowel Disease (IBD) mouse model susceptible to inflammatory episodes. In antibiotic-treated IBD-predisposed mice infected with the AIEC, Klebsiella sp. ARO112 promoted a faster recovery of gut microbiota members potentially involved in butyrate production and accelerated pathobiont clearance. Functionally, ARO112-driven microbiota recovery promoted higher butyrate levels and prevented intestinal inflammation compared to untreated animals. Conversely, treatment with the well-known probiotic E. coli Nissle 1917 enhanced AIEC colonization and inflammation. Furthermore, we assessed the safety of ARO112 as a potential next-generation probiotic; phenotypic comparison of ARO112 against closely related Enterobacteriaceae revealed its lower pathogenic potential, including being more recalcitrant to antibiotic resistance acquisition. Overall, our results showing that Klebsiella sp. ARO112 can resolve infections while contributing to the promotion of intestinal health, underscore its potential as a biotherapy agent that can disrupt inflammation-treatment-infection cycles. This potential extends beyond IBD patients, encompassing individuals with other inflammatory-based conditions related to microbiota imbalances.

microbiology↗

bioRxiv2023

Novel pathways converge with quorum sensing to regulate plant and insect host-specific factors in Erwinia carotovora

Erwinia carotovora Ecc15 is a vector-borne phytopathogen that relies on insects to be transmitted between plant hosts. To interact with its hosts, this bacterium depends on host-specific bacterial traits. Plant tissue maceration depends on production of plant cell wall degrading enzymes (PCWDE), while survival in the digestive tract of the insect requires the Erwinia virulence factor (evf). Evf expression is responsible for the cost of Ecc15 infection in Drosophila melanogaster and overexpression is lethal to the insect host. Therefore, its expression must be well controlled. Expression of evf and PCWDEs is co-regulated by quorum sensing via the transcriptional regulator Hor. Since virulence factors are often controlled by multiple signals, we asked which additional factors regulate evf expression. Using a genetic screen, we identified the sensor histidine kinase arcB and a new TetR-like regulator (named herein as lvtR, after Low Virulence Transcriptional Repressor), as novel regulators not only of evf, but also of pelA, which encodes a major PCWDE. We further demonstrate that arcB and lvtR mutants have reduced plant tissue maceration and reduced development delay and lethality in Drosophila melanogaster, compared to wild-type bacteria. Thus showing the importance of these regulators in the establishment of Erwinia-host-vector interactions. We also found that ArcB and LvtR regulation converges on Hor, independently of quorum sensing, to co-regulate expression of both plant and insect bacterial interaction factors during plant infection. Taken together, our results reveal a novel regulatory hub that enables Ecc15 to integrate quorum sensing responses and environmental cues to co-regulate traits required for infection of both the plant and the insect vector. Moreover, we show that ArcB regulation of bacteria-host interaction processes is conserved in other bacteria. Author SummaryVector-borne pathogens depend on continuous cycles of replication and transmission between hosts and vectors, requiring multiple factors to interact with each of the hosts. The expression of these multiple interaction factors can be very costly, so it is expected that regulation of virulence has been evolutionarily tuned to produce expressions patterns that minimize the cost of establishing the infection while maximizing transmission efficiency of the pathogen. Here, we investigate the tripartite interaction between Ecc15, a plant and an insect, and show that quorum sensing, a widely conserved sensory regulator arcB and a regulator of previously unknown function, lvtR, converge to simultaneously co-regulate the expression of bacterial factors required for these interactions. Gene expression regulation is channeled through the conserved regulator Hor, which serves as a molecular hub for the integration of these multiple signals. Our data suggest that integration of multiple signals to co-regulate plant and insect associated factors ensure fine-tune titration of gene expression and maximization of bacterial energetic resources.

microbiology↗

bioRxiv2020

Quantifying the interplay between rapid bacterial evolution within the mouse intestine and transmission between hosts

Due to limitations on high-resolution strain tracking, selection dynamics during gut-microbiota colonization and transmission between hosts remain mostly mysterious. Here, we introduced hundreds of barcoded Escherichia coli strains into germ-free mice and quantified strain-level dynamics and metagenomic changes. Mutants involved in motility and utilization of abundant metabolites were reproducibly selected within days. Even with rapid selection, coprophagy enforced similar barcode distributions across co-housed mice. Whole-genome sequencing of hundreds of isolates quantified evolutionary dynamics and revealed linked alleles. A population-genetics model predicted substantial fitness advantages for certain mutants and that migration accounted for ~10% of the resident microbiota each day. Treatment with ciprofloxacin demonstrated the interplay between selection and transmission. While initial colonization was mostly uniform, in two mice a bottleneck reduced diversity and selected for ciprofloxacin resistance in the absence of drug. These findings highlight the interplay between environmental transmission and rapid, deterministic selection during evolution of the intestinal microbiota.

microbiology↗

bioRxiv2019

Quorum sensing regulation in Erwinia carotovora affects development of Drosophila melanogaster infected larvae

Multi-host bacteria must rapidly adapt to drastic environmental changes, relying on integration of multiple stimuli for an optimal genetic response. Erwinia spp. are phytopathogens that cause soft-rot disease in plants. Erwinia carotovora Ecc15 is used as a model for bacterial oral-route infection in Drosophila melanogaster as it harbors a gene, the Erwinia virulence factor (Evf), which has been previously shown to be a major determinant for infection of D. melanogaster gut. However, the factors involved in regulation of evf expression are poorly understood. We investigated whether evf could be controlled by quorum sensing since, in the Erwinia genus, quorum sensing regulates pectolytic enzymes, the major virulence factors needed to infect plants. Here, we show that transcription of evf is positively regulated by quorum sensing in Ecc15 via the acyl-homoserine lactone (AHL) signal synthase ExpI, and the AHL receptors ExpR1 and ExpR2. Moreover, we demonstrate that the GacS/A two-component system is partially required for evf expression. We also show that the load of Ecc15 in the gut depends upon the quorum sensing-mediated regulation of evf. Furthermore, we demonstrate that larvae infected with Ecc15 suffer a developmental delay as a direct consequence of the regulation of evf via quorum sensing. Overall, our results show that Ecc15 relies on quorum sensing to control production of both pectolytic enzymes and Evf. This regulation influences the interaction of Ecc15 with its two known hosts, indicating that quorum sensing and GacS/A signaling systems may impact bacterial dissemination via insect vectors that feed on rotting plants. SignificanceIntegration of genetic networks allows bacteria to rapidly adapt to changing environments. This is particularly important in bacteria that interact with multiple hosts. Erwinia carotovora Ecc15 is a plant pathogen that uses Drosophila melanogaster as a vector. To interact with these two hosts, Ecc15 uses two different sets of virulence factors: plant cell wall-degrading enzymes to infect plants and the Erwinia virulence factor (evf) to infect Drosophila. Our work shows that, despite the virulence factors being different, both are regulated by homoserine lactone quorum sensing and the two component GacS/A system. Moreover, we show that these pathways are essential for Ecc15 loads in the gut of Drosophila and that this interaction carries a cost to the vector in the form of a developmental delay. Our findings provide evidence for the importance of quorum sensing regulation in the establishment of multi-host interactions.

microbiology↗

bioRxiv2019

Recovery of the gut microbiota after antibiotics depends on host diet and environmental reservoirs

That antibiotics alter microbiota composition and increase infection susceptibility is well known, but their generalizable effects on the gut commensal community and dependence on environmental variables remain open questions. Here, we systematically compared antibiotic responses in gnotobiotic and conventional mice across antibiotics, microbiotas, diets, and housing status. We identify remarkable resilience, whereby a humanized microbiota recovers before drug administration ends, with transient dominance of resistant Bacteroides and taxa-asymmetric reduction in diversity. In other cases, in vitro sensitivities were not predictive of in vivo responses, underscoring the significance of host and community contexts. A fiber-deficient diet exacerbated collapse of the microbiota and delayed recovery, despite the presence of a similar core community across diets at the point of maximal disturbance. Resilience to a second ciprofloxacin treatment was observed via response reprogramming, in which species replacement after ciprofloxacin treatment established resilience to a second treatment, and also through cross housing transmission. Single-housing drastically disrupted recovery, highlighting the importance of environmental microbial reservoirs and suggesting sanitation may exacerbate the duration of antibiotic-mediated disruption. Our findings highlight the ability of the commensal microbiota to deterministically adapt to large perturbations, and the translational potential for modulating diet, sanitation, and microbiota composition during antibiotics.

microbiology↗

bioRxiv2017

Cheating on orthogonal social traits prevents the tragedy of the commons in Pseudomonas aeruginosa

Bacterial cooperation can be disrupted by non-producers, which can profit from public goods without paying their production cost. A cheater can increase in frequency, exhausting the public good and causing a population collapse. Here we investigate how interactions among two cheaters for distinct social traits influence the short and long-term dynamics of polymorphic populations. Using as a model Pseudomonas aeruginosa and its extensively studied social traits, production of the siderophore pyoverdine and the quorum sensing regulated elastase, we analyzed the social dynamics of polymorphic populations under conditions where the two traits are required for optimal growth. We show that cheaters for either trait compete with both the wild type and each other, and that mutants for pyoverdine production can prevent a drastic population collapse caused by quorum sensing cheaters. A simple mathematical model suggests that the observed social dynamics are determined by the ratio of the costs of each social trait, such that the mutant which avoids paying the highest cost dominates the population. Finally, we demonstrate how quorum sensing regulation can avoid the full loss of cooperation.

genomics↗