Biology subjects

Pedro, M. F.

Publications and source records attributed to Pedro, M. F..

3 recordsLinked to original sources

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↗

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↗