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Kimbrel, Jeffrey

Publications and source records attributed to Kimbrel, Jeffrey.

5 records
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DOE OSTI2024

Toxin-Antitoxin Systems Reflect Community Interactions Through Horizontal Gene Transfer

Bacterial evolution through horizontal gene transfer (HGT) reflects their community interactions. In this way, HGT networks do well at mapping community interactions, but offer little toward controlling them—an important step in the translation of synthetic strains into natural contexts. Toxin–antitoxin (TA) systems serve as ubiquitous and diverse agents of selection; however, their utility is limited by their erratic distribution in hosts. Here we examine the heterogeneous distribution of TAs as a consequence of their mobility. By systematically mapping TA systems across a 10,000 plasmid network, we find HGT communities have unique and predictable TA signatures. We propose these TA signatures arise from plasmid competition and have further potential to signal the degree to which plasmids, hosts, and phage interact. To emphasize these relationships, we construct an HGT network based solely on TA similarity, framing specific selection markers in the broader context of bacterial communities. This work both clarifies the evolution of TA systems and unlocks a common framework for manipulating community interactions through TA compatibility.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Transporter annotations are holding up progress in metabolic modeling

Mechanistic, constraint-based models of microbial isolates or communities are a staple in the metabolic analysis toolbox, but predictions about microbe-microbe and microbe-environment interactions are only as good as the accuracy of transporter annotations. A number of hurdles stand in the way of comprehensive functional assignments for membrane transporters. These include general or non-specific substrate assignments, ambiguity in the localization, directionality and reversibility of a transporter, and the many-to-many mapping of substrates, transporters and genes. In this perspective, we summarize progress in both experimental and computational approaches used to determine the function of transporters and consider paths forward that integrate both. Investment in accurate, high-throughput functional characterization is needed to train the next-generation of predictive tools toward genome-scale metabolic network reconstructions that better predict phenotypes and interactions. More reliable predictions in this domain will benefit fields ranging from personalized medicine to metabolic engineering to microbial ecology.

Casey, John↗
DOE OSTI2023

Dynamic Phaeodactylum tricornutum exometabolites shape surrounding bacterial communities

Summary Roles of different ecological classes of algal exometabolites in regulating microbial community composition are not well understood. Here, we identify exometabolites from the model diatom Phaeodactylum tricornutum and demonstrate their potential to influence bacterial abundances. We profiled exometabolites across a time course of axenic algal growth using liquid chromatography–tandem mass spectrometry. We then investigated growth of 12 bacterial isolates on individual‐identified exometabolites. Lastly, we compared responses of a P. tricornutum ‐adapted enrichment community to additions of two contrasting metabolites: selective growth substrate 4‐hydroxybenzoic acid and putative signaling/facilitator molecule lumichrome. We identified 50 P. tricornutum metabolites and found distinct temporal accumulation patterns. Two exometabolites (of 12 tested) supported growth of distinct subsets of bacterial isolates. While algal exudates and algal presence drove similar changes in community composition compared with controls, exogenous 4‐hydroxybenzoic acid addition promoted increased abundances of taxa that utilized it in isolation, and also revealed the importance of factors relating to algal presence in regulating community composition. This work demonstrates that secretion of selective bacterial growth substrates represents one mechanism by which algal exometabolites can influence bacterial community composition and illustrates how the algal exometabolome has the potential to modulate bacterial communities as a function of algal growth.

4-hydroxybenzoic acid↗
DOE OSTI2022

Multiple Mutations Associated with Emergent Variants Can Be Detected as Low-Frequency Mutations in Early SARS-CoV-2 Pandemic Clinical Samples

Genetic analysis of intra-host viral populations provides unique insight into pre-emergent mutations that may contribute to the genotype of future variants. Clinical samples positive for SARS-CoV-2 collected in California during the first months of the pandemic were sequenced to define the dynamics of mutation emergence as the virus became established in the state. Deep sequencing of 90 nasopharyngeal samples showed that many mutations associated with the establishment of SARS-CoV-2 globally were present at varying frequencies in a majority of the samples, even those collected as the virus was first detected in the US. A subset of mutations that emerged months later in consensus sequences were detected as subconsensus members of intra-host populations. Spike mutations P681H, H655Y, and V1104L were detected prior to emergence in variant genotypes, mutations were detected at multiple positions within the furin cleavage site, and pre-emergent mutations were identified in the nucleocapsid and the envelope genes. Because many of the samples had a very high depth of coverage, a bioinformatics pipeline, “Mappgene”, was established that uses both iVar and LoFreq variant calling to enable identification of very low-frequency variants. This enabled detection of a spike protein deletion present in many samples at low frequency and associated with a variant of concern.

60 APPLIED LIFE SCIENCES↗