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Goodman, A. L.

Publications and source records attributed to Goodman, A. L..

4 recordsLinked to original sources

Niche partitioning by resource size in the gut microbiome

Niche partitioning promotes diversity of the human gut microbiota. However, the molecular basis of resource specialization and niche separation in the gut remains poorly understood. Here we show that structural differences in glycan transporters drive members of the genus Bacteroides, common human gut commensals, to specialize on distinct chain lengths of the same fructan molecule. While species encoding canonical SusCD systems for glycan import -formed by a membrane-embedded barrel capped with a lipoprotein lid- specialized in long-chain fructans, species with smaller lidless transporters, not previously described in Bacteroides, specialized in short-chain fructans. Strikingly, we found that a [~]140-amino acid domain in the SusC barrel is a structural feature that governs substrate preference: deleting it does not impair transport but instead shifts uptake preferences from long-to short-chain fructans. These structural differences predict competitive outcomes in vivo on fructans of varying lengths, suggesting that glycan uptake mechanisms shape ecological niches in the gut and can inform fiber-based dietary interventions. Similar small lidless transporters exist across the Bacteroidota, expanding the paradigm of glycan utilization in this phylum beyond the canonical SusCD architecture.

microbiology↗

Sphingolipid production by gut Bacteroidetes regulates glucose homeostasis

Levels of Bacteroidetes in the gut microbiome are positively associated with insulin resistance (IR) in humans. Considering that IR is promoted by elevations in hepatic sphingolipids (SL), particularly ceramides, and that Bacteroidetes are the only microbiome phylum possessing genes encoding serine palmitoyltransferase (SPT), which mediates SL synthesis, we investigated a potential link between bacterial SL production, host SL metabolism, and IR. In vitro, bacterial SLs entered colonocytes and were metabolized into complex SL, including ceramides. In mice, administration of WT Bacteroides thetaiotaomicron, but not a SPT-deficient mutant, resulted in elevated levels of liver ceramides and reduced responsiveness to exogenously administered insulin. This work establishes bacterial SLs as a new class of microbiome-derived molecule capable of impacting host metabolism.\n\nOne Sentence SummarySL production by gut Bacteroidetes regulates liver ceramide levels and insulin sensitivity.

microbiology↗

Microbiota-independent antiviral protection conferred by aminoglycoside antibiotics

Antibiotics are widely used to treat infections in humans. However, the impact of antibiotic use on host cells is understudied. We have identified a novel antiviral effect of commonly used aminoglycoside antibiotics. We show that mucosal application of aminoglycosides increased host resistance to a broad range of viral infections including herpes simplex viruses, influenza A virus and Zika virus. Aminoglycoside treatment also reduced viral replication in primary human cells. This antiviral activity was independent of the microbiota as aminoglycoside treatment protected germ-free mice. Microarray analysis uncovered a marked upregulation of transcripts for interferon-stimulated genes (ISGs) following aminoglycoside application. ISG induction was mediated by TLR3, and required TIR-domain-containing adapter-inducing interferon-{beta} (TRIF), signaling adaptor, and interferon regulatory factors 3 (IRF3) and IRF7, transcription factors that promote ISG expression. XCR1+ dendritic cells, which uniquely express TLR3, were recruited to the vaginal mucosa upon aminoglycoside treatment and were required for ISG induction. These results highlight an unexpected ability of aminoglycoside antibiotics to confer broad antiviral resistance in vivo.

immunology↗

Bioinformatics Core Competencies for Undergraduate Life Sciences Education

Bioinformatics is becoming increasingly central to research in the life sciences. However, despite its importance, bioinformatics skills and knowledge are not well integrated in undergraduate biology education. This curricular gap prevents biology students from harnessing the full potential of their education, limiting their career opportunities and slowing genomic research innovation. To advance the integration of bioinformatics into life sciences education, a framework of core bioinformatics competencies is needed. To that end, we here report the results of a survey of life sciences faculty in the United States about teaching bioinformatics to undergraduate life scientists. Responses were received from 1,260 faculty representing institutions in all fifty states with a combined capacity to educate hundreds of thousands of students every year. Results indicate strong, widespread agreement that bioinformatics knowledge and skills are critical for undergraduate life scientists, as well as considerable agreement about which skills are necessary. Perceptions of the importance of some skills varied with the respondents degree of training, time since degree earned, and/or the Carnegie classification of the respondents institution. To assess which skills are currently being taught, we analyzed syllabi of courses with bioinformatics content submitted by survey respondents. Finally, we used the survey results, the analysis of syllabi, and our collective research and teaching expertise to develop a set of bioinformatics core competencies for undergraduate life sciences students. These core competencies are intended to serve as a guide for institutions as they work to integrate bioinformatics into their life sciences curricula.\n\nSignificance StatementBioinformatics, an interdisciplinary field that uses techniques from computer science and mathematics to store, manage, and analyze biological data, is becoming increasingly central to modern biology research. Given the widespread use of bioinformatics and its impacts on societal problem-solving (e.g., in healthcare, agriculture, and natural resources management), there is a growing need for the integration of bioinformatics competencies into undergraduate life sciences education. Here, we present a set of bioinformatics core competencies for undergraduate life scientists developed using the results of a large national survey and the expertise of our working group of bioinformaticians and educators. We also present results from the survey on the importance of bioinformatics skills and the current state of integration of bioinformatics into biology education.

bioinformatics↗