Andrew Goodman

Andrew Goodman
Yale University | YU · Department of Microbial Pathogenesis

About

105
Publications
17,545
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13,939
Citations
Citations since 2016
70 Research Items
10405 Citations
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Introduction

Publications

Publications (105)
Preprint
Full-text available
Dietary nutrients, host metabolism, and gut microbiota activity each influence the host's metabolic phenotype; however, the interplay between these factors remains poorly understood. We employed tissue-resolved metabolomics in gnotobiotic mice carrying a synthetic human gut microbiota and germfree mice in two dietary conditions to develop an intest...
Article
Full-text available
Human gut microbes exhibit a spectrum of cooperative and antagonistic interactions with their host and also with other microbes. The major Bacteroides host-targeting virulence factor, Bacteroides fragilis toxin (BFT), is produced as an inactive protoxin by enterotoxigenic B. fragilis strains. BFT is processed by the conserved bacterial cysteine pro...
Article
Full-text available
The intestinal microbiome and bacterial translocation (BT), the passage of microorganisms from the gut lumen to mesenteric lymph nodes and other extra‐intestinal sites, are main mechanisms implicated in liver injury and further decompensation in patients with cirrhosis. We hypothesized that obeticholic acid (OCA), a semisynthetic bile acid, would c...
Article
Full-text available
The bacteria occupying the mammalian gut have evolved unique strategies to thrive in their environment. Bacteroides organisms, which often comprise 25 to 50% of the human gut microbiota, derive nutrients from structurally diverse complex polysaccharides, commonly called dietary fibers. This ability requires an expansive genetic repertoire that is c...
Article
Bacteroides are one of the most prominent genera in the human gut microbiome, and study of this bacterial group provides insight into gut microbial ecology and pathogenesis. In this report, we introduce a negative selection system for rapid and efficient allelic exchange in wild Bacteroides that does not require any alterations to the genetic backg...
Article
Full-text available
Increasing evidence suggests a role of the gut microbiota in patients’ response to medicinal drugs. In our recent study, we combined genomics of human gut commensals and gnotobiotic animal experiments to quantify microbiota and host contributions to drug metabolism. Informed by experimental data, we built a physiology-based pharmacokinetic model of...
Article
Full-text available
Individuals vary widely in drug responses, which can be dangerous and expensive due to treatment delays and adverse effects. Growing evidence implicates the gut microbiome in this variability, however the molecular mechanisms remain largely unknown. Here we measured the ability of 76 diverse human gut bacteria to metabolize 271 oral drugs and found...
Article
Given the immense antigenic load present in the microbiome, we hypothesized that microbiota mimotopes can be a persistent trigger in human autoimmunity via cross-reactivity. Using antiphospholipid syndrome (APS) as a model, we demonstrate cross-reactivity between non-orthologous mimotopes expressed by a common human gut commensal, Roseburia intesti...
Article
Off-target drug metabolism Anything humans swallow is exposed to the foraging and transforming activities of the gut microbiota. This applies to therapeutic drugs as well as food components and can be a major source of interpersonal variation in drug efficacy and toxicity. Zimmermann et al. found that individual drug responses depend on the genetic...
Article
Significance Diet is known to alter the gut microbiota composition by supplying nutrients that promote the expansion of particular microorganisms. However, we demonstrate that fructose, a common dietary additive in the Western world, decreases the abundance of a regulator of gut colonization in the human gut commensal Bacteroides thetaiotaomicron ....
Article
Full-text available
ELife digest Eating is the first step in an hours-long process that extracts the nutrients we need to live. It not only nourishes us, but also a vast community of bacteria in our gut called the microbiota. The gut microbiota acts like an extension of our immune system and helps us stay healthy in many ways. For example, it blocks pathogens from mak...
Data
(Table S1) Identified BtuB-BtuG pairs from BlastP and Phyre2 searches of BT1490, BT1954 and BT2095. (Table S2) Amino acid sequences of 114 BtuG homologs used to create the sequence logo in Figure 2A. (Table S3) Bacterial strains, plasmids and oligonucleotide primers used in this study.
Article
In the mammalian gut, bacteria compete for resources to maintain their populations, but the factors determining their success are poorly understood. We report that the human gut bacterium Bacteroides thetaiotaomicron relies on the stringent response, an intracellular signaling pathway that allocates resources away from growth, to survive carbon sta...
Article
Full-text available
Antibiotics are widely used to treat infections in humans. However, the impact of antibiotic use on host cells is understudied. Here we identify an antiviral effect of commonly used aminoglycoside antibiotics. We show that topical mucosal application of aminoglycosides prophylactically increased host resistance to a broad range of viral infections...
Article
Full-text available
The earliest autoantibodies in lupus are directed against the RNA binding autoantigen Ro60, but the triggers against this evolutionarily conserved antigen remain elusive. We identified Ro60 orthologs in a subset of human skin, oral, and gut commensal bacterial species and confirmed the presence of these orthologs in patients with lupus and healthy...
Article
Bacterial involvement in autoimmunity The composition of the commensal microbiota is known to influence autoimmune disease development and persistence. Manfredo Vieira et al. identified a gut microbe, Enterococcus gallinarum , that translocates from the gut into the organs of mice with a genetic predisposition to lupus-like autoimmunity (see the Pe...
Article
Coxiella burnetii is an intracellular pathogen that replicates in a lysosome-derived vacuole. A determinant necessary forC. burnetiivirulence is the Dot/Icm type IVB secretion system (T4SS). The Dot/Icm system delivers more than 100 proteins, called type IV effectors (T4Es), across the vacuolar membrane into the host cell cytosol. Several T4Es have...
Preprint
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 s...
Article
Significance The contribution of individual effectors to Legionella pneumophila virulence has not been systematically examined. This study employed a parallel high-throughput transposon insertion sequencing technique called INSeq to probe the L. pneumophila effector repertoire and identified multiple effectors that contribute to virulence in severa...
Article
Full-text available
The microbiome affects development and activity of the immune system, and may modulate immune therapies, but there is little direct information about this control in vivo. We studied how the microbiome affects regulation of human immune cells in humanized mice. When humanized mice were treated with a cocktail of 4 antibiotics, there was an increase...
Article
Although gut microbiome composition is well defined, the mechanisms underlying community assembly remain poorly understood. Bacteroidales possess three genetic architectures (GA1–3) of the type VI secretion system (T6SS), an effector delivery pathway that mediates interbacterial competition. Here we define the distribution and role of GA1–3 in the...
Article
The microbiota contributes to colonization resistance against invading pathogens by competing for metabolites, producing inhibitory substances, and priming protective immune responses. However, the specific commensal bacteria that promote host resistance and immune-mediated protection remain largely elusive. Using isogenic mouse lines with distinct...
Article
Full-text available
Campylobacter jejuni is one of the leading infectious causes of food-borne illness around the world. Its ability to persistently colonize the intestinal tract of a broad range of hosts, including food-producing animals, is central to its epidemiology since most infections are due to the consumption of contaminated food products. Using a highly satu...
Data
Amino acid utilization by C. jejuni 81–176 determined by exometabolome analysis. The uptake of amino acids by C. jejuni 81–176 was examined by measuring their concentrations in the culture supernatants within 24 h of cultivation relative to their original concentration prior to bacterial inoculation, which was considered to be 100%. Shown are the m...
Data
In vivo fitness of C. jejuni insertion mutants determined by INSeq analysis. Relative abundance of C. jejuni insertion mutants in the inoculum and the mouse cecum samples after infection for 4 (A), 7 (B) and 21 (C) days. In (A) and (B), each point represents the average abundance of read numbers of a single gene obtained from 13 or 5 mice, respecti...
Data
Role of amino acid biosynthesis of C. jejuni 81–176 in mouse colonization. Illustrated is the impact of amino acid biosynthesis pathways in C. jejuni mouse intestinal colonization as determined by INSeq analysis. Numbers indicate the log2 value of fold change (intestine/inoculum) in the number of insertions in the indicated genes and are derived fr...
Data
Role of methionine and S-adenosyl methionine (SAM) biosynthesis in C. jejuni 81–176 in vivo growth. Illustrated is the impact of methionine and SAM biosynthesis in C. jejuni mouse intestinal colonization as determined by INSeq analysis. Numbers indicate the log2 value of fold change (intestine/inoculum) in the number of insertions in the indicated...
Data
Impact of the non-oxidative pentose phosphate pathway (PPP) on the growth of C. jejuni 81–176. Shown is the impact of the inactivation of genes encoding components of the PPP pathway in C. jejuni mouse intestinal colonization as determined by INSeq analyses. Numbers indicate the log2 value of fold change (intestine/inoculum) in the number of insert...
Data
Core metabolic reactions of C. jejuni 81–176 that generate carbon dioxide. Selected metabolic reactions in C. jejuni that release carbon dioxide (CO2). Numbers indicate the log2 value of fold change (intestine/inoculum) in the number of insertions in the indicated genes and are derived from the raw data in S3 Table. Values below -6.2 indicate mutat...
Data
INSeq raw data for each gene in mouse colonization experiments, which were normalized by median nomarlization method. (XLSX)
Data
Summary of potassium channel and transporters in Epsilon-proteobacteria. (XLSX)
Data
Contribution of a C. jejuni motility-associated gene cluster to mouse colonization. (A)Blue and red bars indicate the normalized read number of each insertion site within the different ORFs in the input and output pool, respectively. Motility assays (B) and growth curves (see S12 Table) (C) for wild-type C. jejuni 81–176 and the ΔCJJ81176_0479, ΔCJ...
Data
Impact of the purine and pyrimidine biosynthesis pathways on the in vivo growth of C. jejuni 81–176. Shown is the impact of the inactivation of genes encoding components of the purine and pyrimidine biosynthesis pathways in C. jejuni mouse intestinal colonization as determined by INSeq analyses. Numbers indicate the log2 value of fold change (intes...
Data
Analysis of potential polar effects of transposon insertions. (XLSX)
Data
Strains and plasmids used in this study. (XLSX)
Data
Raw data for Figs 6E, 7E, S2B, S7C and S10. (XLSX)
Data
Growth properties of serine-biosynthesis defective C. jejuni mutants. Wild type C. jejuni 81–176 (WT) and the indicated isogenic mutant strains (serA: D-3-phosphoglycerate dehydrogenase; sdaA: L-serine ammonia-lyase/dehydratase) were grown in defined medium (DAAM) in the presence or absence of serine as indicated. Lactate or glutamate are provided...
Data
13C-incorporation and isotopologue profiles of protein-derived amino acids in C. jejuni 81–176 after incubation with [5-13C1]-Glu in DMEM medium. Black columns on the left y axis represent percentage of 13C-excess (mol %) into the respective protein-derived amino acids. The colored columns on the right y axis depict the percentages of labeled isoto...
Data
Role of the “acetate switch” in mouse colonization. Six mice were inoculated with an equal number of wild-type C. jejuni 81–176 and the ΔackA isogenic mutant strain via oral gavage. Competitive indices (CI) were calculated as the ratio of the CFU of the ΔackA mutant over wild type recovered from the ceca of infected mice (see S14 Table). (TIF)
Data
List of genes that show similar mutant phenotype according to the Venn diagram depicted in Fig 1B and 1C. (XLSX)
Data
Summary of INSeq data for Tlp and chemotaxis proteins in C. jejuni 81–176. (XLSX)
Data
Raw data for Figs 2, 5inset, 6C, 6D, S1, S12 and S13. (XLSX)
Data
Raw data for Figs 7D, S4 and S14. (XLSX)
Data
Labeling of polar metabolites in C. jejuni 81–176 upon cultivation with [3-13C1]Ser. Shown are the 13C-incorporation (13C-excess) and the relative isotopologue distributions into polar metabolites isolated from the cytoplasm of C. jejuni after incubation with [3-13C1]Ser. Illustrated are the means ± SD of 6 measurements with the colored boxes indic...
Data
Amino acid uptake ability of C. jejuni 81–176. (A) Scheme presenting the predicted amino acid uptake capacity of C. jejuni 81–176 according to the INSeq analysis. Viable mutants with transposon insertions in the indicated amino acid biosynthesis pathways have been identified in the screen suggesting the import of respective amino acids. No transpos...
Data
Colony forming units of commensal bacteria in mice feces before and after antibiotic treatment. Shown is the intestinal bacterial load after antibiotic treatment of animals immediately prior to infection with C. jejuni. Collected feces samples from each mouse were dissolved and diluted serially with PBS buffer, then plated on blood agar in duplicat...
Data
Log2 (output/input) ratio distribution of all insertions during mouse colonization. Histogram depicting the number of genes (y axis) that exhibited the indicated log2 [fold change (output/input)] change (x axis) in the numbers of transposon insertions recovered from infected mice relative to the number of transposon insertions in the original inocu...
Data
Amino acid composition of all predicted proteins encoded by C. jejuni 81–176. The frequency of all amino acids in all predicted proteins are shown and branched-chain amino acids are highlighted in orange. Calculations were carried out using BacMap (http://wishart.biology.ualberta.ca/BacMap/cgi/getGraphs.cgi?accession=NC_008787&ref=index_2.html). (T...
Data
Schematic overview of the 13C-flux into protein-derived amino acids after catabolism of [5-13C1]-Glu in C. jejuni 81–176. The positions of the 13C-label of the amino acid isotopologues are indicated by the colored dots. Due to the stereoisomerism of the TCA-cycle intermediates succinate and fumarate, it is not possible to distinguish between the C1...
Data
INSeq raw data for each C. jejuni gene after growth under different in-vitro growth condition. (XLSX)
Data
INSeq raw data for each gene in mouse colonization experiments. (XLSX)
Data
Growth-promoting substrates utilized by Campylobacter jejuni during colonization of gastrointestinal tract. (DOCX)
Data
Composition of a modified defined DMEM medium for Campylobacter jejuni 81–176 used in the indicated studies. (XLSX)
Data
Raw data for S3 Fig. (XLSX)
Data
Supplementary methods. (DOCX)
Preprint
While the composition of the human gut microbiome has been well defined, the forces governing its assembly are poorly understood. Recently, prominent members of this community from the order Bacteroidales were shown to possess the type VI secretion system (T6SS), which mediates contact-dependent antagonism between Gram-negative bacteria. However, t...
Article
Over the last decade, our appreciation for the contribution of resident gut microorganisms—the gut microbiota—to human health has surged. However, progress is limited by the sheer diversity and complexity of these microbial communities. Compounding the challenge, the majority of our commensal microorganisms are not close relatives of Escherichia co...
Article
The gut microbiota is implicated in numerous aspects of health and disease, but dissecting these connections is challenging because genetic tools for gut anaerobes are limited. Inducible promoters are particularly valuable tools because these platforms allow real-time analysis of the contribution of microbiome gene products to community assembly, h...
Conference Paper
Background and aims The antiphospholipid syndrome (APS) is an autoimmune thrombophilic non-gut disorder with high mortality. Various pathogens have been associated with transient antiphospholipid antibody production. We hypothesised that members of the gut microbiota in APS patients could represent a chronic trigger and exhibit heightened adaptive...
Article
Full-text available
Archaea are habitual residents of the human gut flora but are detected at substantially lower frequencies than bacteria. Previous studies have indicated that each human harbors very few archaeal species. However, the low diversity of human-associated archaea that has been detected could be due to the preponderance of bacteria in these communities,...
Article
Obesity, insulin resistance and the metabolic syndrome are associated with changes to the gut microbiota; however, the mechanism by which modifications to the gut microbiota might lead to these conditions is unknown. Here we show that increased production of acetate by an altered gut microbiota in rodents leads to activation of the parasympathetic...
Article
Significance The microbial community in the human gut represents one of the densest known ecosystems. Community composition has broad impacts on health, and metabolic competition and host selection have both been implicated in shaping these communities. Here, we report that contact-dependent bacterial antagonism also determines the ability of human...
Article
Expansion of the genetic code with nonstandard amino acids (nsAAs) has enabled biosynthesis of proteins with diverse new chemistries. However, this technology has been largely restricted to proteins containing a single or few nsAA instances. Here we describe an in vivo evolution approach in a genomically recoded Escherichia coli strain for the sele...
Article
Microbe-induced receptor trafficking has emerged as an essential means to promote innate immune signal transduction. Upon detection of bacterial lipopolysaccharides (LPS), CD14 induces an inflammatory endocytosis pathway that delivers Toll-like receptor 4 (TLR4) to endosomes. Although several regulators of CD14-dependent TLR4 endocytosis have been...