Identifying genetic determinants needed to establish a human gut symbiont in its habitat

By A. Goodman, N. McNulty, Yue Zhao, Douglas D. Leip, Robi David Mitra, Catherine A. Lozupone, Rob Knight, Jeffrey I. Gordon. Cell Host and Microbe, 2009

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Summary The human gut microbiota is a metabolic organ whose cellular composition is determined by a dynamic process of selection and competition. To identify microbial genes required for establishment of human symbionts in the gut, we developed an approach (insertion-sequencing, or INSeq) based on a mutagenic transposon that allows capture of adjacent chromosomal DNA to define its genomic location. We used massively parallel sequencing to monitor the relative abundance of tens of thousands of transposon mutants of a saccharolytic human gut bacterium, Bacteroides thetaiotaomicron, as they established themselves in wild-type and immunodeficient gnotobiotic mice, in the presence or absence of other human gut commensals. In vivo selection transforms this population, revealing functions necessary for survival in the gut: we show how this selection is influenced by community composition and competition for nutrients (vitamin B12). INSeq provides a broadly applicable platform to explore microbial adaptation to the gut and other ecosystems.

Subfields: Infectious Diseases, Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/f183e31ce026cff6e3c2d14ec55e4e094b606eea

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Citations in the corpus

Phenotypic Landscape of a Bacterial Cell (2010, neutral): “To make this approach a reality, low-cost methods for developing deletion libraries must be developed (Goodman et al., 2009).”
DEG 10, an update of the database of essential genes that includes both protein-coding genes and noncoding genomic elements (2013, methodology): “One illustrative example is the study on genes required to establish a human gut symbiont (14).”
Defining the Human Microbiome (2012, background): “Emerging technologies such as stool transplantation, 16S rRNA and whole-genome sequencing on the Illumina platform, the ability to transplant human microbial communities into mice with high efficiency even from frozen samples[50], and the creation of personalized culture collections[74] raises the p”
High-Resolution Phenotypic Profiling Defines Genes Essential for Mycobacterial Growth and Cholesterol Catabolism (2011, methodology): “others have used similar deep sequencing methods to map insertion sites in other organisms [28,29,30,31,32] our new analytical tools allowed the statistically rigorous prediction of the”
How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans (2017, background): “(29) identified through transposon mutagenesis genes in Bt important for colonization of the mouse gut.”
Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice (2011, methodology): “A single vial of the −80 °C anaerobic glycerol stock containing an aliquot of a fecal sample from Donor 2 was diluted into prereduced TYGs medium lacking resazurin (1) in an anaerobic chamber and was dispensed into prereduced 384-well flat-bottomed trays (170 μL per well).”