About

Sam Light, PhD, is the Neubauer Family Assistant Professor of Microbiology at the University of Chicago within the Department of Microbiology. His research focuses on bacterial pathogenesis, the human microbiome, microbial genetics, and protein biochemistry. His work aims to develop a fundamental understanding of the relationship between microbial metabolism and the health or diseased states of the gut microbiota, with the goal of exploiting these insights for targeted therapies. Dr. Light's research investigates how microbes exhibit variable cellular metabolic processes that influence microbial ecosystems, particularly in the gut, by generating small molecules that impact host biology. He has a background that includes postdoctoral training at the University of California Berkeley and Northwestern University, where he continued his research in microbiology and metabolism. His scholarly contributions include studies on DNA-utilization loci in gut Bacteroidales, gut bacteria metabolism of natural and synthetic steroid hormones, and the regulation of immune responses to food by commensal microbes. Dr. Light's work also explores bacterial electron transfer mechanisms and the role of microbes in kelp forest ecosystems, emphasizing his broad interest in microbial functions and interactions within various environments.

Research topics

• Biochemistry
• Biology
• Bioinformatics
• Microbiology
• Medicine
• Gastroenterology
• Immunology
• Genetics
• Internal medicine
• Chemistry
• Cell biology

Selected publications

• NyQuil, Shoes without Laces, and a Psychiatric Hospital in Petaluma

  DigitalCommons - CalPoly (California State Polytechnic University) · 2026-02-17

  articleOpen access1st authorCorresponding

  Reflective Memo: LOL, I don't really get what you're supposed to say in this so-called "Reflective Memo" section.I guess I'll tell you the prompt so you can read this with some sort of context.Yes, this seems like a good idea.I shall do it.Okay, prompt: describe one significant moment and reflect on how this moment has shaped you as a writer, student,

  PublisherOA PDF

• The intestinal microbiota impacts nutritional immunity and resistance to <i>Acinetobacter baumannii</i> pneumonia

  Proceedings of the National Academy of Sciences · 2026-04-21

  articleOpen access

  Broad-spectrum antibiotics are frequently administered to intensive care unit patients as part of empiric care. This treatment has been associated with subsequent infections by the emerging nosocomial pathogen Acinetobacter baumannii ; however, the mechanisms underlying this linkage remain unclear. Here, we observe an association between antibiotic treatment and microbiota disruption that precedes A. baumannii infection in a hospitalized patient cohort and demonstrate in a murine model that broad-spectrum antibiotic administration drives susceptibility to intranasal infection with this pathogen. Reconstitution of the intestinal microbiota by fecal microbiota transplant restores control of A. baumannii bloodstream dissemination, implicating microbiota dysbiosis as a key driver of pulmonary disease. Using single-cell RNA sequencing, we determine that antibiotic pretreatment reduces the abundance of transcripts related to phagocyte effector functions in the lung, including nutritional immunity pathways that restrict pathogen access to essential nutrient metals. Depletion studies identify neutrophils and inflammatory monocytes as central mediators of microbiota-dependent protection, and loss of the nutritional immunity components lipocalin-2 or calprotectin abrogates the effects of antibiotics on infected mice, demonstrating a causal relationship between microbiota dysbiosis and impaired phagocyte-mediated nutritional immunity. Together, these findings provide a mechanism for the increased severity of A. baumannii pneumonia following antibiotic exposure and highlight the intestinal microbiota as a potential therapeutic target to prevent nosocomial infections with this and other healthcare-associated pathogens.

  PublisherOA PDFDOI

• DNA-utilization loci enable exogenous DNA metabolism in gut Bacteroidales

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-18 · 1 citations

  preprintOpen accessSenior authorCorresponding

  ABSTRACT The human gut microbiome plays a central role in nutrient metabolism, yet the fate of exogenous nucleic acids within this ecosystem remains poorly understood. Here, we show that multiple Bacteroidales species efficiently metabolize exogenous DNA, with Bacteroides thetaiotaomicron converting it into the deaminated nucleobases uracil and xanthine. Using genetic and biochemical approaches, we identify ddbABCDEF , a six-gene locus encoding secreted nucleases and an outer membrane transporter, essential for exogenous DNA metabolism in B. thetaiotaomicron . Colonization of gnotobiotic mice with ddbABCDEF mutants reveals that this pathway significantly alters nucleobase pools in the gut. Comparative genomics demonstrate that ddbABCDEF is evolutionarily related to a natural transformation system present in Bacteroidota and has diversified into four distinct subtypes, each linked to unique DNA-processing activities in closely related gut Bacteroidales strains. These findings thus establish DNA as a metabolic substrate in the gut microbiome and reveal a distinctive pathway for nucleobase production with implications for host-microbe interactions. SIGNIFICANCE STATEMENT The gut microbiome plays a crucial role in nutrient metabolism, yet the fate of extracellular DNA within this ecosystem remains poorly understood. This study identifies Bacteroidales species that actively metabolize extracellular DNA, revealing a conserved pathway that converts DNA-derived nucleotides into deaminated nucleobases. We show that Bacteroides thetaiotaomicron utilizes a specialized genetic locus, ddbABCDEF , to facilitate this process, influencing nucleobase availability in the gut. Comparative genomic analyses suggest that ddbABCDEF is evolutionarily linked to bacterial natural transformation systems but has diverged into distinct metabolic subtypes. These findings establish DNA as a metabolic substrate in the gut microbiome, with potential implications for microbial ecology, host-microbe interactions, and gut health.

  PublisherOA PDFDOI

• Quantitative insights into the efficacy of genome-resolved surveys of microbial communities through ribosomal protein phylogeography and EcoPhylo

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-15 · 3 citations

  preprintOpen access

  The increasing availability of microbial genomes is essential to gain insights into microbial ecology and evolution that can propel biotechnological and biomedical advances. Recent advances in genome recovery have significantly expanded the catalogue of microbial genomes from diverse habitats. However, the ability to explain how well a set of genomes account for the diversity in a given environment remains challenging for individual studies or biome-specific databases. Here we present EcoPhylo, a computational workflow to characterize the phylogeography of any gene family through integrated analyses of genomes and metagenomes, and apply this approach to ribosomal proteins to quantify phylogeny-aware genome recovery rates in two genome-resolved investigations of the human gut and oral cavity. Our results demonstrate that EcoPhylo reveals highly resolved, reference-free, multi-domain phylogenies in conjunction with distribution patterns of individual clades across environments, providing a means to assess genome recovery in individual studies and benchmark genome collections.

  PublisherDOI

• DNA-utilization loci enable exogenous DNA metabolism in gut Bacteroidales

  Proceedings of the National Academy of Sciences · 2025-09-16

  articleOpen accessSenior authorCorresponding

  The human gut microbiome plays a central role in nutrient metabolism, yet the fate of exogenous nucleic acids within this ecosystem remains poorly understood. Here, we show that multiple Bacteroidales species efficiently metabolize exogenous DNA, with Bacteroides thetaiotaomicron converting it into the deaminated nucleobases uracil and xanthine. Using genetic and biochemical approaches, we identify ddbABCDEF , a six-gene locus encoding secreted nucleases and an outer membrane transporter, essential for exogenous DNA metabolism in B. thetaiotaomicron . Colonization of gnotobiotic mice with ddbABCDEF mutants reveals that this pathway significantly alters nucleobase pools in a gnotobiotic mouse model. Comparative genomic analyses demonstrate that ddbABCDEF is evolutionarily related to a natural transformation system present in Bacteroidota and has diversified into four distinct subtypes, each linked to unique DNA-processing activities in closely related gut Bacteroidales strains. These findings thus expand our understanding of DNA metabolism in the gut microbiome and reveal a distinctive pathway for nucleobase production with implications for host–microbe interactions.

  PublisherDOI

• Gut bacteria metabolize natural and synthetic steroid hormones via the reductive OsrABC pathway

  Cell Host & Microbe · 2025-10-21 · 9 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Author Correction: Dietary- and host-derived metabolites are used by diverse gut bacteria for anaerobic respiration

  Nature Microbiology · 2025-05-16

  erratumOpen accessSenior author
  PublisherOA PDFDOI

• Dietary- and host-derived metabolites are used by diverse gut bacteria for anaerobic respiration

  Nature Microbiology · 2024 · 70 citations

  Senior authorCorresponding
  • Biology
  • Biochemistry
  • Microbiology
  PublisherOA PDFDOI

• Versatile roles of protein flavinylation in bacterial extracyotosolic electron transfer

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-03-14 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Bacteria perform diverse redox chemistries in the periplasm, cell wall, and extracellular space. Electron transfer for these extracytosolic activities is frequently mediated by proteins with covalently bound flavins, which are attached through post-translational flavinylation by the enzyme ApbE. Despite the significance of protein flavinylation to bacterial physiology, the basis and function of this modification remains unresolved. Here we apply genomic context analyses, computational structural biology, and biochemical studies to address the role of ApbE flavinylation throughout bacterial life. We find that ApbE flavinylation sites exhibit substantial structural heterogeneity. We identify two novel classes of flavinylation substrates that are related to characterized proteins with non-covalently bound flavins, providing evidence that protein flavinylation can evolve from a non-covalent flavoprotein precursor. We further find a group of structurally related flavinylation-associated cytochromes, including those with the domain of unknown function DUF4405, that presumably mediate electron transfer in the cytoplasmic membrane. DUF4405 homologs are widespread in bacteria and related to ferrosome iron storage organelle proteins that may facilitate iron redox cycling within ferrosomes. These studies reveal a complex basis for flavinylated electron transfer and highlight the discovery power of coupling comparative genomic analyses with high-quality structural models.

  PublisherOA PDFDOI

• Bacteria on the foundational kelp in kelp forest ecosystems: Insights from culturing, whole genome sequencing and metabolic assays

  Environmental Microbiology Reports · 2024-05-22 · 11 citations

  articleOpen access

  In coastal marine ecosystems, kelp forests serve as a vital habitat for numerous species and significantly influence local nutrient cycles. Bull kelp, or Nereocystis luetkeana, is a foundational species in the iconic kelp forests of the northeast Pacific Ocean and harbours a complex microbial community with potential implications for kelp health. Here, we report the isolation and functional characterisation of 16 Nereocystis-associated bacterial species, comprising 13 Gammaproteobacteria, 2 Flavobacteriia and 1 Actinomycetia. Genome analyses of these isolates highlight metabolisms potentially beneficial to the host, such as B vitamin synthesis and nitrogen retention. Assays revealed that kelp-associated bacteria thrive on amino acids found in high concentrations in the ocean and in the kelp (glutamine and asparagine), generating ammonium that may facilitate host nitrogen acquisition. Multiple isolates have genes indicative of interactions with key elemental cycles in the ocean, including carbon, nitrogen and sulphur. We thus report a collection of kelp-associated microbial isolates that provide functional insight for the future study of kelp-microbe interactions.

  PublisherOA PDFDOI

Recent grants

• Electrogenic metabolism in host-associated microbial communities andpathogenesis

  NIH · $268k · 2020–2023

• Characterizing the role of an extracellular electron transport chain in Listeria monocytogenes virulence factor expression and metabolism

  NIH · $131k · 2018–2020

Frequent coauthors

• Raphaël Méheust

  43 shared

• W.F. Anderson

  Northwestern University

  28 shared

• G. Minasov

  Northwestern University

  18 shared

• L. Shuvalova

  Northwestern University

  10 shared

• Arnon Lavie

  University of Illinois Chicago

  10 shared

• Jillian F. Banfield

  University of California, Berkeley

  10 shared

• Rafael Rivera‐Lugo

  University of California, Berkeley

  9 shared

• Caroline M. Ajo‐Franklin

  9 shared

Education

• Ph.D.

  Northwestern University

  2013

• B.A.

  Bard College

  2008