- April 14, 2025Source: Yale News
Infection Control: How a Pathogen Survives a Hostile Environment
- March 17, 2023Source: Yale News
Boosting Survival of a Beneficial Bacterium in the Human Gut
- January 09, 2023
Postdoctoral position available in the Groisman lab, Microbial Sciences Institute at Yale University
- August 10, 2022
Dr. Weiwei Han presents Ph.D. thesis
Welcome
The Groisman Lab seeks to discover new biological principles by investigating how beneficial and pathogenic bacteria interact with their mammalian hosts.
We aim to reveal the mechanisms that promote the fitness of beneficial gut bacteria and those that confer virulence and resistance to antimicrobial agents on pathogens.
Research Focus
Science 2023 Bacteria require phase separation for fitness in the mammalian gut
RNA-seq analysis was performed in cecal contents of ex-germ-free mice (C57BL/6 mice, n = 5) monocolonized with strains harboring WT Rho (AK310) or ?IDR (AK312) Rho. (A) Volcano plot of gene RNA abundance in the WT versus ?IDR Rho strains as log2-fold change versus -log(p). Genes >2-fold up-regulated (blue) or down-regulated (orange) in the ?IDR background are highlighted. (FDR-adjusted P value <0.05). (B) Heat map of genes differentially expressed in strains harboring WT Rho versus ?IDR Rho based on molecular function. (C) KEGG pathway enrichment analysis of differentially expressed in strains harboring WT Rho versus ?IDR Rho. Identified pathways with enrichment p-value <0.05 and number of genes per pathway shown. (D) Log2 fold change of genes identified in (C).
Han EMBO 2023 Gut colonization by Bacteroides requires translation by an EF-G paralog lacking GTPase activity.
Gut-commensal Bacteroides thetaiotaomicron harbors a second paralog of translation elongation factor EF-G, EF-G2. Here, EF-G2 is found to increase bacterial fitness in the nutrient-fluctuating gut environment by mediating slow translation without GTP hydrolysis.
Choi PNAS 2022 H-NS degradation is necessary for gut colonization by E. coli.
Salvail PLOS Gen 2022 Differential synthesis of novel small protein times Salmonella virulence program.
Two different mRNAs from the ugtSugtL bicistron time the S. Typhimurium PhoP virulence program inside macrophages.
Pontes Sci Signal Cover We report that persistent bacteria form as a result of slow growth alone, despite opposite changes in the abundance of proteins, metabolites, and signaling molecules. Our findings argue that transitory disturbances to core activities, which are often linked to cell growth, promote a persister state regardless of the underlying physiological process responsible for the change in growth.Choi JB Cover The bacterium Salmonella enterica serovar Typhimurium narrows down the spectrum of substrates degraded by the proteases Lon and ClpAP in response to low cytoplasmic Mg2+, a condition that decreases protein synthesis. This control is exerted by PhoP, a transcriptional regulator activated in low cytoplasmic Mg2+ that governs proteostasis and is conserved in enteric bacteria. The uncovered mechanism enables bacteria to control the abundance of preexisting proteins.Gao PNAS The Expanded Specificity and Physiological Role of a Widespread N-degron Recognin.
Candidate ClpS substrates revealed by proteomics.
Yeom PNAS The small proteins MgtU and MgtR regulate Salmonella virulence and growth in low Mg2+ conditions by controlling the stability of the Mg2+ transporters MgtA and MgtB.
Duprey mBio FEDS: a Novel Fluorescence-Based High-Throughput Method for Measuring DNA Supercoiling In Vivo.
Map of SupR, a supercoiling reporter plasmid for enterobacteria.
Townsend PNAS (JA gut image) Dietary sugar silences a colonization factor in a mammalian gut symbiont.
Dietary components are believed to influence the composition of the gut microbiota by serving as nutrients to a subset of microbes, thereby favoring their expansion. However, we now report that dietary fructose and glucose, which are prevalent in the Western diet, specifically silence a protein that is necessary for gut colonization, but not for utilization of these sugars, by the human gut commensal Bacteroides thetaiotaomicron. Our findings underscore a role for dietary sugars that escape absorption by the host intestine and reach the microbiota: regulation of gut colonization by beneficial microbes independently of supplying nutrients to the microbiota.
Schwalm Trends Microbiol Review Metabolic flux controls chondroitin sulfate utilization in Bacteroides thetaiotaomicron.JB Cover 2021 Science 2023 Bacteria require phase separation for fitness in the mammalian gut
RNA-seq analysis was performed in cecal contents of ex-germ-free mice (C57BL/6 mice, n = 5) monocolonized with strains harboring WT Rho (AK310) or ?IDR (AK312) Rho. (A) Volcano plot of gene RNA abundance in the WT versus ?IDR Rho strains as log2-fold change versus -log(p). Genes >2-fold up-regulated (blue) or down-regulated (orange) in the ?IDR background are highlighted. (FDR-adjusted P value <0.05). (B) Heat map of genes differentially expressed in strains harboring WT Rho versus ?IDR Rho based on molecular function. (C) KEGG pathway enrichment analysis of differentially expressed in strains harboring WT Rho versus ?IDR Rho. Identified pathways with enrichment p-value <0.05 and number of genes per pathway shown. (D) Log2 fold change of genes identified in (C).
Han EMBO 2023 Gut colonization by Bacteroides requires translation by an EF-G paralog lacking GTPase activity.
Gut-commensal Bacteroides thetaiotaomicron harbors a second paralog of translation elongation factor EF-G, EF-G2. Here, EF-G2 is found to increase bacterial fitness in the nutrient-fluctuating gut environment by mediating slow translation without GTP hydrolysis.
Choi PNAS 2022 H-NS degradation is necessary for gut colonization by E. coli.
Salvail PLOS Gen 2022 Differential synthesis of novel small protein times Salmonella virulence program.
Two different mRNAs from the ugtSugtL bicistron time the S. Typhimurium PhoP virulence program inside macrophages.
Pontes Sci Signal Cover We report that persistent bacteria form as a result of slow growth alone, despite opposite changes in the abundance of proteins, metabolites, and signaling molecules. Our findings argue that transitory disturbances to core activities, which are often linked to cell growth, promote a persister state regardless of the underlying physiological process responsible for the change in growth.Choi JB Cover The bacterium Salmonella enterica serovar Typhimurium narrows down the spectrum of substrates degraded by the proteases Lon and ClpAP in response to low cytoplasmic Mg2+, a condition that decreases protein synthesis. This control is exerted by PhoP, a transcriptional regulator activated in low cytoplasmic Mg2+ that governs proteostasis and is conserved in enteric bacteria. The uncovered mechanism enables bacteria to control the abundance of preexisting proteins.Gao PNAS The Expanded Specificity and Physiological Role of a Widespread N-degron Recognin.
Candidate ClpS substrates revealed by proteomics.
Yeom PNAS The small proteins MgtU and MgtR regulate Salmonella virulence and growth in low Mg2+ conditions by controlling the stability of the Mg2+ transporters MgtA and MgtB.
Duprey mBio FEDS: a Novel Fluorescence-Based High-Throughput Method for Measuring DNA Supercoiling In Vivo.
Map of SupR, a supercoiling reporter plasmid for enterobacteria.
Townsend PNAS (JA gut image) Dietary sugar silences a colonization factor in a mammalian gut symbiont.
Dietary components are believed to influence the composition of the gut microbiota by serving as nutrients to a subset of microbes, thereby favoring their expansion. However, we now report that dietary fructose and glucose, which are prevalent in the Western diet, specifically silence a protein that is necessary for gut colonization, but not for utilization of these sugars, by the human gut commensal Bacteroides thetaiotaomicron. Our findings underscore a role for dietary sugars that escape absorption by the host intestine and reach the microbiota: regulation of gut colonization by beneficial microbes independently of supplying nutrients to the microbiota.
Schwalm Trends Microbiol Review Metabolic flux controls chondroitin sulfate utilization in Bacteroides thetaiotaomicron.JB Cover 2021 Science 2023 Bacteria require phase separation for fitness in the mammalian gut
RNA-seq analysis was performed in cecal contents of ex-germ-free mice (C57BL/6 mice, n = 5) monocolonized with strains harboring WT Rho (AK310) or ?IDR (AK312) Rho. (A) Volcano plot of gene RNA abundance in the WT versus ?IDR Rho strains as log2-fold change versus -log(p). Genes >2-fold up-regulated (blue) or down-regulated (orange) in the ?IDR background are highlighted. (FDR-adjusted P value <0.05). (B) Heat map of genes differentially expressed in strains harboring WT Rho versus ?IDR Rho based on molecular function. (C) KEGG pathway enrichment analysis of differentially expressed in strains harboring WT Rho versus ?IDR Rho. Identified pathways with enrichment p-value <0.05 and number of genes per pathway shown. (D) Log2 fold change of genes identified in (C).
Han EMBO 2023 Gut colonization by Bacteroides requires translation by an EF-G paralog lacking GTPase activity.
Gut-commensal Bacteroides thetaiotaomicron harbors a second paralog of translation elongation factor EF-G, EF-G2. Here, EF-G2 is found to increase bacterial fitness in the nutrient-fluctuating gut environment by mediating slow translation without GTP hydrolysis.
Choi PNAS 2022 H-NS degradation is necessary for gut colonization by E. coli.
Salvail PLOS Gen 2022 Differential synthesis of novel small protein times Salmonella virulence program.
Two different mRNAs from the ugtSugtL bicistron time the S. Typhimurium PhoP virulence program inside macrophages.
Pontes Sci Signal Cover We report that persistent bacteria form as a result of slow growth alone, despite opposite changes in the abundance of proteins, metabolites, and signaling molecules. Our findings argue that transitory disturbances to core activities, which are often linked to cell growth, promote a persister state regardless of the underlying physiological process responsible for the change in growth.Choi JB Cover The bacterium Salmonella enterica serovar Typhimurium narrows down the spectrum of substrates degraded by the proteases Lon and ClpAP in response to low cytoplasmic Mg2+, a condition that decreases protein synthesis. This control is exerted by PhoP, a transcriptional regulator activated in low cytoplasmic Mg2+ that governs proteostasis and is conserved in enteric bacteria. The uncovered mechanism enables bacteria to control the abundance of preexisting proteins.Gao PNAS The Expanded Specificity and Physiological Role of a Widespread N-degron Recognin.
Candidate ClpS substrates revealed by proteomics.
Yeom PNAS The small proteins MgtU and MgtR regulate Salmonella virulence and growth in low Mg2+ conditions by controlling the stability of the Mg2+ transporters MgtA and MgtB.
Duprey mBio FEDS: a Novel Fluorescence-Based High-Throughput Method for Measuring DNA Supercoiling In Vivo.
Map of SupR, a supercoiling reporter plasmid for enterobacteria.
Townsend PNAS (JA gut image) Dietary sugar silences a colonization factor in a mammalian gut symbiont.
Dietary components are believed to influence the composition of the gut microbiota by serving as nutrients to a subset of microbes, thereby favoring their expansion. However, we now report that dietary fructose and glucose, which are prevalent in the Western diet, specifically silence a protein that is necessary for gut colonization, but not for utilization of these sugars, by the human gut commensal Bacteroides thetaiotaomicron. Our findings underscore a role for dietary sugars that escape absorption by the host intestine and reach the microbiota: regulation of gut colonization by beneficial microbes independently of supplying nutrients to the microbiota.
Schwalm Trends Microbiol Review Metabolic flux controls chondroitin sulfate utilization in Bacteroides thetaiotaomicron.JB Cover 2021
Contact us
Department of Microbial Pathogenesis, Boyer Center for Molecular Medicine, 295 Congress Ave BCMM 341-343, New Haven, CT 06519