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Clare Smith

Assistant Professor of Molecular Genetics and Microbiology
Molecular Genetics and Microbiology
264 Jones, Box 3054, Durham, NC 27710
270 Jones BOX3054, 207 Research Drive, Durham, NC 27710

Selected Publications


The Updated Mouse Universal Genotyping Array Bioinformatic Pipeline Improves Genetic QC in Laboratory Mice.

Journal Article bioRxiv · March 3, 2024 The MiniMUGA genotyping array is a popular tool for genetic QC of laboratory mice and genotyping of samples from most types of experimental crosses involving laboratory strains, particularly for reduced complexity crosses. The content of the production ver ... Full text Link to item Cite

Glycerol contributes to tuberculosis susceptibility in male mice with type 2 diabetes.

Journal Article Nat Commun · September 20, 2023 Diabetes mellitus increases risk for tuberculosis disease and adverse outcomes. Most people with both conditions have type 2 diabetes, but it is unknown if type 1 and type 2 diabetes have identical effects on tuberculosis susceptibility. Here we show that ... Full text Link to item Cite

Genome-wide screen identifies host loci that modulate Mycobacterium tuberculosis fitness in immunodivergent mice.

Journal Article G3 (Bethesda) · August 30, 2023 Featured Publication Genetic differences among mammalian hosts and among strains of Mycobacterium tuberculosis (Mtb) are well-established determinants of tuberculosis (TB) patient outcomes. The advent of recombinant inbred mouse panels and next-generation transposon mutagenesi ... Full text Link to item Cite

Mycobacterial Genetic Technologies for Probing the Host-Pathogen Microenvironment.

Journal Article Infect Immun · June 15, 2023 Featured Publication Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is one of the oldest and most successful pathogens in the world. Diverse selective pressures encountered within host cells have directed the evolution of unique phenotypic traits, resul ... Full text Link to item Cite

Differential Requirement for IRGM Proteins during Tuberculosis Infection in Mice.

Journal Article Infect Immun · February 16, 2023 Featured Publication Mycobacterium tuberculosis (Mtb) is a bacterium that exclusively resides in human hosts and remains a dominant cause of morbidity and mortality among infectious diseases worldwide. Host protection against Mtb infection is dependent on the function of immun ... Full text Link to item Cite

Mycobacterium tuberculosis Evasion of Guanylate Binding Protein-Mediated Host Defense in Mice Requires the ESX1 Secretion System.

Journal Article Int J Mol Sci · February 2, 2023 Cell-intrinsic immune mechanisms control intracellular pathogens that infect eukaryotes. The intracellular pathogen Mycobacterium tuberculosis (Mtb) evolved to withstand cell-autonomous immunity to cause persistent infections and disease. A potent inducer ... Full text Link to item Cite

An ancestral mycobacterial effector promotes dissemination of infection.

Journal Article Cell · November 23, 2022 Featured Publication The human pathogen Mycobacterium tuberculosis typically causes lung disease but can also disseminate to other tissues. We identified a M. tuberculosis (Mtb) outbreak presenting with unusually high rates of extrapulmonary dissemination and bone disease. We ... Full text Link to item Cite

Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication.

Journal Article Sci Signal · October 25, 2022 Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccin ... Full text Open Access Link to item Cite

Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice.

Journal Article Elife · February 3, 2022 Featured Publication The outcome of an encounter with Mycobacterium tuberculosis (Mtb) depends on the pathogen's ability to adapt to the variable immune pressures exerted by the host. Understanding this interplay has proven difficult, largely because experimentally tractable a ... Full text Link to item Cite

TMEM41B is a host factor required for the replication of diverse coronaviruses including SARS-CoV-2.

Journal Article PLoS Pathog · May 2021 Featured Publication Antiviral therapeutics are a front-line defense against virally induced diseases. Because viruses frequently mutate to escape direct inhibition of viral proteins, there is interest in targeting the host proteins that the virus must co-opt to complete its r ... Full text Link to item Cite

These Are the Genes You're Looking For: Finding Host Resistance Genes.

Journal Article Trends Microbiol · April 2021 Featured Publication Humanity's ongoing struggle with new, re-emerging and endemic infectious diseases serves as a frequent reminder of the need to understand host-pathogen interactions. Recent advances in genomics have dramatically advanced our understanding of how genetics c ... Full text Link to item Cite

Granulocytes act as a niche for Mycobacterium tuberculosis growth.

Journal Article Mucosal Immunol · January 2021 Granulocyte recruitment to the pulmonary compartment is a hallmark of progressive tuberculosis (TB). This process is well-documented to promote immunopathology, but can also enhance the replication of the pathogen. Both the specific granulocytes responsibl ... Full text Link to item Cite

The FDA-approved drug Alectinib compromises SARS-CoV-2 nucleocapsid phosphorylation and inhibits viral infection in vitro.

Journal Article bioRxiv · December 16, 2020 While vaccines are vital for preventing COVID-19 infections, it is critical to develop new therapies to treat patients who become infected. Pharmacological targeting of a host factor required for viral replication can suppress viral spread with a low proba ... Full text Link to item Cite

Content and Performance of the MiniMUGA Genotyping Array: A New Tool To Improve Rigor and Reproducibility in Mouse Research.

Journal Article Genetics · December 2020 The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and the ability to precisely manipulate its genome. Despite the importance of genetics for mouse resea ... Full text Link to item Cite

Distinct Bacterial Pathways Influence the Efficacy of Antibiotics against Mycobacterium tuberculosis.

Journal Article mSystems · August 4, 2020 Effective tuberculosis treatment requires at least 6 months of combination therapy. Alterations in the physiological state of the bacterium during infection are thought to reduce drug efficacy and prolong the necessary treatment period, but the nature of t ... Full text Link to item Cite

Mycobacterium tuberculosisevasion of Guanylate Binding Protein-mediated host defense in mice requires the ESX1 secretion system

Journal Article · 2020 Cell-intrinsic immune mechanisms control intracellular pathogens that infect eukaryotes. The intracellular pathogen Mycobacterium tuberculosis ( Mtb ) evolved to withstand cell-autonomous immunity to cause persistent infections and disease. A potent induce ... Full text Cite

Host-pathogen genetic interactions underlie tuberculosis susceptibility

Journal Article · 2020 The outcome of an encounter with Mycobacterium tuberculosis depends on the pathogen’s ability to adapt to the variable immune pressures exerted by the host. Understanding this interplay has proven difficult, largely because experimentally tractable animal ... Full text Cite

The Updated Mouse Universal Genotyping Array Bioinformatic Pipeline Improves Genetic QC in Laboratory Mice.

Journal Article bioRxiv · March 3, 2024 The MiniMUGA genotyping array is a popular tool for genetic QC of laboratory mice and genotyping of samples from most types of experimental crosses involving laboratory strains, particularly for reduced complexity crosses. The content of the production ver ... Full text Link to item Cite

Glycerol contributes to tuberculosis susceptibility in male mice with type 2 diabetes.

Journal Article Nat Commun · September 20, 2023 Diabetes mellitus increases risk for tuberculosis disease and adverse outcomes. Most people with both conditions have type 2 diabetes, but it is unknown if type 1 and type 2 diabetes have identical effects on tuberculosis susceptibility. Here we show that ... Full text Link to item Cite

Genome-wide screen identifies host loci that modulate Mycobacterium tuberculosis fitness in immunodivergent mice.

Journal Article G3 (Bethesda) · August 30, 2023 Featured Publication Genetic differences among mammalian hosts and among strains of Mycobacterium tuberculosis (Mtb) are well-established determinants of tuberculosis (TB) patient outcomes. The advent of recombinant inbred mouse panels and next-generation transposon mutagenesi ... Full text Link to item Cite

Mycobacterial Genetic Technologies for Probing the Host-Pathogen Microenvironment.

Journal Article Infect Immun · June 15, 2023 Featured Publication Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is one of the oldest and most successful pathogens in the world. Diverse selective pressures encountered within host cells have directed the evolution of unique phenotypic traits, resul ... Full text Link to item Cite

Differential Requirement for IRGM Proteins during Tuberculosis Infection in Mice.

Journal Article Infect Immun · February 16, 2023 Featured Publication Mycobacterium tuberculosis (Mtb) is a bacterium that exclusively resides in human hosts and remains a dominant cause of morbidity and mortality among infectious diseases worldwide. Host protection against Mtb infection is dependent on the function of immun ... Full text Link to item Cite

Mycobacterium tuberculosis Evasion of Guanylate Binding Protein-Mediated Host Defense in Mice Requires the ESX1 Secretion System.

Journal Article Int J Mol Sci · February 2, 2023 Cell-intrinsic immune mechanisms control intracellular pathogens that infect eukaryotes. The intracellular pathogen Mycobacterium tuberculosis (Mtb) evolved to withstand cell-autonomous immunity to cause persistent infections and disease. A potent inducer ... Full text Link to item Cite

An ancestral mycobacterial effector promotes dissemination of infection.

Journal Article Cell · November 23, 2022 Featured Publication The human pathogen Mycobacterium tuberculosis typically causes lung disease but can also disseminate to other tissues. We identified a M. tuberculosis (Mtb) outbreak presenting with unusually high rates of extrapulmonary dissemination and bone disease. We ... Full text Link to item Cite

Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication.

Journal Article Sci Signal · October 25, 2022 Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccin ... Full text Open Access Link to item Cite

Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice.

Journal Article Elife · February 3, 2022 Featured Publication The outcome of an encounter with Mycobacterium tuberculosis (Mtb) depends on the pathogen's ability to adapt to the variable immune pressures exerted by the host. Understanding this interplay has proven difficult, largely because experimentally tractable a ... Full text Link to item Cite

TMEM41B is a host factor required for the replication of diverse coronaviruses including SARS-CoV-2.

Journal Article PLoS Pathog · May 2021 Featured Publication Antiviral therapeutics are a front-line defense against virally induced diseases. Because viruses frequently mutate to escape direct inhibition of viral proteins, there is interest in targeting the host proteins that the virus must co-opt to complete its r ... Full text Link to item Cite

These Are the Genes You're Looking For: Finding Host Resistance Genes.

Journal Article Trends Microbiol · April 2021 Featured Publication Humanity's ongoing struggle with new, re-emerging and endemic infectious diseases serves as a frequent reminder of the need to understand host-pathogen interactions. Recent advances in genomics have dramatically advanced our understanding of how genetics c ... Full text Link to item Cite

Granulocytes act as a niche for Mycobacterium tuberculosis growth.

Journal Article Mucosal Immunol · January 2021 Granulocyte recruitment to the pulmonary compartment is a hallmark of progressive tuberculosis (TB). This process is well-documented to promote immunopathology, but can also enhance the replication of the pathogen. Both the specific granulocytes responsibl ... Full text Link to item Cite

The FDA-approved drug Alectinib compromises SARS-CoV-2 nucleocapsid phosphorylation and inhibits viral infection in vitro.

Journal Article bioRxiv · December 16, 2020 While vaccines are vital for preventing COVID-19 infections, it is critical to develop new therapies to treat patients who become infected. Pharmacological targeting of a host factor required for viral replication can suppress viral spread with a low proba ... Full text Link to item Cite

Content and Performance of the MiniMUGA Genotyping Array: A New Tool To Improve Rigor and Reproducibility in Mouse Research.

Journal Article Genetics · December 2020 The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and the ability to precisely manipulate its genome. Despite the importance of genetics for mouse resea ... Full text Link to item Cite

Distinct Bacterial Pathways Influence the Efficacy of Antibiotics against Mycobacterium tuberculosis.

Journal Article mSystems · August 4, 2020 Effective tuberculosis treatment requires at least 6 months of combination therapy. Alterations in the physiological state of the bacterium during infection are thought to reduce drug efficacy and prolong the necessary treatment period, but the nature of t ... Full text Link to item Cite

Mycobacterium tuberculosisevasion of Guanylate Binding Protein-mediated host defense in mice requires the ESX1 secretion system

Journal Article · 2020 Cell-intrinsic immune mechanisms control intracellular pathogens that infect eukaryotes. The intracellular pathogen Mycobacterium tuberculosis ( Mtb ) evolved to withstand cell-autonomous immunity to cause persistent infections and disease. A potent induce ... Full text Cite

Host-pathogen genetic interactions underlie tuberculosis susceptibility

Journal Article · 2020 The outcome of an encounter with Mycobacterium tuberculosis depends on the pathogen’s ability to adapt to the variable immune pressures exerted by the host. Understanding this interplay has proven difficult, largely because experimentally tractable animal ... Full text Cite

Functionally Overlapping Variants Control Tuberculosis Susceptibility in Collaborative Cross Mice.

Journal Article mBio · November 26, 2019 Host genetics plays an important role in determining the outcome of Mycobacterium tuberculosis infection. We previously found that Collaborative Cross (CC) mouse strains differ in their susceptibility to M. tuberculosis and that the CC042/GeniUnc (CC042) s ... Full text Open Access Link to item Cite

Statistical analysis of variability in TnSeq data across conditions using zero-inflated negative binomial regression.

Journal Article BMC Bioinformatics · November 21, 2019 BACKGROUND: Deep sequencing of transposon mutant libraries (or TnSeq) is a powerful method for probing essentiality of genomic loci under different environmental conditions. Various analytical methods have been described for identifying conditionally essen ... Full text Open Access Link to item Cite

Common Variants in the Glycerol Kinase Gene Reduce Tuberculosis Drug Efficacy.

Journal Article mBio · July 30, 2019 Despite the administration of multiple drugs that are highly effective in vitro, tuberculosis (TB) treatment requires prolonged drug administration and is confounded by the emergence of drug-resistant strains. To understand the mechanisms that limit antibi ... Full text Link to item Cite

Functionally overlapping variants control TB susceptibility in Collaborative Cross mice

Journal Article · 2019 Featured Publication Host genetics plays an important role in determining the outcome of Mycobacterium tuberculosis (Mtb) infection. We previously found that Collaborative Cross mouse strains differ in their susceptibility to Mtb, and that the CC042/GeniUnc (CC042) strain suff ... Full text Cite

Modeling Diversity: Do Homogeneous Laboratory Strains Limit Discovery?

Journal Article Trends Microbiol · November 2018 Featured Publication The outcome of chronic infections is highly variable. The heterogeneous disease outcomes in natural populations differ from genetically homogeneous infection models. Here, we use tuberculosis as a 'case study' to contrast the genetic landscape in natural p ... Full text Link to item Cite

The Phagocyte Oxidase Controls Tolerance to Mycobacterium tuberculosis Infection.

Journal Article J Immunol · September 15, 2018 Protection from infectious disease relies on two distinct strategies: antimicrobial resistance directly inhibits pathogen growth, whereas infection tolerance protects from the negative impact of infection on host health. A single immune mediator can differ ... Full text Link to item Cite

Statistical analysis of genetic interactions in Tn-Seq data.

Journal Article Nucleic Acids Res · June 20, 2017 Tn-Seq is an experimental method for probing the functions of genes through construction of complex random transposon insertion libraries and quantification of each mutant's abundance using next-generation sequencing. An important emerging application of T ... Full text Link to item Cite

Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis.

Journal Article Nat Microbiol · May 15, 2017 Nitric oxide contributes to protection from tuberculosis. It is generally assumed that this protection is due to direct inhibition of Mycobacterium tuberculosis growth, which prevents subsequent pathological inflammation. In contrast, we report that nitric ... Full text Link to item Cite

Griseofulvin impairs intraerythrocytic growth of Plasmodium falciparum through ferrochelatase inhibition but lacks activity in an experimental human infection study.

Journal Article Sci Rep · February 8, 2017 Griseofulvin, an orally active antifungal drug used to treat dermatophyte infections, has a secondary effect of inducing cytochrome P450-mediated production of N-methyl protoporphyrin IX (N-MPP). N-MPP is a potent competitive inhibitor of the heme biosynth ... Full text Link to item Cite

Tuberculosis Susceptibility and Vaccine Protection Are Independently Controlled by Host Genotype.

Journal Article mBio · September 20, 2016 Featured Publication UNLABELLED: The outcome of Mycobacterium tuberculosis infection and the immunological response to the bacillus Calmette-Guerin (BCG) vaccine are highly variable in humans. Deciphering the relative importance of host genetics, environment, and vaccine prepa ... Full text Open Access Link to item Cite

Tuberculosis susceptibility and vaccine protection are independently controlled by host genotype

Journal Article · 2016 The outcome of Mycobacterium tuberculosis (Mtb) infection and the immunological response to the Bacille Calmette Guerin (BCG) vaccine are highly variable in humans. Deciphering the relative importance of host genetics, environment, and vaccine preparation ... Full text Cite

Red cells from ferrochelatase-deficient erythropoietic protoporphyria patients are resistant to growth of malarial parasites.

Journal Article Blood · January 15, 2015 Many red cell polymorphisms are a result of selective pressure by the malarial parasite. Here, we add another red cell disease to the panoply of erythrocytic changes that give rise to resistance to malaria. Erythrocytes from individuals with erythropoietic ... Full text Link to item Cite

Treatment of erythrocytes with the 2-cys peroxiredoxin inhibitor, Conoidin A, prevents the growth of Plasmodium falciparum and enhances parasite sensitivity to chloroquine.

Journal Article PLoS One · 2014 The human erythrocyte contains an abundance of the thiol-dependant peroxidase Peroxiredoxin-2 (Prx2), which protects the cell from the pro-oxidant environment it encounters during its 120 days of life in the blood stream. In malarial infections, the Plasmo ... Full text Link to item Cite

Platelet factor 4 and Duffy antigen required for platelet killing of Plasmodium falciparum.

Journal Article Science · December 7, 2012 Platelets restrict the growth of intraerythrocytic malaria parasites by binding to parasitized cells and killing the parasite within. Here, we show that the platelet molecule platelet factor 4 (PF4 or CXCL4) and the erythrocyte Duffy-antigen receptor (Fy) ... Full text Link to item Cite

Host resistance to malaria: using mouse models to explore the host response.

Journal Article Mamm Genome · February 2011 Malaria is a disease that infects over 500 million people, causing at least 1 million deaths every year, with the majority occurring in developing countries. The current antimalarial arsenal is becoming dulled due to the rapid rate of resistance of the par ... Full text Link to item Cite