Digital Commons Network^™

Ganoderma Lucidum Reduces Obesity In Mice By Modulating The Composition Of The Gut Microbiota, Chih-Jung Chang, Chuan-Sheng Lin, Chia-Chen Lu, Jan Martel, Yun-Fei Ko, David M. Ojcius, Shun-Fu Tseng, Tsung-Ru Wu, Yi-Yuan Margaret Chen, John Ding-E. Young, Hsin-Chih Lai

All Dugoni School of Dentistry Faculty Articles

Obesity is associated with low-grade chronic inflammation and intestinal dysbiosis. Ganoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative anti-diabetic effects. Here, we show that a water extract of Ganoderma lucidum mycelium (WEGL) reduces body weight, inflammation and insulin resistance in mice fed a high-fat diet (HFD). Our data indicate that WEGL not only reverses HFD-induced gut dysbiosis—as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels—but also maintains intestinal barrier integrity and reduces metabolic endotoxemia. The anti-obesity and microbiota-modulating effects are transmissible via horizontal faeces transfer from WEGL-treated mice to HFD-fed mice. We further …

Cyclic Rhamnosylated Elongation Factor P Establishes Antibiotic Resistance In Pseudomonas Aeruginosa, Andrei Rajkovic, Sarah Erickson, Anne Witzky, Owen E. Branson, Jin Seo, Philip R. Gafken, Michael A. Frietas, Julian P. Whitelegge, Kym F. Faull, William Wiley Navarre, Andrew J. Darwin, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Elongation factor P (EF-P) is a ubiquitous bacterial protein that is required for the synthesis of poly-proline motifs during translation. In Escherichia coli and Salmonella enterica, the posttranslational β-lysylation of Lys34 by the PoxA protein is critical for EF-P activity. PoxA is absent from many bacterial species such as Pseudomonas aeruginosa, prompting a search for alternative EF-P posttranslation modification pathways. Structural analyses of P. aeruginosa EF-P revealed the attachment of a single cyclic rhamnose moiety to an Arg residue at a position equivalent to that at which β-Lys is attached to E. coli EF-P. Analysis of the genomes …

Expression, Localization, And Kinetic Characterization Of The Phospholipid Biosynthesis Enzyme Ctp: Phosphocholine Cytidylyltransferase From The Protozoan Parasite Leishmania Major, Justin Daniel Theodore Lange

Theses and Dissertations

The eukaryotic parasite Leishmania is the causative agent of the disease leishmaniasis. L. major is the most common of 21 species that causes visceral leishmaniasis in humans, and 30 that cause the same disease in other mammals. Visceral leishmaniasis causes fever, weight loss, and over a short amount of time, multiple organ failure, and has a 100% mortality rate within 2 years. This makes it the second largest parasitic killer in the world behind malaria. Over 90% of the worldâ??s cases of visceral leishmaniasis have been reported in underdeveloped countries of India, Bangladesh, Nepal, Sudan, Ethiopia and Brazil, with 500,000 …

Chronic Inflammation As A Result Of Hepatitis C Virus Infection: A Review Of The Literature, Samantha L. Lane

DePaul Discoveries

Approximately 170 million people are infected with Hepatitis C virus (HCV) worldwide^5,6. It is estimated that roughly 80% of those infected suffer from persistent infection with the virus; this persistence of infection is progressive, and over time can lead to fibrosis, cirrhosis, and hepatocellular carcinoma⁷. Chronic inflammation and apoptotic deregulation are both hallmarks of chronic HCV infection, and many molecular pathways are initiated in both the innate and adaptive immune responses during infection with this viral pathogen. The aim of this review was to survey some of the major molecular mechanisms responsible for the induction of …

Structural Elucidation Of Aggr-Activated Regulator, Aar, In Enteroaggregative Escherichia Coli, Andrew Heindel

Senior Honors Projects, 2010-2019

Travelers’ Diarrhea is the number one cause of childhood death in the world. Enteroaggregative Escherichia coli (EAEC) is one of the main causes of this disease. EAEC adhere to the surface of the intestine and stack in a brick-like pattern. Via an unstudied quorum-sensing mechanism, these bacteria express a variety of virulence factors that lead to diarrhea. The long-term goal of this research is to elucidate the mechanism by which EAEC changes from benign to virulent. A previously-unstudied open-reading frame in EAEC, AggR activated repressor (Aar), has recently been hypothesized to act as one of the major transcription factors influencing …

Section Abstracts: Biology With Microbiology And Molecular Biology

Virginia Journal of Science

Abstracts of the Biology with Microbiology and Molecular Biology Section for the 93rd Annual Meeting of the Virginia Academy of Science, May 21-23, 2015, James Madison University, Richmond, Virginia

Structural And Functional Interactions Between Bro1 Domain Of Human Alix Protein And Nucleocapsid Packaging Rna Complex From Hiv, Scott Gross

Graduate School of Biomedical Sciences Theses and Dissertations

A virus is only as powerful as its ability to spread. Enveloped retroviruses, namely HIV-1, use exocytosis pathways that normal host cells use to release particles from the plasma membrane. The main pathways of interest in this study are the Endosomal Sorting Complex Required for Transport (ESCRT) and adjacent ALIX pathways. The ESCRT pathway is especially important for degradation of receptor/cargo complexes that form Multi-Vesicular Bodies (MVBs). Currently, there is no known therapy that targets this endosomal pathway, which would prevent the spread of the virus to other cells. The virus has adapted to jump from pathway to pathway when …

A Multilaboratory Comparison Of Calibration Accuracy And The Performance Of External References In Analytical Ultracentrifugation, Huaying Zhao, Rodolfo Ghirlando, Carlos Alfonso, Fumio Arisaka, Ilan Attali, David L. Bain, Et Al. ..., Donald F. Becker, Peter Schuck

Department of Biochemistry: Faculty Publications

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy …

Phenotypic And Functional Genomics Analyses Of Salmonella For Food Safety Applications, Turki Dawoud

Graduate Theses and Dissertations

Non-typhoidal Salmonella species have been major foodborne zoonotic pathogens causing serious problems in public health and food industry for several decades. Numerous Salmonella species have frequently been associated with different food commodities mainly poultry meat, eggs, and their products. This dissertation begins with a literature reviews discussing many aspects of Salmonella generally; and subsequently focused on two serotypes, Salmonella Enteritidis and S. Typhimurium as they are at the top of all other serovars responsible for most illness cases and outbreaks. In addition, some Salmonella strains have exhibited their ability to tolerate and survive many food processing treatments. We can divide …

Osteomyelitis Associated With Nocardiopsis Composta In A Dog, Elisa N. Salas, Debra Royal, Lance Kurz, J. Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Osteomyelitis can be caused by bacterial or fungal agents or may be idiopathic. Cocci, bacilli, and filamentous bacteria such as members of the Actinomycetes have all been determined to be causes of osteomyelitis. Differential diagnoses for Gram-positive filamentous rods in the family Actinomycetales causing osteomyelitis in the dog, include members of the more frequently encountered genera Nocardia and Actinomyces. Bacteria gain access to the bone via several routes but are most often associated with direct inoculation (such as percutaneous injuries, compound fractures, or secondary to foreign bodies such as surgical or other material including dirt and wood) and fracture …

The Effect Of Activation Induced Cytidine Deaminase Phosphorylation And Herpes Virus Uracil Dna Glycosylase On Antibody Diversification, Marc Macaluso

Dissertations and Theses (Open Access)

Activation-induced cytidine deaminase (AID) is a mutagenic enzyme that is expressed in mammalian B-cells and initiates the antibody diversification processes of somatic hypermuntation (SHM) and isotype class switch recombination (CSR). AID is targeted to the immunoglobulin gene locus where it deaminates cytosines to generate uracil residues in DNA. This generates guanine-uracil (U:G) mismatch lesion which are recognized by uracil DNA glycosylase (UNG), a DNA repair enzyme that removes uracil from DNA and triggers downstream repair of the lesion. While UNG is a ubiquitously expressed DNA repair enzyme, its recognition and removal of AID introduced uracils is essential in both SHM …

Selection Methods For Genetically-Modified T Cells: In Support Of Translational Therapy, David Rushworth

Dissertations and Theses (Open Access)

T cells are blood cells which organize the immune system of the host. These cells are necessary for the host to respond appropriately to threats from foreign organisms and cancerous growth. However, in the case of certain infections and cancer, T cells are unable to respond appropriately to a threat and establish immunity. This leads to disease when the infection or cancer is not sufficiently eliminated. On the other hand, T cells can lack tolerance for healthy tissue and perceive healthy tissue as infected. The ensuing over-reactive immune response also leads to disease. A delicate balance must exist between immunity …

Development Of Genetic Goat And Hamster Models Of Atrial Fibrillation And Long Qt Syndrome; And Genetic Hamster Models Of Middle East Respiratory Syndrome, Dane A. Rasmussen

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Atrial fibrillation (AF) and long QT syndrome (LQTS) are potentially lethal heart rhythm disorders that can be caused by mutations in the potassium channel gene KCNQ1. Middle East Respiratory Syndrome (MERS) is a viral infection with the potential to replicate the devastating effects of the SARS outbreak in 2003. All three of these diseases are in need of genetic animal models.

To address these needs, my thesis project focused on the development of genetic goat and hamster models of AF and LQTS, and genetic hamster models of MERS. Because of the goat’s similar organ size/physiology and the hamster’s similar lipid …

Whole Genome Comparison Of A Large Collection Of Mycobacteriophages Reveals A Continuum Of Phage Genetic Diversity, Welkin H. Pope, Charles A. Bowman, Daniel A. Russell, Deborah Jacobs-Sera, David J. Asai, Steven G. Cresawn, William R. Jacobs Jr, Roger W. Hendrix, Jeffrey G. Lawrence, Graham F. Hatfull, Dr. Kathleen Cornely

Chemistry & Biochemistry Faculty Publications

The bacteriophage population is large, dynamic, ancient, and genetically diverse. Limited genomic information shows that phage genomes are mosaic, and the genetic architecture of phage populations remains ill-defined. To understand the population structure of phages infecting a single host strain, we isolated, sequenced, and compared 627 phages of Mycobacterium smegmatis. Their genetic diversity is considerable, and there are 28 distinct genomic types (clusters) with related nucleotide sequences. However, amino acid sequence comparisons show pervasive genomic mosaicism, and quantification of inter-cluster and intra-cluster relatedness reveals a continuum of genetic diversity, albeit with uneven representation of different phages. Furthermore, rarefaction analysis shows …

Aggregatibacter Actinomycetemcomitans Cytolethal Distending Toxin Activates The Nlrp3 Inflammasome In Human Macrophages Leading To The Release Of Pro-Inflammatory Cytokines, Bruce J. Shenker, David M. Ojcius, Lisa P. Walker, Ali Zekavat, Monika Damek Scuron, Kathleen Boesze-Battaglia

All Dugoni School of Dentistry Faculty Articles

The cytolethal distending toxin (Cdt) is produced from a number of bacteria capable of causing infection and inflammatory disease. Our previous studies with Actinobacillus actinomycetemcomitans Cdt demonstrate not only that the active toxin subunit functions as a phosphatidylinositol-3,4,5-triphosphate (PIP3) phosphatase but also that macrophages exposed to the toxin were stimulated to produce proinflammatory cytokines. We now demonstrate that the Cdt-induced proinflammatory response involves the activation of the NLRP3 inflammasome. Specific inhibitors and short hairpin RNA (shRNA) were employed to demonstrate requirements for NLRP3 and ASC as well as caspase-1. Furthermore, Cdt-mediated inflammasome activation is dependent upon upstream signals, including reactive …

Adenovirus Entry From The Apical Surface Of Polarized Epithelia Is Facilitated By The Host Innate Immune Response, Poornima L.N. Kotha, Priyanka Sharma, Abimbola O. Kolawole, Ran Yan, Mahmoud Alghamri, Trisha L. Brockman, Julian Gomez-Cambronero, Julian Cambronero

Biological Sciences Faculty Publications

Prevention of viral-induced respiratory disease begins with an understanding of the factors that increase or decrease susceptibility to viral infection. The primary receptor for most adenoviruses is the coxsackievirus and adenovirus receptor (CAR), a cell-cell adhesion protein normally localized at the basolateral surface of polarized epithelia and involved in neutrophil transepithelial migration. Recently, an alternate isoform of CAR, CAREx8, has been identified at the apical surface of polarized airway epithelia and is implicated in viral infection from the apical surface. We hypothesized that the endogenous role of CAR^Ex8 may be to facilitate host innate immunity. We show that IL-8, …

Relationship Between Heat-Labile Enterotoxin Secretion Capacity And Virulence In Wild Type Porcine-Origin Enterotoxigenic Escherichia Coli Strains, Prageeth Wijemanne, Jun Xing, Emil M. Berberov, David B. Marx, David H. Francis, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

Heat-labile enterotoxin (LT) is an important virulence factor secreted by some strains of enterotoxigenic Escherichia coli (ETEC). The prototypic human-origin strain H10407 secretes LT via a type II secretion system(T2SS). We sought to determine the relationship between the capacity to secrete LT and virulence in porcine-origin wild type (WT) ETEC strains. Sixteen WT ETEC strains isolated from cases of severe diarrheal disease were analyzed by GM1ganglioside enzyme- linked immunosorbent assay tomeasure LT concentrations in culture supernatants. All strains had detectable LT in supernatants by 2 h of culture and 1 strain, which was particularly virulent in gnotobiotic piglets (3030-2), had …

Environmental Microbes And Uveitis: Is Microbial Exposure Always Bad?, Chandirasegaran Massilamany, A. Gangaplara, J. Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

The eye generally is considered to be an immune-privileged organ, but this notion is being increasingly challenged as ocular antigens can be expressed in the generative lymphoid organs, resulting in attainment of self-tolerance. What triggers a break in this tolerant state is a fundamental question in autoimmunity research. The general belief is that exposure to environmental microbes can break self-tolerance in genetically susceptible individuals, leading to the induction of autoimmune responses. The molecular mimicry hypothesis has been proposed as one major mechanistic, pathway through which microbes, by generating crossreactive immune responses, can induce ocular damage of the kind that might …

Analysis Of Cathepsin And Furin Proteolytic Enzymes Involved In Viral Fusion Protein Activation In Cells Of The Bat Reservoir Host, Farah El Najjar, Levi Lampe, Michelle L. Baker, Lin-Fa Wang, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Bats of different species play a major role in the emergence and transmission of highly pathogenic viruses including Ebola virus, SARS-like coronavirus and the henipaviruses. These viruses require proteolytic activation of surface envelope glycoproteins needed for entry, and cellular cathepsins have been shown to be involved in proteolysis of glycoproteins from these distinct virus families. Very little is currently known about the available proteases in bats. To determine whether the utilization of cathepsins by bat-borne viruses is related to the nature of proteases in their natural hosts, we examined proteolytic processing of several viral fusion proteins in cells derived from …

A Quick Guide For Building A Successful Bioinformatics Community., Aidan Budd, Manuel Corpas, Michelle D Brazas, Jonathan C Fuller, Jeremy Goecks, Nicola J Mulder, Magali Michaut, B F Francis Ouellette, Aleksandra Pawlik, Niklas Blomberg

Computational Biology Institute

"Scientific community" refers to a group of people collaborating together on scientific-research-related activities who also share common goals, interests, and values. Such communities play a key role in many bioinformatics activities. Communities may be linked to a specific location or institute, or involve people working at many different institutions and locations. Education and training is typically an important component of these communities, providing a valuable context in which to develop skills and expertise, while also strengthening links and relationships within the community. Scientific communities facilitate: (i) the exchange and development of ideas and expertise; (ii) career development; (iii) coordinated funding …

Trail-Based High Throughput Screening Reveals A Link Between Trail-Mediated Apoptosis And Glutathione Reductase, A Key Component Of Oxidative Stress Response., Dmitri Rozanov, Anton Cheltsov, Eduard Sergienko, Stefan Vasile, Vladislav Golubkov, Alexander E Aleshin, Trevor Levin, Elie Traer, Byron Hann, Julia Freimuth, Nikita Alexeev, Max A Alekseyev, Sergey P Budko, Hans Peter Bächinger, Paul Spellman

Computational Biology Institute

A high throughput screen for compounds that induce TRAIL-mediated apoptosis identified ML100 as an active chemical probe, which potentiated TRAIL activity in prostate carcinoma PPC-1 and melanoma MDA-MB-435 cells. Follow-up in silico modeling and profiling in cell-based assays allowed us to identify NSC130362, pharmacophore analog of ML100 that induced 65-95% cytotoxicity in cancer cells and did not affect the viability of human primary hepatocytes. In agreement with the activation of the apoptotic pathway, both ML100 and NSC130362 synergistically with TRAIL induced caspase-3/7 activity in MDA-MB-435 cells. Subsequent affinity chromatography and inhibition studies convincingly demonstrated that glutathione reductase (GSR), a key …

Composition, Taxonomy And Functional Diversity Of The Oropharynx Microbiome In Individuals With Schizophrenia And Controls., Eduardo Castro-Nallar, Matthew L Bendall, Marcos Pérez-Losada, Sarven Sabuncyan, Emily G Severance, Faith B Dickerson, Jennifer R Schroeder, Robert H Yolken, Keith A Crandall

Computational Biology Institute

The role of the human microbiome in schizophrenia remains largely unexplored. The microbiome has been shown to alter brain development and modulate behavior and cognition in animals through gut-brain connections, and research in humans suggests that it may be a modulating factor in many disorders. This study reports findings from a shotgun metagenomic analysis of the oropharyngeal microbiome in 16 individuals with schizophrenia and 16 controls. High-level differences were evident at both the phylum and genus levels, with Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria dominating both schizophrenia patients and controls, and Ascomycota being more abundant in schizophrenia patients than controls. Controls …

Stress Management In Cyst-Forming Free-Living Protists: Programmed Cell Death And/Or Encystment, Naveed Ahmed Khan, Junaid Iqbal, Ruqaiyyah Siddiqui

Department of Biological & Biomedical Sciences

In the face of harsh conditions and given a choice, a cell may (i) undergo programmed cell death, (ii) transform into a cancer cell, or (iii) enclose itself into a cyst form. In metazoans, the available evidence suggests that cellular machinery exists only to execute or avoid programmed cell death, while the ability to form a cyst was either lost or never developed. For cyst-forming free-living protists, here we pose the question whether the ability to encyst was gained at the expense of the programmed cell death or both functions coexist to counter unfavorable environmental conditions with mutually exclusive phenotypes.

Characterization Of A Novel Protease In Staphylococcus Aureus, Adam L. Johnson

Theses and Dissertations

A newly discovered cysteine protease, Prp, has been shown to perform an essential, site-specific cleavage of ribosomal protein L27 in Staphylococcus aureus. In Firmicutes and related bacteria, ribosomal protein L27 is encoded with a conserved N-terminal extension that must be removed to expose residues critical for ribosome function. Uncleavable and pre-cleaved variants were unable to complement an L27 deletion in S. aureus, indicating that this N-terminal processing event is essential and likely plays an important regulatory role. The gene encoding the responsible protease (prp) has been shown to be essential, and is found in all organisms …

The Role Of Rnai In Downregulation Of Physcomitrella Patens Defense Genes And The Preliminary Steps Of Peg Mediated Transformation Of Mosses, Adam Beswick

Undergraduate Honors Thesis Collection

When attacked by a pathogen, the moss Physcomitrella patens will undergo both a hypersensitive response (HR) as well as a systematic acquired resistance (SAR) response. The SAR response turns on genes that ready the plant for future pathogen attacks. The hormone jasmonic acid (JA) is one of the products of SAR response in P. patens. In this study interference RNA (RNAi) was used to decrease gene expression of the allene oxide cyclase (ACe) gene, a key gene in the production pathway of JA. Using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), RNAi was found to significantly lower ACC gene levels …

Francisella Tularensis Catalase Restricts Immune Function By Impairing Trpm2 Channel Activity, Nicole Lynn Flaherty

Legacy Theses & Dissertations (2009 - 2024)

As an innate defense mechanism, macrophages produce reactive species that weaken pathogens and serve as secondary messengers to modify signaling responses involved in immune function. The gram-negative bacterium F. tularensis utilizes its antioxidant armature to limit the host immune response but the mechanism behind this suppression has not been defined. Here we establish that F. tularensis limits Ca2+ entry thereby limiting actin reorganization and IL-6 production in a redox-dependent fashion. Wild-type (LVS) or catalase deficient F. tularensis (∆katG) show distinct profiles in their H2O2 scavenging capacity, 1 pM/sec and 0.015 pM/sec, respectively. Murine alveolar macrophages infected with ∆katG display distinct …

Genome-Scale Analyses Of Transcription And Transcriptional Regulation In Bacteria, Devon Marie Fitzgerald

Legacy Theses & Dissertations (2009 - 2024)

The textbook model of bacterial transcription regulation posits that promoters occur immediately upstream of genes and that transcription factors (TFs) modulate transcription through promoter-proximal binding. However, the recent application of unbiased genome-wide approaches, such as ChIP-seq and RNA-seq, has revealed a much more complex picture, including TF binding and transcription initiation occurring in unexpected locations. This dissertation describes the use of deep sequencing-based approaches to evaluate the genome-wide binding of transcription-related proteins and identify locations of transcription initiation. I have assessed the genome-wide binding of three Escherichia coli TFs and an alternative σ factor. Additionally, I have analyzed genome-wide patterns …

Relationship Between Heat-Labile Enterotoxin Secretion Capacity And Virulence In Wild Type Porcine-Origin Enterotoxigenic Escherichia Coli Strains, Prageeth Wijemanne, Jun Xing, Emil M. Berberov, David H. Francis, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

Heat-labile enterotoxin (LT) is an important virulence factor secreted by some strains of enterotoxigenic Escherichia coli (ETEC). The prototypic human-origin strain H10407 secretes LT via a type II secretion system(T2SS). We sought to determine the relationship between the capacity to secrete LT and virulence in porcine-origin wild type (WT) ETEC strains. Sixteen WT ETEC strains isolated from cases of severe diarrheal disease were analyzed by GM1ganglioside enzyme- linked immunosorbent assay tomeasure LT concentrations in culture supernatants. All strains had detectable LT in supernatants by 2 h of culture and 1 strain, which was particularly virulent in gnotobiotic piglets (3030-2), had …

Temperatures Of Storage Areas In Large Animal Veterinary Practice Vehicles In The Summer And Comparison With Drug Manufacturers’ Storage Recommendations, Jeff D. Ondrak, Meredyth L. Jones, Virginia R. Fajt

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Large animal veterinarians carry drugs in their practice vehicles in storage areas that are not typically refrigerated. The most common upper limits of manufacturers’ storage temperatures for United States (U.S.)-approved non-refrigerated drugs are 25 or 30 °C. Because ambient temperatures in many locations in the U.S. exceed these temperatures during the summer, we measured storage area temperatures over 4 months in the summer of 2013 to evaluate the extent to which labeled storage temperatures are exceeded.

Methods: A convenience sample of 12 vehicles from 5 central Texas practices and 12 vehicles from 4 south central Nebraska practices was …

Development Of Novel Fluorescent Tools For Investigating Virulence Factors And Drug Susceptibility In Mycobacterium Tuberculosis, Kaley Wilburn

HIM 1990-2015

Mycobacterium tuberculosis (Mtb) is the causative agent of Tuberculosis (TB), a life-threatening disease primarily affecting the lungs that infects about one third of the world's population and causes 1.3 million deaths annually. It is estimated that TB has been infecting humans for around 70,000 years and has killed more people than any other infectious disease. The highly effective, persistent, and multifaceted virulence strategies that have allowed Mtb to continue to spread and thrive for so long are still poorly understood at the molecular level. This lack of knowledge contributes to ongoing challenges to curing TB. Although drugs capable of killing …