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Full-Text Articles in Medical Sciences
Evolution And Genetic Diversity In Streptococcus Pneumoniae, Diana Lee Dupraw
Evolution And Genetic Diversity In Streptococcus Pneumoniae, Diana Lee Dupraw
All ETDs from UAB
The relative contributions of point mutations and intergenomic recombination via lateral gene transfer (LGT) determine the population structure and evolutionary style for a given bacterial species. Streptococcus pneumoniae has a weakly clonal population structure; adaptive clonal complexes can be detected; however, these can also be rapidly lost due to the high rate of recombination. To characterize the diversity of pneumococcal isolates in clonal complex, and to elucidate possible mechanisms for the long-term stability of such complexes, 35 serotype 6B strains belonging to a previously identified clonal complex, CC14, were assayed by Comparative Genome Hybridization (CGH) and Multi Locus Sequence Typing …
The Role Of Toll-Like Receptors 2 And 4 In Helicobacter Felis Infections And Asthma, Carolyn Durham
The Role Of Toll-Like Receptors 2 And 4 In Helicobacter Felis Infections And Asthma, Carolyn Durham
All ETDs from UAB
The inverse correlation between the industrialization and disease prevalence is termed the "hygiene hypothesis." Supporting this, immunological studies show Th1 cytokines modulate Th2 immune responses. Because the mucosa is essential in antigenic exposure, understanding bacterial sensing here is critical to addressing three foundations of this hypothesis: the role of bacterial exposure, relevance of noninvasive bacterial exposure, and influence of these exposures on immune responses. Key components of antigen sensing in the mucosa are toll-like receptors (TLRs) 2 and 4, which have been implicated in disease. The hypothesis of this thesis is, by globally knocking out one or both of these …
Brms1 Coordinately Regulates Microrna To Suppress Breast, Mick D. Edmonds
Brms1 Coordinately Regulates Microrna To Suppress Breast, Mick D. Edmonds
All ETDs from UAB
The majority of cancer related mortality is attributed to complications associated with metastatic disease. Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis of multiple cancer types in vivo and loss of nuclear BRMS1 is associated with ER-negative cancers and a high rate of proliferation. Many groups have shown BRMS1 to regulate the expression of multiple metastatic genes, yet until now no one has been able to account for how these many changes in gene expression occur. In this work, we report that BRMS1 regulates a select set of genes called microRNA (miRNA), and these miRNA themselves can regulate metastasis. Using …
Preclinical Pharmacology Of Novel Synthetic Iminoquinones As Anticancer Agents, Scharri Ezell
Preclinical Pharmacology Of Novel Synthetic Iminoquinones As Anticancer Agents, Scharri Ezell
All ETDs from UAB
Prostate cancer is the most common male malignancy and the second leading cause of cancer related death in the United States. Despite recent advances in the detection, diagnosis, and treatment of prostate cancer, there is a need for more effective therapies. Unfortunately, most conventional therapeutic modalities, such as androgen ablation therapy, frequently result in androgen-independent cancers. These cancers are typically more aggressive, metastatic, and resistant to chemotherapeutic agents than androgen-dependent prostate cancer. Therefore, agents that are effective against both androgen-sensitive and androgen-independent, as well as genetically diverse cancers are critically needed. The objective of the dissertation research was to address …
Mechanisms Of Major Outer Membrane Protein (Momp)-Vaccine Induced Protective Immunity Against Chlamydia Muridarum Genital Infection, Christina M. Farris
Mechanisms Of Major Outer Membrane Protein (Momp)-Vaccine Induced Protective Immunity Against Chlamydia Muridarum Genital Infection, Christina M. Farris
All ETDs from UAB
Urogenital infection with Chlamydia trachomatis is the most common bacterial sexually transmit-ted disease with an estimated 90 million new infections occurring each year worldwide. In women infection with C. trachomatis can result in serious complications including ectopic pregnancy, pelvic inflammatory disease and tubal factor infertility. Despite very effective antimicrobial chemotherapy, control of the infection will likely require an effective vaccine. We have assessed the protective effect of an outer membrane based vaccine using a murine model of chlamydial genital tract infection. Female mice were vaccinated with C. muridarum major outer membrane protein (MOMP) plus the immunostimulatory adjuvants CpG-1826 and Montanide …
Identification And Validation Of Biodosimetry Markers In Multiple Models Of Radiation Exposure, Ashley Nicole Filiano
Identification And Validation Of Biodosimetry Markers In Multiple Models Of Radiation Exposure, Ashley Nicole Filiano
All ETDs from UAB
Following a radiological or nuclear disaster, radiation dose assessment is imperative to minimize morbidity and mortality through rationally directed medical intervention. Current methods of retrospective dosimetry are not amenable to mass exposure scenarios and remain limited to monitoring of clinical symptoms (nausea/vomiting and lymphocyte depletion) and cytogenetic analysis. The goal of this study was to identify radiation biomarkers capable of qualitative (non-irradiated/irradiated) and quantitative (dose) assessment of radiation exposure. Initial analyses revealed 17 radiation-responsive cytokine/chemokine genes in blood samples from 6 pediatric cancer patients undergoing fractionated total body irradiation (TBI). These 17 genes were combined with 29 additional IR-inducible genes …
Poxvirus Evolution: The Role Of Horizontal Gene Transfer, Mary Rebecca Odom
Poxvirus Evolution: The Role Of Horizontal Gene Transfer, Mary Rebecca Odom
All ETDs from UAB
We have investigated the set of all poxvirus proteins for information about the origins of protein coding genes of the Poxviridae family of viruses. A global assessment of all poxvirus proteins for levels of similarity to proteins of other organisms, including eukaryotes, viruses, and prokaryotes, has suggested trends and relationships informative about poxvirus evolution and poxvirus interactions with hosts. Our research has focused on the poxvirus proteins subset this assessment identified as likely to have evolutionary histories involving horizontal gene transfer (HGT). We have used phylogenetic reconstructions to individually determine the sources of more than 70 horizontally transferred genes present …
A Nucleolar Specificity Factor For E2f1 Induced Cell Death, Jason Chang Paik
A Nucleolar Specificity Factor For E2f1 Induced Cell Death, Jason Chang Paik
All ETDs from UAB
The E2F family of transcription factors are important regulators of cell proliferation, and are often dysregulated in cancers. One member of the E2F family, E2F1, also has the ability to induce apoptosis; therefore, uncovering how E2F1-induced apoptosis is controlled is of interest in understanding tumorigenesis. To this end, we identified RRP1B as a novel target specifically induced by E2F1. RRP1B expression is specifically upregulated by E2F1 overexpression, but not other E2F family members. RRP1B expression is correlated with E2F1 expression during the cell cycle, and is significantly induced after DNA damage. The minimal RRP1B promoter region responsive to E2F1 was …
Regulation Of Vascular Smooth Muscle Cell Signaling And Metabolism By Platelet-Derived Growth Factor, Jessica Perez
Regulation Of Vascular Smooth Muscle Cell Signaling And Metabolism By Platelet-Derived Growth Factor, Jessica Perez
All ETDs from UAB
Growth factors are important inducers of vascular cell growth whose regulation is altered during the pathogenesis of atherosclerosis. An increase in growth factor and cytokine production, as well as lipid oxidation is observed in cardiovascular disease (CVD) and contributes to altered vascular cell signaling, exacerbated atherosclerotic lesions and heart failure. A change in cellular bioenergetic status due to mitochondrial dysfunction or damage has also been noted in CVD. In this thesis, we first examine cell signaling pathways in vascular smooth muscle cells (VSMC) which are activated in response to platelet-derived growth factor (PDGF) and regulate the cell cycle protein changes …
Heparanase Drives The Aggressive Myeloma Phenotype: Preclinical Development Of A Heparanase Inhibitor For The Treatment Of Multiple Myeloma, Joe Ritchie
All ETDs from UAB
Heparanase, an endoglycosidase which cleaves heparan sulfate chains at specific sites, is rarely expressed in normal tissues but becomes evident in many human cancers. We have previously shown that heparanase promotes myeloma growth and angiogenesis through modulation of the tumor microenvironment. Recognition that heparanase drives the aggressive myeloma phenotype has led to new strategies designed to therapeutically target this enzyme. SST0001, a non-anticoagulant heparin that is 100% N-acetylated and 25% glycol split, was previously described as a potent inhibitor of heparanase activity in vitro, and, in limited in vivo experiments, SST0001 was identified to have efficacy as an anti-tumor agent …
Lens Cataract: Biochemical Analysis Of The Alpha Crystallins, David Ray Stella
Lens Cataract: Biochemical Analysis Of The Alpha Crystallins, David Ray Stella
All ETDs from UAB
The cataract is a common ailment affecting the aged population. It appears over time and affects the quality of one’s life by the eventual loss of vision. Currently, there is no effective strategy to prevent or treatment to reverse the development of a cataract. As well, there is no consensus on one particular mechanism or sequence of events that contributes to its formation. In order to better understand the possible etiology of the cataract, it is necessary to define the biochemical changes that occur to lens proteins as one ages, as these are the key players in the prevention of …
Exosomal Curcumin: Its Bioavailability And Potential Anti-Inflammation Activity, Dongmei Sun
Exosomal Curcumin: Its Bioavailability And Potential Anti-Inflammation Activity, Dongmei Sun
All ETDs from UAB
Curcumin, a pleiotropic polyphenol derived from turmeric plants Curcuma Longa with rhizome, exhibits strong evidence as an anti-inflammation, anti-oxidant and anti-cancer reagent both in vitro and in vivo. Due to its low stability and systemic bioavailability, a large amount of curcumin has to be administrated to achieve therapeutic effects both in animal and in human. The major effort to overcome this barrier is making by encapsulation of curcumin into nanoparticles such as polymers and liposomes; some promising data have demonstrated the effectiveness of such method. Exosomes are vesicle-like nanoparticles secreted by living cells. Exosomes contain both cell surface molecules and …
Dna Replication And Cytokinesis In Drosophila Melanogaster, Anton Svitin
Dna Replication And Cytokinesis In Drosophila Melanogaster, Anton Svitin
All ETDs from UAB
DNA replication and cytokinesis are two important parts of the cell division process. Our studies address different aspects of both of these processes and potential links between them. One of the best approaches for studying DNA replication in eukaryotes has been an analysis in cell free in vitro systems. The existing cell free replication systems for Drosophila are relatively ineffective. In the first part of this work, we have developed an optimized in vitro system to study DNA replication using early egg extracts of Drosophila. Our studies indicate that this system proves to be an extremely useful tool for a …
Structural And Functional Study Of P58(Ipk), Jiahui Tao
Structural And Functional Study Of P58(Ipk), Jiahui Tao
All ETDs from UAB
P58(IPK) is an endoplasmic reticulum (ER)-resident protein which is upregulated during unfolded protein response (UPR). In stressed cells, P58(IPK) functions to restore protein folding equilibrium in ER by suppressing protein aggregation and promoting protein folding. P58(IPK) associates with the unfolded protein via its N-terminal TPR domain and presents it to BiP (binding immunoglobulin protein) for subsequent folding. P58(IPK) belongs to the Hsp40 family. Collectively, P58(IPK) is a stress-inducible ER-resident molecular chaperone. In this dissertation, we report the crystal structure of P58(IPK) TPR domain to 2.5 Å resolution. In the crystal structure, the 43-kDa TPR domain consists of nine tandemly linked …
Roles Of Adiponectin And Its Receptors In Foam Cell Transformation, Ling Tian
Roles Of Adiponectin And Its Receptors In Foam Cell Transformation, Ling Tian
All ETDs from UAB
Macrophages play a critical role in the initiation and progression of atherosclerosis by producing pro-inflammatory mediators and transforming into lipid-laden foam cells. The prevention of lipid accumulation and inflammation in macrophage foam cells, therefore, represents a promising target for effective therapy for atherosclerosis. Adiponectin is a circulating cytokine primarily expressed and secreted by adipocytes, and is downregulated in obesity-linked diseases including type 2 diabetes, coronary artery disease and hypertension. In oxidized low-density lipoprotein (oxLDL)-induced human THP-1 macrophage foam cells, adiponectin suppresses lipid accumulation through decreasing lipid uptake and increasing high-density lipoprotein (HDL)-mediated lipid efflux. The potential mechanisms that adiponectin utilizes …
Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer, Heather Nicole Tinsley
Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer, Heather Nicole Tinsley
All ETDs from UAB
Breast cancer remains a major health concern, despite efforts to develop improved therapeutics. Chemoprevention is a promising strategy for reducing breast cancer-related morbidity and mortality. However, with the exception of the selective estrogen receptor modulators (SERMs), which have limited efficacy and severe toxicities, no drugs have been approved for breast cancer chemoprevention. Studies demonstrate that certain nonsteroidal anti-inflammatory drugs (NSAIDs) display promising chemopreventive efficacy. Unfortunately, the depletion of physiologically important prostaglandins due to inhibition of the cyclooxygenase (COX) enzymes results in potentially fatal toxicities, which exclude the use of NSAIDs and COX-2 selective inhibitors for chemoprevention. Ample data, however, suggest …
Red Blood Cell And Hemoglobin Dependent Modulation Of Reactive Species Metabolism: Implications For Vascular Homeostasis, Dario A. Vitturi
Red Blood Cell And Hemoglobin Dependent Modulation Of Reactive Species Metabolism: Implications For Vascular Homeostasis, Dario A. Vitturi
All ETDs from UAB
The recent discovery that red blood cells might mediate hypoxic blood flow together with accumulating evidence that suggests a role for the modulation of vascular inflammation has reshaped the way we think about the function of these cells. In this thesis we investigate the mechanisms that regulate these newly appreciated functions and focus on i) the ability of red cells to couple oxygen sensing with nitrite reduction and nitric oxide formation and ii) the role of the beta93cys, a conserved residue amongst mammalian hemoglobins and whose function remains unclear. Data will be presented that demonstrate that nitrite reduction to nitric …
Usp14: A Link Between The Proteasome And Synaptic Function, Brandon John Walters
Usp14: A Link Between The Proteasome And Synaptic Function, Brandon John Walters
All ETDs from UAB
The ubiquitin proteasome system (UPS) is a coordinated process by which the cell can control protein distribution and abundance. Proteins are marked for turnover by the construction of a polyubiquitin chain on the protein substrate. Once engaged by the proteasome, the ubiquitin side-chain is disassembled by proteasomal deubiquitinating enzymes (DUBs), preventing entry of ubiquitin into the proteasome and recycling it for use in future reactions. One of the DUBs that resides on the proteasome is Ubiquitin Specific Protease 14 (Usp14), which is mutated in the ataxia (axJ) mice. This mutation results in pronounced physical deficits and, unexpectedly, a deficit in …
A Dual Protease Inhibitor/Receptor Antagonist With Therapeutic Implications For Chronic Inflammatory Lung Diseases, Matthew Thomas Hardison
A Dual Protease Inhibitor/Receptor Antagonist With Therapeutic Implications For Chronic Inflammatory Lung Diseases, Matthew Thomas Hardison
All ETDs from UAB
Chronic neutrophilic inflammation is a hallmark of numerous pulmonary diseases. It is commonly associated with declining lung function, collagen turnover, and increased protease activity. Our laboratory has recently published several articles describing a biologically active collagen breakdown product, proline-glycine-proline (PGP) and its more active amino-terminus acetylated form, N-α-PGP. PGP acts via classical chemokine receptors CXCR1 and 2 to draw neutrophils (PMNs) into sites of inflammation in what is potentially a feed-forward mechanism of disease. The tri-peptide appears to be a bio-marker in certain clinical diseases like cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The present work first details …
Functional Determinants Of The Porin Mspa And Its Role In Permeabilizing Mycobacterial Outer Membranes, Jason Huff
Functional Determinants Of The Porin Mspa And Its Role In Permeabilizing Mycobacterial Outer Membranes, Jason Huff
All ETDs from UAB
Mycobacterium tuberculosis (Mtb) infects one third of the global population and causes approximately 2,000,000 Tuberculosis-related deaths annually. Mycobacteria are Gram positive organisms but contain a unique outer membrane (OM) which is functionally similar but structurally different from those of Gram negative bacteria. The mycobacterial OM presents an efficient permeability barrier towards hydrophilic solutes. Slow permeation kinetics of hydrophilic molecules through membranes and several discoveries of cell wall channel-forming proteins indicate that mycobacterial OMs are functionalized by proteins. MspA is the primary porin of M. smegmatis and mediates diffusion of small, hydrophilic nutrients and antibiotics across the OM. Unlike porins of …
Role Of The Human Cytomegalovirus Tegument Protein Pp150 In The Trafficking And Assembly Of Infectious Virions, Sabarish Vellatheri Indran
Role Of The Human Cytomegalovirus Tegument Protein Pp150 In The Trafficking And Assembly Of Infectious Virions, Sabarish Vellatheri Indran
All ETDs from UAB
Human cytomegalovirus, a ubiquitous human pathogen, establishes a persistent infection in the infected host. HCMV assembly takes place in the nucleus and cytoplasm of infected cells by a complex and incompletely defined process. The viral DNA is enclosed by the capsid, which is surrounded by a proteinaceous tegument, which is covered by a cell-derived envelope studded with viral glycoproteins. The assembly pathway and protein interactions required for formation of the tegument layer and the function of most of the proteins in the tegument remain poorly understood. In this study, we investigated the functions of an essential abundant tegument protein, pp150, …
Molecular Mechanisms Of Hepatic Insulin Resistance Following Injury, Shaoning Jiang
Molecular Mechanisms Of Hepatic Insulin Resistance Following Injury, Shaoning Jiang
All ETDs from UAB
Insulin resistance commonly occurs following injuries or critical illness independent of previous diabetic status. The development of insulin resistance and hyperglycemia is associated with increased mortality and morbidity in critically ill patients. However, the molecular mechanisms underlying the acute insulin resistance following injuries remain poorly understood. With an animal model of trauma and hemorrhage, we have previously demonstrated the rapid development of insulin resistance in liver, and a critical role of TNFα in hemorrhage-induced defects in insulin signaling following resuscitation. However, hepat-ic insulin signaling is impaired prior to a significant increase in plasma TNFα, suggesting the initial development of hemorrhage-induced …
In Vitro Elucidation Of The Role And Mechanism Of Rankl In Tnf-And Il-1-Mediated Osteoclast Formation And Function, Joel Jules
All ETDs from UAB
The receptor activator of NF-қB (RANK) ligand (RANKL) and its receptor RANK play a critical role in osteoclast biology. RANK has three tumor necrosis factor receptor associated factor (TRAF)-binding motifs [PFQEP369-373 (Motif 1), PVQEET559-564 (Motif 2), and PVQEQG604-609 (Motif 3)] that regulate osteoclast formation and function. RANK also contains a TRAF-independent motif (IVVY535-538) that commits bone marrow macrophages (BMMs), which are osteoclast precursors, to the osteoclast lineage for osteoclastogenesis. Notably, tumor necrosis factor-α (TNF) and interlukin-1 (IL-1) utilize TRAFs to initiate most of the signaling pathways known to be activated by RANKL but fail to form osteoclasts unless attended by …
Identification And Characterization Of Downstream Target Genes Of The Bmp Signaling Pathway, Nam Chul Kim
Identification And Characterization Of Downstream Target Genes Of The Bmp Signaling Pathway, Nam Chul Kim
All ETDs from UAB
During nervous system development, neurons proliferate, differentiate, project their axons to their targets and make synapses with them. At the neuromuscular junction of Drosophila, these functional synapses enlarge as the body grows to maintain physiologically effective synaptic transmission with the muscles. Drosophila Bone Morphogenetic Protein (BMP) type II receptor, Wishful thinking (Wit), is important in this proper synaptic growth and function. To identify transcriptional targets of Wit signaling, we performed microarray experiments comparing normal controls to wit mutants. Through this study, we found that some of the verified target genes showed isoform-specific regulation in wit mutants, and that several neuropeptide …
The Role Of The Intracellular Signaling Pathway In Ehrlichia Canis Infection In Vitro, Chang-Hyun Kim
The Role Of The Intracellular Signaling Pathway In Ehrlichia Canis Infection In Vitro, Chang-Hyun Kim
All ETDs from UAB
Ehrlichia canis is a pleomorphic obligatory intracellular gram-negative bacterium that causes tick-borne canine ehrlichiosis. A systematic investigation on the pathogenesis of the disease has been hindered largely by lack of a reliable quantitative assay. Using quantitative real time PCR (qPCR), a quantitative assay for E. canis was developed and validated. Using the qPCR, the intracellular proliferation kinetics of E. canis in the canine 030F cell-line was studied for the first time. Many intracellular bacterial pathogens have been shown to use Ca2+ signaling in the host cells to induce their own internalization and proliferation. However, it is not clear how Ca2+ …
Transcriptional Regulation Of The Human Heme Oxygenase-1 Via Chromatin Looping In Renal Cells, Junghyun Kim
Transcriptional Regulation Of The Human Heme Oxygenase-1 Via Chromatin Looping In Renal Cells, Junghyun Kim
All ETDs from UAB
Heme oxygenase-1 (HO-1) is a critical enzyme catalyzing the degradation of heme and generating carbon monoxide, iron, and biliverdin. In addition to heme degradation, HO-1 expression is known to protect against various cellular insults and disease states including acute kidney injury, atherosclerosis, vascular restenosis, and others. Human HO-1 gene expression is tightly regulated at the level of transcription. The main goal of this study is to explore the transcriptional regulation of the human HO-1 gene in renal epithelial cells. Chromosome Conformation Capture (3C) demonstrates that multiple regulatory regions within the HO-1 promoter and enhancer regions are physically interacting with each …
The Role Of Gli1 In Eralpha-Negative Breast Cancer: Promoting Survival, Migration, Invasion, And Metastasis, Yeon-Jin Kwon
The Role Of Gli1 In Eralpha-Negative Breast Cancer: Promoting Survival, Migration, Invasion, And Metastasis, Yeon-Jin Kwon
All ETDs from UAB
Glioma-associated oncogene homolog 1 (Gli1) is a well-known oncogene and a transcription factor that mediates several signaling pathways important for tumor progression, such as hedgehog, TGFß, Ras, and EGFR. Although Gli1 is known to play an important role in cancers of brain, skin, prostate, and the pancreas, the role of Gli1 in breast cancer was not previously well-defined. Therefore, this dissertation focuses on defining the role of Gli1 and the mechanism underlying Gli1-mediated transcription in breast cancer. Interestingly, the major findings of the dissertation clearly indicate that Gli1 promotes cell survival and is predictive of a poor outcome in Estrogen …
Effect Of Overexpressing Apolipoprotein A-I In An Animal Model Of Alzheimer's Disease, Terry L. Lewis
Effect Of Overexpressing Apolipoprotein A-I In An Animal Model Of Alzheimer's Disease, Terry L. Lewis
All ETDs from UAB
Apolipoprotein A-I (apoA-I) is the major protein component of high density lipoprotein (HDL) in circulation and is expressed mainly by the liver and intestine. The levels of apoA-I/HDL are inversely related to the incidence of cardiovascular disease. Because of the connections between heart disease and Alzheimer's disease (AD), it is conceivable that high levels of apoA-I/HDL may be protective against AD. However, the limited literature shows mixed results on the role of apoA-I/HDL in the development of AD. It is hypothesized that increased expression of human apoA-I will ameliorate the behavioral deficits and characteristic amyloid-ß (Aß) plaque formation in a …
Role Of 14-3-3&Tau In Autophagy And Role Of Edd In P53 Regulation, Shiyun Ling
Role Of 14-3-3&Tau In Autophagy And Role Of Edd In P53 Regulation, Shiyun Ling
All ETDs from UAB
Unrestricted cell proliferation and suppression of cell death are two essential events for tumor development. My dissertation research involves two proteins, 14-3-3 &tau and EDD which are involved in diverse pathways related to these two fields in recent studies. Previous study demonstrates that 14-3-3ô regulates p21 degradation. Up-regulation of 14-3-3ô is seen in breast cancer and is correlated with the down-regulation of p21 in breast cancer. Amplification or overexpression of EDD was observed in breast cancer and ovarian cancers. Illustrating the new roles of these two proteins in proliferation and cell death will advance our knowledge in tumorigenesis and help …
Developing A Screen To Identify Small Molecule Inhibitors That Disrupt Protein-Protein Interactions In Mycobacteria, Deborah Mai
Developing A Screen To Identify Small Molecule Inhibitors That Disrupt Protein-Protein Interactions In Mycobacteria, Deborah Mai
All ETDs from UAB
Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB) and infects nearly one-third of the world's population. The same TB chemotherapeutic regimen has been administered for more than 50 years, and can be improved by developing innovative methods to discover new anti-TB drugs. This work describes a newly established high-throughput screen (HTS) platform technology based on Mycobacterial-Protein Fragment Complementation (M-PFC) to identify small molecule inhibitors of protein-protein interactions in mycobacteria. M-PFC HTS employs both whole cell and target-based approaches, and offers flexibility in selecting an appropriate protein interaction target for HTS. Selectable drug targets can include interactions of essential …