Lesson 20. Mycobacterium
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USMLE – What's It
Purpose of this handout Congratulations on making it to Year 2 of medical school! You are that much closer to having your Doctor of Medicine degree. If you want to PRACTICE medicine, however, you have to be licensed, and in order to be licensed you must first pass all four United States Medical Licensing Exams. This book is intended as a starting point in your preparation for getting past the first hurdle, Step 1. It contains study tips, suggestions, resources, and advice. Please remember, however, that no single approach to studying is right for everyone. USMLE – What is it for? In order to become a licensed physician in the United States, individuals must pass a series of examinations conducted by the National Board of Medical Examiners (NBME). These examinations are the United States Medical Licensing Examinations, or USMLE. Currently there are four separate exams which must be passed in order to be eligible for medical licensure: Step 1, usually taken after the completion of the second year of medical school; Step 2 Clinical Knowledge (CK), this is usually taken by December 31st of Year 4 Step 2 Clinical Skills (CS), this is usually be taken by December 31st of Year 4 Step 3, typically taken during the first (intern) year of post graduate training. Requirements other than passing all of the above mentioned steps for licensure in each state are set by each state’s medical licensing board. For example, each state board determines the maximum number of times that a person may take each Step exam and still remain eligible for licensure. -
Immunology of Tuberculosis
Color code: Important in red Extra in blue Immunology of Tuberculosis Editing file Objectives ➢ To know how M. tuberculosis infection is contracted and its initial encounter with the immune system ➢ To understand the delayed type of hypersensitivity reaction against M. tuberculosis ➢ To be familiar with the possible outcomes of the infection with M. tuberculosis in immunocompetent and immunocompromised hosts ➢ To understand the basis of the tuberculin test and its importance in gauging immunity against M. tuberculosis Introduction to Tuberculosis ➢ Mycobacterium tuberculosis is the second most common infectious cause of death in adults worldwide, with an increasing incidence due to HIV. ➢ TB is transmitted through aerosols (airborne transmission) by coughing or sneezing and acquired mainly through inhalation. ➢ The clinical development of the disease depends solely on the effectiveness of the host’s innate and adaptive immune response to the infection. If the immune response is functioning well, the clinical disease has little to no chance of developing. Tuberculosis is able to withstand the body’s immune response after being phagocytosed by several ways, including: Virulence factors Host factors The lipid-rich Waxy outer coat blocks Resistance to reactive oxygen intermediates. phagocytic enzymes. Catalase-peroxidase resists the host cell Inhibition of phagosome-lysosome fusion oxidative response. The glycolipid Lipoarabinomannan (LAM) Inhibition of phagosome acidification. Stimulates cytokines, resists the host oxidative (prevents digestion -
Antibitoic Treatment for Tuberculosis Induces a Profound Dysbiosis of the Gut Microbiome That Persists Long After Therapy Is Completed
ANTIBITOIC TREATMENT FOR TUBERCULOSIS INDUCES A PROFOUND DYSBIOSIS OF THE GUT MICROBIOME THAT PERSISTS LONG AFTER THERAPY IS COMPLETED A Thesis Presented to the Faculty of the Weill Cornell Graduate School of Medical Sciences in Partial Fulfillment of the Requirements for the Degree of Masters of Science by Matthew F. Wipperman May 2017 © 2017 Matthew F. Wipperman ABSTRACT Mycobacterium tuberculosis, the cause of Tuberculosis (TB), infects one third of the world’s population and causes substantial mortality worldwide. In its shortest format, treatment of drug sensitive TB requires six months of multidrug therapy with a mixture of broad spectrum and mycobacterial specific antibiotics, and treatment of multidrug resistant TB is much longer. The widespread use of this regimen worldwide makes this one the largest exposures of humans to antimicrobials, yet the effects of antimycobacterial agents on intestinal microbiome composition and long term stability are unknown. We compared the microbiome composition, assessed by both 16S rDNA and metagenomic DNA sequencing, of Haitian TB cases during antimycobacterial treatment and following cure by 6 months of TB therapy. TB treatment does not perturb overall diversity, but nonetheless dramatically depletes multiple immunologically significant commensal bacteria. The perturbation by TB therapy lasts at least 1.5 years after completion of treatment, indicating that the effects of TB treatment are long lasting and perhaps permanent. These results demonstrate that TB treatment has dramatic and durable effects on the intestinal microbiome and highlight unexpected extreme consequences of treatment for the world’s most common infection on human ecology. BIOGRAPHICAL SKETCH NAME POSITION TITLE Wipperman, Matthew Frederick Postdoctoral Researcher at eRA COMMONS USER NAME Memorial Sloan Kettering Cancer Center MFWIPPERMAN DEGREE INSTITUTION AND (if MM/YY FIELD OF STUDY LOCATION applicable) Franklin & Marshall College B.A. -
Mapping Interactions of Microbial Metabolites and Human Receptors
bioRxiv preprint doi: https://doi.org/10.1101/614537; this version posted May 2, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Classification: Biological Sciences - Microbiology Title: Mapping interactions of microbial metabolites and human receptors Authors: 1Dominic A. Colosimo, 1Jeffrey A. Kohn, 1Peter M. Luo, 3Sun M. Han, 2AmanDa J. PickarD, 2Arka Rao, 2Justin R. Cross, 3Louis J. Cohen, 1Sean F. BraDy* Author affiliation: 1Laboratory of Genetically EncoDeD Small Molecules, The Rockefeller University, 1230 York Avenue, New York City, NY 10065. 2DonalD B. anD Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York City NY 10065, USA. 3Division of Gastroenterology, Department of MeDicine, Icahn School of MeDicine at Mount Sinai, New York City, NY 10029, USA. *Corresponding Authors Sean F. BraDy Contact: Laboratory of Genetically EncoDeD Small Molecules The Rockefeller University 1230 York Avenue New York, NY 10065 Phone: 212-327-8280 Fax: 212-327-8281 Email: [email protected] Acknowledgements: All bacterial strains were generously proviDeD by Daniel MuciDa. High-resolution mass spectrometry of purifieD compounDs was performeD by Rockefeller University Proteomics Core. We are grateful to C. Fermin, E. Vazquez, anD G. Escano in the Precision Immunology Institute at the Icahn School of MeDicine at Mount Sinai (PrIISM) Gnotobiotic facility anD Microbiome Translational Center for their help with gnotobiotic experiments. FunDing was proviDeD by the Bill anD MelinDa Gates FounDation (OPP1168674) anD the National Institutes of Health (5R01AT009562–02). Keywords: primary metabolites, human microbiome, G-protein coupleD receptors Author Contributions: D.A.C., L.J.C. -
Diarylcoumarins Inhibit Mycolic Acid Biosynthesis and Kill Mycobacterium Tuberculosis by Targeting Fadd32
Diarylcoumarins inhibit mycolic acid biosynthesis and kill Mycobacterium tuberculosis by targeting FadD32 Sarah A. Stanleya,b,c, Tomohiko Kawatea,b,c, Noriaki Iwasea,b,c, Motohisa Shimizua,b,c, Anne E. Clatworthya,b,c, Edward Kazyanskayaa, James C. Sacchettinid, Thomas R. Ioergere, Noman A. Siddiqif, Shoko Minamif, John A. Aquadroa, Sarah Schmidt Granta,b,c, Eric J. Rubinf, and Deborah T. Hunga,b,c,1 aInfectious Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA 02142; bDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114; cDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; Departments of dBiochemistry and Biophysics and eComputer Science, Texas A&M University, College Station, TX 77843; and fDepartment of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115 Edited* by John J. Mekalanos, Harvard Medical School, Boston, MA, and approved May 30, 2013 (received for review February 1, 2013) Infection with the bacterial pathogen Mycobacterium tuberculosis not yet in clinical trials, include Benzothiazinones that target imposes an enormous burden on global public health. New anti- decaprenylphosphoryl-β-d-ribose 2′-epimerase (DprE1) (2) and biotics are urgently needed to combat the global tuberculosis inhibitors of malate synthase, a glyoxylate shunt enzyme (10). In pandemic; however, the development of new small molecules is addition to their potential as drug candidates, these molecules hindered by a lack of validated drug targets. Here, we describe the are significant for having facilitated the identification of novel identification of a 4,6-diaryl-5,7-dimethyl coumarin series that kills targets for further efforts geared toward drug discovery. -
Neisseria Obligate Aerobe Usmle
Neisseria Obligate Aerobe Usmle Unreverent Steward coruscate very effectually while Olin remains unpitied and asclepiadaceous. Antiphrastic Remus rejoiced reportedly or predestining huffishly when Mohammed is brainier. How Latin is Aubert when genitival and woozier Barney gritted some dominee? Journal will cause a handy way down the obligate aerobe bacteria are notorious smallpox virus vaccine development Mechanism and their use clinical features is untreated, confirmed by tsetse fly, david i speak about viruses. By neisseria gonorrhea. Chlamydiae are obligate aerobes. Progresses rapidly and include biochemical foundations of obligate aerobe? Nearby is poorly immunogenic in development caused by hermann eibel. Which one vial should be classified as early sign in order shipped on. The bacterium can be monitored regularly for national microbiology laboratory screening after being affected most often causes no. Like receptor protein structures or conjunctival infections that binds siderophores. The obligate aerobes can improve treatment for misconfigured or diploid cells with their own atp? Gonococcal infections are obligate aerobe? Intracellular pathogen releases verotoxin, which is less important microorganisms is a mechanism of microbiology, give aspirin or disseminated infections. Dna into facebook confirmed results on their fe transport systems used for diagnostic testing are out fermentation for her unfailing devotion. The following are modeled to another bacterium, ascending gonococcal infections, and liver or with alkaline urine sample for fe can be more than the four days of all treatment. Key differences between cells may be visualized by entrance of electrical signals skin flora. Shigella sonnei with lecturio offers and decide how do stick or jump right lobe diagnosis. Recognition proteins cell and neisseria meningitidis, motor or stored as confirmation with symptoms. -
Hadd, a Novel Fatty Acid Synthase Type II Protein, Is Essential for Alpha- and Epoxy-Mycolic Acid Biosynthesis and Mycobacterial
www.nature.com/scientificreports OPEN HadD, a novel fatty acid synthase type II protein, is essential for alpha- and epoxy-mycolic acid Received: 9 November 2017 Accepted: 3 April 2018 biosynthesis and mycobacterial Published: xx xx xxxx ftness Cyril Lefebvre1, Richard Boulon1, Manuelle Ducoux2, Sabine Gavalda1, Françoise Laval1, Stevie Jamet1, Nathalie Eynard1, Anne Lemassu1, Kaymeuang Cam1, Marie-Pierre Bousquet2, Fabienne Bardou1, Odile Burlet-Schiltz2, Mamadou Dafé1 & Annaïk Quémard1 Mycolic acids (MAs) have a strategic location within the mycobacterial envelope, deeply infuencing its architecture and permeability, and play a determinant role in the pathogenicity of mycobacteria. The fatty acid synthase type II (FAS-II) multienzyme system is involved in their biosynthesis. A combination of pull-downs and proteomics analyses led to the discovery of a mycobacterial protein, HadD, displaying highly specifc interactions with the dehydratase HadAB of FAS-II. In vitro activity assays and homology modeling showed that HadD is, like HadAB, a hot dog folded (R)-specifc hydratase/ dehydratase. A hadD knockout mutant of Mycobacterium smegmatis produced only the medium-size alpha’-MAs. Data strongly suggest that HadD is involved in building the third meromycolic segment during the late FAS-II elongation cycles, leading to the synthesis of the full-size alpha- and epoxy-MAs. The change in the envelope composition induced by hadD inactivation strongly altered the bacterial ftness and capacities to aggregate, assemble into colonies or bioflms and spread by sliding motility, and conferred a hypersensitivity to the frstline antimycobacterial drug rifampicin. This showed that the cell surface properties and the envelope integrity were greatly afected. With the alarmingly increasing case number of nontuberculous mycobacterial diseases, HadD appears as an attractive target for drug development. -
Unique Characteristic Features of Mycobacterium Tuberculosis in Relation to Immune System
American Journal of Immunology 7 (1): 1-8, 2011 ISSN 1553-619X © 2011 Science Publications Unique Characteristic Features of Mycobacterium Tuberculosis in Relation to Immune System Rajni and Laxman S. Meena Institute of Genomics and Integrative Biology, Allergy and Infectious Diseases, Mall Road, Delhi-110007, India Abstract: Problem statement: Tuberculosis is a leading global mortality factor which has not been effectively controlled, with 1.7 million deaths per year and 8.9 million new cases. Aerobic microbe Mycobacterium Tuberculosis H37Rv (MTB) is the causative agent of tuberculosis. Approach: It is unique among prokaryotes due to its exceptional features contributing to its survival within the hostile environment of macrophages. Results: It modifies both its intracellular and local tissue environment and proliferates within macrophages resulting in caseous granulomas, the characteristic lesions of TB. MTB derived cAMP intoxicates host cells and thus enable MTB for long term persistence within macrophages by modifying its intracellular environment. Apart from these, there are several unique structural components of MTB which interfere in the pathways of immune system and thus eluding it from destruction. Conclusion: The dormant state of MTB is the major factor which provides this pathogen ability to survive host inflammatory mediators and antibiotic treatment. It is indispensable to delineate the unusual features of MTB that enable its escape from the host immune system, in order to design an efficacious drug against the unpardonable form of tuberculosis. Key words: Unique characteristic, mycobacterium tuberculosis , immune system, survive host, multidrug resistant, virulence factors, resistant tuberculosis, sharply reduced, drug resistant INTRODUCTION Tuberculosis is caused by Mycobacterium Tuberculosis H37Rv (MTB) which is a unique acid fast Tuberculosis is the directing cause of death gram positive bacterium. -
The Mycobacterial Cell Envelope: a Relict from the Past Or the Result of Recent Evolution?
fmicb-09-02341 October 10, 2018 Time: 14:51 # 1 PERSPECTIVE published: 09 October 2018 doi: 10.3389/fmicb.2018.02341 The Mycobacterial Cell Envelope: A Relict From the Past or the Result of Recent Evolution? Antony T. Vincent1,2, Sammy Nyongesa1, Isabelle Morneau3, Michael B. Reed2,4,5, Elitza I. Tocheva3 and Frederic J. Veyrier1,2* 1 INRS-Institut Armand-Frappier, Bacterial Symbionts Evolution, Laval, QC, Canada, 2 McGill International TB Centre, Montreal, QC, Canada, 3 Faculty of Dentistry, Université de Montréal, Montreal, QC, Canada, 4 Department of Medicine, McGill University, Montreal, QC, Canada, 5 Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada Mycobacteria are well known for their taxonomic diversity, their impact on global health, and for their atypical cell wall and envelope. In addition to a cytoplasmic membrane and a peptidoglycan layer, the cell envelope of members of the order Corynebacteriales, which include Mycobacterium tuberculosis, also have an arabinogalactan layer Edited by: Christoph Mayer, connecting the peptidoglycan to an outer membrane, the so-called “mycomembrane.” Eberhard Karls Universität Tübingen, This unusual cell envelope composition of mycobacteria is of prime importance for Germany several physiological processes such as protection from external stresses and for Reviewed by: virulence. Although there have been recent breakthroughs in the elucidation of the Andreas Burkovski, Friedrich-Alexander-Universität composition and organization of this cell envelope, its evolutionary origin remains Erlangen-Nürnberg, Germany a mystery. In this perspectives article, the characteristics of the cell envelope of Patrick Joseph Moynihan, University of Birmingham, mycobacteria with respect to other actinobacteria will be dissected through a molecular United Kingdom evolution framework in order to provide a panoramic view of the evolutionary pathways Hesper Rego, that appear to be at the origin of this unique cell envelope. -
Clinical Aspects of Blastomycosis
Thorax: first published as 10.1136/thx.25.6.708 on 1 November 1970. Downloaded from Thorax (1970), 25, 708. Clinical aspects of blastomycosis RICHARD P. O'NEILL and ROBERT W. B. PENMAN Department of Medicine, University of Kentucky Medical Center, Lexington, Kentucky Blastomycosis is a specific granulomatous disease which tends to be chronic and indolent. It frequently presents in extrapulmonary form by means of haematogenous dissemination from the lungs. It has been shown that tuberculosis, histoplasmosis and coccidioidomycosis are, in the majority of cases, mild and subclinical in effect and often heal without therapy. It is probable that blastomycosis behaves in a like manner. The exact mortality is not known but is probably in the range of 13% in hospitalized cases with disseminated disease (Blastomycosis Cooperative Study of the Veterans Administration, 1964). The most effective form of therapy in active disease is amphotericin B; 2-hydroxy-stilbamidine is also used. Blastomycosis has largely been considered to be a disease of the American continent. However, cases have been reported from Africa and Europe and therefore a wider appreciation of this disease is considered pertinent. The relevant literature has been reviewed and four illustrative cases are presented. North American blastomycosis was first described 100,000 population (Furcolow et al., 1966). How- by Gilchrist in 1896 in a report of a case which ever, recent studies have shown previously un- had previously been diagnosed as 'pseudolupus recognized, widely separated areas of endemic copyright. vulgaris' and had been thought to be tuberculous blastomycosis. Seven cases have been reported in origin. Gilchrist showed that the disease was from Africa; two from the Congo (Gatti, caused by a specific organism, Blastomyces derma- Renoirte, and Vandepitte, 1964; Gatti, De Broe, titidis. -
Mycolic Acid (M4537)
Mycolic acid from Mycobacterium tuberculosis (bovine strain) Catalog Number M4537 Storage Temperature –20 °C CAS RN 37281-34-8 Due to the high lipid content of the cell wall, mycobacteria do not stain well with Gram stain Product Description techniques. Heat and a solvent such as phenol are Among different groups of bacteria (e.g., Gram-positive, required for stains to penetrate mycobacteria. Once Gram-negative, spirochetes, mycobacteria, and stained, however, the bacteria retain the stain even mycoplasma), there are various types of cell envelopes when flooded with mineral acids and alcohols. This that represent a departure from the normal simplicity of ability to retain stains after acid washings defines bacterial cell structure compared to animal cells. acid-fast bacteria. Included among the components of the mycobacterium The impermeable cell wall impedes the entry of cell envelope are the cytoplasmic membrane, the cell nutrients causing mycobacteria to grow slowly, but the wall, and the capsule. The cytoplasmic membrane is a low permeability also contributes to the organism’s high phospholipid bilayer unit membrane similar to that resistance to chemical agents and resistance to found in eukaryotic cells. Overlaying the cytoplasmic lysosomal digestion by phagocytes. membrane is a structure consisting of a number of polymers called the cell wall. As for most types of Successful lysis of Mycobacterium tuberculosis by bacteria, highly crosslinked peptidoglycan is a phagocytes causes the release of mycolic acid. The component of the cell wall. Surrounding the cell wall is mycolic acid molecules bind to receptors on an outer layer called the capsule consisting of macrophages causing them to release cytokines such polysaccharide and protein with traces of lipid.1 as tumor necrosis factor-alpha (TNF-a). -
Deletion of a Dehydratase Important for Intracellular Growth and Cording
Deletion of a dehydratase important for intracellular PNAS PLUS growth and cording renders rough Mycobacterium abscessus avirulent Iman Hallouma, Séverine Carrère-Kremerb,c, Mickael Blaisea, Albertus Viljoena, Audrey Bernuta, Vincent Le Moigned, Catherine Vilchèzee,f, Yann Guérardelg, Georges Lutfallah, Jean-Louis Herrmannd, William R. Jacobs Jr.e,f,1, and Laurent Kremera,i,1 aCentre d’études d’agents Pathogènes et Biotechnologies pour la Santé (CPBS), CNRS Formation de Recherche en Evolution 3689, 34293 Montpellier, France; bINSERM U1058, Université de Montpellier, Montpellier 34095, France; cDepartment of Bacteriology–Virology, Centre Hospitalo-Universitaire de Montpellier, Montpellier 34095, France; dUMR1173, INSERM, Université de Versailles St. Quentin, 78180 Montigny le Bretonneux, France; eDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; fHoward Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461; gUniversity of Lille, CNRS, UMR 8576, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), 59000 Lille, France; hLaboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, CNRS UMR5235, Université Montpellier, 34293 Montpellier, France; and iINSERM, CPBS, 34293 Montpellier, France Contributed by William R. Jacobs Jr., June 2, 2016 (sent for review February 17, 2016; reviewed by R. Andres Floto and Todd A. Gray) Mycobacterium abscessus (Mabs) is a rapidly growing Mycobacterium lungs of patients with underlying lung disorders such as cystic and an emerging pathogen in humans. Transitioning from a smooth fibrosis (10) but also causes skin and soft tissue infections in (S) high-glycopeptidolipid (GPL) producer to a rough (R) low-GPL immunocompetent individuals (11). Mabs can exhibit a rough producer is associated with increased virulence in zebrafish, which in- (R) or a smooth (S) morphotype, depending on the absence or volves the formation of massive serpentine cords, abscesses, and rapid presence of surface-associated glycopeptidolipids (GPLs) (12, 13).