DOCSLIB.ORG

Characterization of Coxiella Burnetii Outbreak Strains

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Characterization of Coxiella Burnetii Outbreak Strains Characterization of Coxiella burnetii outbreak strains Runa Kuley Characterization of Coxiella burnetii outbreak strains Thesis committee Promotors Prof. Dr M.A. Smits Professor of Intestinal Health of Animals Runa Kuley Wageningen University & Research Prof. Dr J.M. Wells Professor of Host-Microbe Interactomics Wageningen University & Research Co-promotor Dr A. Bossers Senior Scientist, Department of Infection Biology Thesis Wageningen University & Research submitted in fulfilment of the requirements for the degree of doctor at Wageningen University Other members by the authority of the Rector Magnificus Prof. Dr. H.F.J. Savelkoul, Wageningen University & Research Prof. Dr A.P.J. Mol, Prof. Dr J.P.M. van Putten, Utrecht University in the presence of the Dr A.L. Zomer, Utrecht University Thesis Committee appointed by the Academic Board Dr C.A.W. Klaassen, Erasmus MC Rotterdam to be defended in public on Monday May 8, 2017 This research was conducted under the auspices of the Graduate School of Wageningen Institute of at 4 p.m. in the Aula. Animal Sciences (WIAS). Characterization of Coxiella burnetii outbreak strains Thesis committee Promotors Prof. Dr M.A. Smits Professor of Intestinal Health of Animals Runa Kuley Wageningen University & Research Prof. Dr J.M. Wells Professor of Host-Microbe Interactomics Wageningen University & Research Co-promotor Dr A. Bossers Senior Scientist, Department of Infection Biology Thesis Wageningen University & Research submitted in fulfilment of the requirements for the degree of doctor at Wageningen University Other members by the authority of the Rector Magnificus Prof. Dr. H.F.J. Savelkoul, Wageningen University & Research Prof. Dr A.P.J. Mol, Prof. Dr J.P.M. van Putten, Utrecht University in the presence of the Dr A.L. Zomer, Utrecht University Thesis Committee appointed by the Academic Board Dr C.A.W. Klaassen, Erasmus MC Rotterdam to be defended in public on Monday May 8, 2017 This research was conducted under the auspices of the Graduate School of Wageningen Institute of at 4 p.m. in the Aula. Animal Sciences (WIAS). Runa Kuley Characterization of Coxiella burnetii outbreak strains, 226 pages PhD thesis, Wageningen University, Wageningen, NL (2017) With references, with summary in English and Dutch ISBN 978-94-6343-151-4 DOI 10.18174/410829 Runa Kuley Characterization of Coxiella burnetii outbreak strains, 226 pages PhD thesis, Wageningen University, Wageningen, NL (2017) With references, with summary in English and Dutch ISBN 978-94-6343-151-4 DOI 10.18174/410829 Contents Chapter 1: General introduction and thesis outline 9 Chapter 2: Cell-free propagation of Coxiella burnetii does not affect its relative virulence. 37 Chapter 3: Major differential gene regulation in Coxiella burnetii between in vivo and in 59 vitro cultivation models Chapter 4: First complete genome sequence of the Dutch veterinary Coxiella burnetii 85 strain NL3262, originating from the largest global Q fever outbreak, and draft genome sequence of its epidemiologically linked chronic human isolate NLhu3345937 Chapter 5: Plasticity and polymorphisms in critical genes correlate with increased 93 virulence of Dutch outbreak-related Coxiella burnetii strains Chapter 6: Coxiella burnetii strain specific immune responses are more depending on host 131 origin than on MLVA genotype classification. Chapter 7: Coxiella burnetii isolates originating from infected cattle induce a more 155 pronounced pro-inflammatory cytokine response compared to isolates from infected goats and sheep. Chapter 8: General discussion 177 Summary 197 Samenvatting 203 Curriculum vitae 211 Acknowledgements 217 Training and supervision plan 223 Colophon 226 Contents Chapter 1: General introduction and thesis outline 9 Chapter 2: Cell-free propagation of Coxiella burnetii does not affect its relative virulence. 37 Chapter 3: Major differential gene regulation in Coxiella burnetii between in vivo and in 59 vitro cultivation models Chapter 4: First complete genome sequence of the Dutch veterinary Coxiella burnetii 85 strain NL3262, originating from the largest global Q fever outbreak, and draft genome sequence of its epidemiologically linked chronic human isolate NLhu3345937 Chapter 5: Plasticity and polymorphisms in critical genes correlate with increased 93 virulence of Dutch outbreak-related Coxiella burnetii strains Chapter 6: Coxiella burnetii strain specific immune responses are more depending on host 131 origin than on MLVA genotype classification. Chapter 7: Coxiella burnetii isolates originating from infected cattle induce a more 155 pronounced pro-inflammatory cytokine response compared to isolates from infected goats and sheep. Chapter 8: General discussion 177 Summary 197 Samenvatting 203 Curriculum vitae 211 Acknowledgements 217 Training and supervision plan 223 Colophon 226 Chapter 1 General introduction and thesis outline Chapter 1 General introduction and thesis outline Chapter 1 General Introduction Q fever disease Coxiella burnetii is the etiological agent of Q fever; a worldwide zoonotic disease that can result in C. burnetii infects a broad range of hosts, but infections are wide-spread in domestic ruminants [8,9]. large outbreaks in humans. In the recent years, there has been an immense improvement in our Among these, goats, sheep and cattle are the primary reservoirs of the pathogen and represent the most understanding of both the biology and pathogenicity of C. burnetii. However very little is known frequent source of human infection [10]. Infections in animals are assumed to occur mostly by about the molecular mechanisms involved in its interaction with hosts. In addition, only a few inhalation of the pathogen from the environment and are often asymptomatic [11]. The disease virulence factors have been identified and biologically validated. Virulence factors of this pathogen symptoms are usually manifested in pregnant animals and widely differ between hosts [8,10,12]. In most likely include determinants promoting its survival and replication in hostile intracellular pregnant goats and sheep, the main clinical manifestations are abortions at final gestation stage. environments and facilitating manipulation or evasion of host immune responses. Hence, the Infected cattle usually do not show symptoms although abortions, subfertility and metritis are seen in molecular characterization of C. burnetii isolates is essential for virulence factor analysis, some cases [13]. Abortions in infected animals result in excretion of large numbers of C. burnetii 9 epidemiological knowledge, outbreak investigations, development of diagnostic tools, therapeutic (10 /gram placenta) into the environment. Inhalation of contaminated aerosols from the environment interventions and most importantly for vaccine development. In this chapter, we present an overview are the main risk factor for infection in humans [8,9,13,14]. Following infection, 60% of infected of the current knowledge on C. burnetii biology as well as the approaches used to investigate this humans are usually asymptomatic. In symptomatic patients, the clinical signs of acute infections vary pathogen and identify virulence factors, which is crucial for development of an effective and safe greatly but generally manifest as flu-like illness and pneumonia. Following acute Q fever, a persistent vaccine for long-term control of Q fever. fatigue condition causing significant disabilities in the daily life of the individual is referred to as Q fever fatigue syndrome (QFS). QFS has been described and well documented in many countries Discovery of the Q fever agent following an outbreak, but the cause of development of this condition and proper treatment course are Q fever stands for “Query fever” as very little was known about the causative agent and the disease still unknown [15,16]. Around 1-5% of the clinical cases can result in chronic infections after months when it was first discovered in the 1930s. Q fever was first described in abattoir workers in Brisbane, or years of contracting the disease. This occurs mainly in immune deficient individuals or in Queensland, Australia by Edward Holbrook Derrick [1,2]. Simultaneously, the pathogen was isolated individuals with pre-existing cardiac valvular disease and often leads to life-threatening endocarditis by Frank Macfarlane Burnet and Mavis Freeman from samples sent by Derrick, who hypothesized Q [8,13,17–19]. fever was of rickettsial origin [3]. Around the same time Herald Cox and Gordon Davis at the Rocky Mountain Laboratory in Hamilton, independently isolated a new infectious agent from ticks collected Q fever outbreaks in the Netherlands and source identification at Nine Mile Creek, Montana with rickettsia-like properties [4]. A laboratory worker who became Q fever outbreaks are reported frequently worldwide and have a major public health impact. The accidently infected by this new agent displayed symptoms remarkably similar to the Q fever agent outbreak in the Netherlands during 2007-2010 increased the attention to Q fever as more than 4000 isolated from abattoir workers in Australia, suggesting a common infectious agent. Further cross- human cases were registered. It is by far the largest Q fever outbreak reported in the literature protection studies in mice confirmed these two newly discovered infectious agents to be the same [17,19,20]. The factors leading to the outbreak are not fully understood but have been connected with pathogen [5]. The pathogen was initially designated as Rickettsia burneti, on account of its rickettsia- an increase
Load more

Recommended publications
  • Distribution of Tick-Borne Diseases in China Xian-Bo Wu1, Ren-Hua Na2, Shan-Shan Wei2, Jin-Song Zhu3 and Hong-Juan Peng2*
    Wu et al. Parasites & Vectors 2013, 6:119 http://www.parasitesandvectors.com/content/6/1/119 REVIEW Open Access Distribution of tick-borne diseases in China Xian-Bo Wu1, Ren-Hua Na2, Shan-Shan Wei2, Jin-Song Zhu3 and Hong-Juan Peng2* Abstract As an important contributor to vector-borne diseases in China, in recent years, tick-borne diseases have attracted much attention because of their increasing incidence and consequent significant harm to livestock and human health. The most commonly observed human tick-borne diseases in China include Lyme borreliosis (known as Lyme disease in China), tick-borne encephalitis (known as Forest encephalitis in China), Crimean-Congo hemorrhagic fever (known as Xinjiang hemorrhagic fever in China), Q-fever, tularemia and North-Asia tick-borne spotted fever. In recent years, some emerging tick-borne diseases, such as human monocytic ehrlichiosis, human granulocytic anaplasmosis, and a novel bunyavirus infection, have been reported frequently in China. Other tick-borne diseases that are not as frequently reported in China include Colorado fever, oriental spotted fever and piroplasmosis. Detailed information regarding the history, characteristics, and current epidemic status of these human tick-borne diseases in China will be reviewed in this paper. It is clear that greater efforts in government management and research are required for the prevention, control, diagnosis, and treatment of tick-borne diseases, as well as for the control of ticks, in order to decrease the tick-borne disease burden in China. Keywords: Ticks, Tick-borne diseases, Epidemic, China Review (Table 1) [2,4]. Continuous reports of emerging tick-borne Ticks can carry and transmit viruses, bacteria, rickettsia, disease cases in Shandong, Henan, Hebei, Anhui, and spirochetes, protozoans, Chlamydia, Mycoplasma,Bartonia other provinces demonstrate the rise of these diseases bodies, and nematodes [1,2].
    [Show full text]
  • Melioidosis: an Emerging Infectious Disease
    Review Article www.jpgmonline.com Melioidosis: An emerging infectious disease Raja NS, Ahmed MZ,* Singh NN** Department of Medical ABSTRACT Microbiology, University of Malaya Medical Center, Kuala Lumpur, Infectious diseases account for a third of all the deaths in the developing world. Achievements in understanding Malaysia, *St. the basic microbiology, pathogenesis, host defenses and expanded epidemiology of infectious diseases have Bartholomew’s Hospital, resulted in better management and reduced mortality. However, an emerging infectious disease, melioidosis, West Smithfield, London, is becoming endemic in the tropical regions of the world and is spreading to non-endemic areas. This article UK and **School of highlights the current understanding of melioidosis including advances in diagnosis, treatment and prevention. Biosciences, Cardiff Better understanding of melioidosis is essential, as it is life-threatening and if untreated, patients can succumb University, Cardiff, UK to it. Our sources include a literature review, information from international consensus meetings on melioidosis Correspondence: and ongoing discussions within the medical and scientific community. N. S. Raja, E-mail: [email protected] Received : 21-2-2005 Review completed : 20-3-2005 Accepted : 30-5-2005 PubMed ID : 16006713 KEY WORDS: Melioidosis, Burkholderia pseudomallei, Infection J Postgrad Med 2005;51:140-5 he name melioidosis [also known as Whitmore dis- in returning travellers to Europe from endemic areas.[14] The T ease] is taken from the Greek word ‘melis’ meaning geographic area of the prevalence of the organism is bound to distemper of asses and ‘eidos’ meaning resembles glanders. increase as the awareness increases. Melioidosis is a zoonotic disease caused by Pseudomonas pseudomallei [now known as Burkholderia pseudomallei], a B.
    [Show full text]
  • Coxiella Burnetii
    SENTINEL LEVEL CLINICAL LABORATORY GUIDELINES FOR SUSPECTED AGENTS OF BIOTERRORISM AND EMERGING INFECTIOUS DISEASES Coxiella burnetii American Society for Microbiology (ASM) Revised March 2016 For latest revision, see web site below: https://www.asm.org/Articles/Policy/Laboratory-Response-Network-LRN-Sentinel-Level-C ASM Subject Matter Expert: David Welch, Ph.D. Medical Microbiology Consulting Dallas, TX [email protected] ASM Sentinel Laboratory Protocol Working Group APHL Advisory Committee Vickie Baselski, Ph.D. Barbara Robinson-Dunn, Ph.D. Patricia Blevins, MPH University of Tennessee at Department of Clinical San Antonio Metro Health Memphis Pathology District Laboratory Memphis, TN Beaumont Health System [email protected] [email protected] Royal Oak, MI BRobinson- Erin Bowles David Craft, Ph.D. [email protected] Wisconsin State Laboratory of Penn State Milton S. Hershey Hygiene Medical Center Michael A. Saubolle, Ph.D. [email protected] Hershey, PA Banner Health System [email protected] Phoenix, AZ Christopher Chadwick, MS [email protected] Association of Public Health Peter H. Gilligan, Ph.D. m Laboratories University of North Carolina [email protected] Hospitals/ Susan L. Shiflett Clinical Microbiology and Michigan Department of Mary DeMartino, BS, Immunology Labs Community Health MT(ASCP)SM Chapel Hill, NC Lansing, MI State Hygienic Laboratory at the [email protected] [email protected] University of Iowa [email protected] Larry Gray, Ph.D. Alice Weissfeld, Ph.D. TriHealth Laboratories and Microbiology Specialists Inc. Harvey Holmes, PhD University of Cincinnati College Houston, TX Centers for Disease Control and of Medicine [email protected] Prevention Cincinnati, OH om [email protected] [email protected] David Welch, Ph.D.
    [Show full text]
  • Avoidance of Mechanisms of Innate Immune Response by Neisseria Gonorrhoeae
    ADVANCEMENTS OF MICROBIOLOGY – POSTĘPY MIKROBIOLOGII 2019, 58, 4, 367–373 DOI: 10.21307/PM–2019.58.4.367 AVOIDANCE OF MECHANISMS OF INNATE IMMUNE RESPONSE BY NEISSERIA GONORRHOEAE Jagoda Płaczkiewicz* Department of Virology, Institute of Microbiology, Faculty of Biology, University of Warsaw Submitted in July, accepted in October 2019 Abstract: Neisseria gonorrhoeae (gonococcus) is a Gram-negative bacteria and an etiological agent of the sexually transmitted disease – gonorrhea. N. gonorrhoeae possesses many mechanism to evade the innate immune response of the human host. Most are related to serum resistance and avoidance of complement killing. However the clinical symptoms of gonorrhea are correlated with a significant pres- ence of neutrophils, whose response is also insufficient and modulated by gonococci. 1. Introduction. 2. Adherence ability. 3. Serum resistance and complement system. 4. Neutrophils. 4.1. Phagocytosis. 4.1.1. Oxygen- dependent intracellular killing. 4.1.2. Oxygen-independent intracellular killing. 4.2. Neutrophil extracellular traps. 4.3. Degranulation. 4.4. Apoptosis. 5. Summary UNIKANIE MECHANIZMÓW WRODZONEJ ODPOWIEDZI IMMUNOLOGICZNEJ PRZEZ NEISSERIA GONORRHOEAE Streszczenie: Neisseria gonorrhoeae (gonokok) to Gram-ujemna dwoinka będąca czynnikiem etiologicznym choroby przenoszonej drogą płciową – rzeżączki. N. gonorrhoeae posiada liczne mechanizmy umożliwiające jej unikanie wrodzonej odpowiedzi immunologicznej gospodarza. Większość z nich związana jest ze zdolnością gonokoków do manipulowania układem dopełniacza gospodarza oraz odpor- nością tej bakterii na surowicę. Jednakże symptomy infekcji N. gonorrhoeae wynikają między innymi z obecności licznych neutrofili, których aktywność jest modulowana przez gonokoki. 1. Wprowadzenie. 2. Zdolność adherencji. 3. Surowica i układ dopełniacza. 4. Neutrofile. 4.1. Fagocytoza. 4.1.1. Wewnątrzkomórkowe zabijanie zależne od tlenu. 4.1.2.
    [Show full text]
  • Laboratory Manual for Diagnosis of Sexually Transmitted And
    Department of AIDS Control LaborLaboraattororyy ManualManual fforor DiagnosisDiagnosis ofof SeSexxuallyually TTrransmitansmittteded andand RRepreproductivoductivee TTrractact InInffectionsections FOREWORD Sexually Transmitted Infections (STIs) and Reproductive Tract Infections (RTIs) are diseases of major global concern. About 6% of Indian population is reported to be having STIs. In addition to having high levels of morbidity, they also facilitate transmission of HIV infection. Thus control of STIs goes hand in hand with control of HIV/AIDS. Countrywide strengthening of laboratories by helping them to adopt uniform standardized protocols is very important not only for case detection and treatment, but also to have reliable epidemiological information which will help in evaluation and monitoring of control efforts. It is also essential to have good referral services between primary level of health facilities and higher levels. This manual aims to bring in standard testing practices among laboratories that serve health facilities involved in managing STIs and RTIs. While generic procedures such as staining, microscopy and culture have been dealt with in detail, procedures that employ specific manufacturer defined kits have been left to the laboratories to follow the respective protocols. An introduction to quality system essentials and quality control principles has also been included in the manual to sensitize the readers on the importance of quality assurance and quality management system, which is very much the need of the hour. Manual of Operating Procedures for Diagnosis of STIs/RTIs i PREFACE Sexually Transmitted Infections (STIs) are the most common infectious diseases worldwide, with over 350 million new cases occurring each year, and have far-reaching health, social, and economic consequences.
    [Show full text]
  • The Difference in Clinical Characteristics Between Acute Q Fever and Scrub Typhus in Southern Taiwan
    International Journal of Infectious Diseases (2009) 13, 387—393 http://intl.elsevierhealth.com/journals/ijid The difference in clinical characteristics between acute Q fever and scrub typhus in southern Taiwan Chung-Hsu Lai a,b, Chun-Kai Huang a, Hui-Ching Weng c, Hsing-Chun Chung a, Shiou-Haur Liang a, Jiun-Nong Lin a,b, Chih-Wen Lin d, Chuan-Yuan Hsu d, Hsi-Hsun Lin a,* a Division of Infectious Diseases, Department of Internal Medicine, E-Da Hospital/I-Shou University, 1 E-Da Road, Jiau-Shu Tsuen, Yan-Chau Shiang, Kaohsiung County, 824 Taiwan, Republic of China b Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung County, Taiwan, Republic of China c Department of Health Management, I-Shou University, Kaohsiung County, Taiwan, Republic of China d Section of Gastroenterology, Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung County, Taiwan, Republic of China Received 14 April 2008; received in revised form 17 July 2008; accepted 29 July 2008 Corresponding Editor: Craig Lee, Ottawa, Canada KEYWORDS Summary Acute Q fever; Objective: To identify the differences in clinical characteristics between acute Q fever and scrub Coxiella burnetii; typhus in southern Taiwan. Scrub typhus; Methods: A prospective observational study was conducted in which serological tests for acute Q Orientia tsutsugamushi; fever and scrub typhus were performed simultaneously regardless of which disease was suspected Clinical characteristics; clinically. From April 2004 to December 2007, 80 and 40 cases of serologically confirmed acute Q Taiwan fever and scrub typhus, respectively, were identified and included in the study for comparison.
    [Show full text]
  • Assessment of Coxiella Burnetii Presence After Tick Bite in North‑Eastern Poland
    Infection (2020) 48:85–90 https://doi.org/10.1007/s15010-019-01355-w ORIGINAL PAPER Assessment of Coxiella burnetii presence after tick bite in north‑eastern Poland Karol Borawski1 · Justyna Dunaj1 · Piotr Czupryna1 · Sławomir Pancewicz1 · Renata Świerzbińska1 · Agnieszka Żebrowska2 · Anna Moniuszko‑Malinowska1 Received: 12 June 2019 / Accepted: 4 September 2019 / Published online: 14 September 2019 © The Author(s) 2019 Abstract Purpose The aim of the study is to assess anti-Coxiella burnetii antibodies presence in inhabitants of north-eastern Poland, to assess the risk of Q fever after tick bite and to assess the percentage of co-infection with other pathogens. Methods The serological study included 164 foresters and farmers with a history of tick bite. The molecular study included 540 patients, hospitalized because of various symptoms after tick bite. The control group consisted of 20 honorary blood donors. Anti-Coxiella burnetii antibodies titers were determined by Coxiella burnetii (Q fever) Phase 1 IgG ELISA (DRG International Inc. USA). PCR was performed to detect DNA of C. burnetii, Borrelia burgdorferi and Anaplasma phagocytophilum. Results Anti-C. burnetii IgG was detected in six foresters (7.3%). All foresters with the anti-C. burnetii IgG presence were positive toward anti-B. burgdorferi IgG and anti-TBE (tick-borne encephalitis). Anti-C. burnetii IgG was detected in fve farmers (6%). Four farmers with anti-C. burnetii IgG presence were positive toward anti-B. burgdorferi IgG and two with anti-TBE. Among them one was co-infected with B. burgdorferi and TBEV. Correlations between anti-C. burnetii IgG and anti-B. burgdorferi IgG presence and between anti-C.
    [Show full text]
  • Detection of Tick-Borne Pathogens of the Genera Rickettsia, Anaplasma and Francisella in Ixodes Ricinus Ticks in Pomerania (Poland)
    pathogens Article Detection of Tick-Borne Pathogens of the Genera Rickettsia, Anaplasma and Francisella in Ixodes ricinus Ticks in Pomerania (Poland) Lucyna Kirczuk 1 , Mariusz Piotrowski 2 and Anna Rymaszewska 2,* 1 Department of Hydrobiology, Faculty of Biology, Institute of Biology, University of Szczecin, Felczaka 3c Street, 71-412 Szczecin, Poland; [email protected] 2 Department of Genetics and Genomics, Faculty of Biology, Institute of Biology, University of Szczecin, Felczaka 3c Street, 71-412 Szczecin, Poland; [email protected] * Correspondence: [email protected] Abstract: Tick-borne pathogens are an important medical and veterinary issue worldwide. Environ- mental monitoring in relation to not only climate change but also globalization is currently essential. The present study aimed to detect tick-borne pathogens of the genera Anaplasma, Rickettsia and Francisella in Ixodes ricinus ticks collected from the natural environment, i.e., recreational areas and pastures used for livestock grazing. A total of 1619 specimens of I. ricinus were collected, including ticks of all life stages (adults, nymphs and larvae). The study was performed using the PCR technique. Diagnostic gene fragments msp2 for Anaplasma, gltA for Rickettsia and tul4 for Francisella were ampli- fied. No Francisella spp. DNA was detected in I. ricinus. DNA of A. phagocytophilum was detected in 0.54% of ticks and Rickettsia spp. in 3.69%. Nucleotide sequence analysis revealed that only one species of Rickettsia, R. helvetica, was present in the studied tick population. The present results are a Citation: Kirczuk, L.; Piotrowski, M.; part of a large-scale analysis aimed at monitoring the level of tick infestation in Northwest Poland.
    [Show full text]
  • Antigen Detection Assay for the Diagnosis of Melioidosis
    PI: Title: Antigen Detection assay for the Diagnosis of Melioidosis Received: 12/05/2013 FOA: PA10-124 Council: 05/2014 Competition ID: ADOBE-FORMS-B1 FOA Title: NIAID ADVANCED TECHNOLOGY STTR (NIAID-AT-STTR [R41/R42]) 2 R42 AI102482-03 Dual: Accession Number: 3650491 IPF: 3966401 Organization: INBIOS INTERNATIONAL, INC. Former Number: Department: IRG/SRG: ZRG1 IDM-V (12)B AIDS: N Expedited: N Subtotal Direct Costs Animals: N New Investigator: N (excludes consortium F&A) Humans: Y Early Stage Investigator: N Year 3: Clinical Trial: N Year 4: Current HS Code: E4 Year 5: HESC: N Senior/Key Personnel: Organization: Role Category: Always follow your funding opportunity's instructions for application format. Although this application demonstrates good grantsmanship, time has passed since the grantee applied. The sample may not reflect the latest format or rules. NIAID posts new samples periodically: https://www.niaid.nih.gov/grants-contracts/sample-applications The text of the application is copyrighted. You may use it only for nonprofit educational purposes provided the document remains unchanged and the PI, the grantee organization, and NIAID are credited. Note on Section 508 conformance and accessibility: We have reformatted these samples to improve accessibility for people with disabilities and users of assistive technology. If you have trouble accessing the content, please contact the NIAID Office of Knowledge and Educational Resources at [email protected]. Additions for Review Accepted Publication Accepted manuscript news Post-submission supplemental material. Information about manuscript accepted for publication. OMB Number: 4040-0001 Expiration Date: 06/30/2011 APPLICATION FOR FEDERAL ASSISTANCE 3. DATE RECEIVED BY STATE State Application Identifier SF 424 (R&R) 1.
    [Show full text]
  • Non-Coding Rnas of the Q Fever Agent, Coxiella Burnetii
    University of Montana ScholarWorks at University of Montana Graduate Student Theses, Dissertations, & Professional Papers Graduate School 2015 Non-coding RNAs of the Q fever agent, Coxiella burnetii Indu Ramesh Warrier The University of Montana Follow this and additional works at: https://scholarworks.umt.edu/etd Let us know how access to this document benefits ou.y Recommended Citation Warrier, Indu Ramesh, "Non-coding RNAs of the Q fever agent, Coxiella burnetii" (2015). Graduate Student Theses, Dissertations, & Professional Papers. 4620. https://scholarworks.umt.edu/etd/4620 This Dissertation is brought to you for free and open access by the Graduate School at ScholarWorks at University of Montana. It has been accepted for inclusion in Graduate Student Theses, Dissertations, & Professional Papers by an authorized administrator of ScholarWorks at University of Montana. For more information, please contact [email protected]. NON-CODING RNAS OF THE Q FEVER AGENT, COXIELLA BURNETII By INDU RAMESH WARRIER M.Sc (Med), Kasturba Medical College, Manipal, India, 2010 Dissertation presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy Cellular, Molecular and Microbial Biology The University of Montana Missoula, MT August, 2015 Approved by: Sandy Ross, Dean of The Graduate School Graduate School Michael F. Minnick, Chair Division of Biological Sciences Stephen J. Lodmell Division of Biological Sciences Scott D. Samuels Division of Biological Sciences Scott Miller Division of Biological Sciences Keith Parker Department of Biomedical and Pharmaceutical Sciences Warrier, Indu, PhD, Summer 2015 Cellular, Molecular and Microbial Biology Non-coding RNAs of the Q fever agent, Coxiella burnetii Chairperson: Michael F. Minnick Coxiella burnetii is an obligate intracellular bacterial pathogen that undergoes a biphasic developmental cycle, alternating between a small cell variant (SCV) and a large cell variant (LCV).
    [Show full text]
  • Francisella Tularensis Subspecies Holarctica and Tularemia in Germany
    microorganisms Review Francisella tularensis Subspecies holarctica and Tularemia in Germany 1, 2, 3 1 1 Sandra Appelt y, Mirko Faber y , Kristin Köppen , Daniela Jacob , Roland Grunow and Klaus Heuner 3,* 1 Centre for Biological Threats and Special Pathogens (ZBS 2), Robert Koch Institute, 13353 Berlin, Germany; [email protected] (S.A.); [email protected] (D.J.); [email protected] (R.G.) 2 Gastrointestinal Infections, Zoonoses and Tropical Infections (Division 35), Department for Infectious Disease Epidemiology, Robert Koch Institute, 13353 Berlin, Germany; [email protected] 3 Cellular Interactions of Bacterial Pathogens, ZBS 2, Robert Koch Institute, 13353 Berlin, Germany; [email protected] * Correspondence: [email protected]; Tel.: +49-301-8754-2226 These authors contributed equally to this work. y Received: 27 August 2020; Accepted: 18 September 2020; Published: 22 September 2020 Abstract: Tularemia is a zoonotic disease caused by Francisella tularensis a small, pleomorphic, facultative intracellular bacterium. In Europe, infections in animals and humans are caused mainly by Francisella tularensis subspecies holarctica. Humans can be exposed to the pathogen directly and indirectly through contact with sick animals, carcasses, mosquitoes and ticks, environmental sources such as contaminated water or soil, and food. So far, F. tularensis subsp. holarctica is the only Francisella species known to cause tularemia in Germany. On the basis of surveillance data, outbreak investigations, and literature, we review herein the epidemiological situation—noteworthy clinical cases next to genetic diversity of F. tularensis subsp. holarctica strains isolated from patients. In the last 15 years, the yearly number of notified cases of tularemia has increased steadily in Germany, suggesting that the disease is re-emerging.
    [Show full text]
  • Pathogenic Bacteria and Clinical Significance Raphael Eisenhofer Inje University College of Medicine, Korea
    Journal of Microbiology and Immunology AbstractEditoial Pathogenic bacteria and clinical significance Raphael Eisenhofer Inje University College of Medicine, Korea Pathogenic bacteria are bacteria that can cause disease. cystic fibrosis. Examples of these opportunistic pathogens This article deals with human pathogenic bacteria. Al- include Pseudomonas aeruginosa, Burkholderia cenoce- though most bacteria are harmless or often beneficial, pacia, and Mycobacterium avium. Intracellular: Obligate some are pathogenic, with the number of species esti- intracellular parasites (e.g. Chlamydophila, Ehrlichia, mated as fewer than a hundred that are seen to cause Rickettsia) have the ability to only grow and replicate in- infectious diseases in humans. By contrast, several thou- side other cells. Even these intracellular infections may sand species exist in the human digestive system. One of be asymptomatic, requiring an incubation period. An ex- the bacterial diseases with the highest disease burden is ample of this is Rickettsia which causes typhus. Another tuberculosis, caused by Mycobacterium tuberculosis bac- causes Rocky Mountain spotted fever. Chlamydia is a phy- teria, which kills about 2 million people a year, mostly lum of intracellular parasites. These pathogens can cause in sub-Saharan Africa. Pathogenic bacteria contribute to pneumonia or urinary tract infection and may be involved other globally important diseases, such as pneumonia, in coronary heart disease. Other groups of intracellular which can be caused by bacteria such as Streptococcus bacterial pathogens include Salmonella, Neisseria, Brucel- and Pseudomonas, and foodborne illnesses, which can la, Mycobacterium, Nocardia, Listeria, Francisella, Legio- be caused by bacteria such as Shigella, Campylobacter, nella, and Yersinia pestis. These can exist intracellularly, and Salmonella.
    [Show full text]