DOCSLIB.ORG

A Genomics-Based Approach to Biodefence Preparedness

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Genomics-Based Approach to Biodefence Preparedness REVIEWS A GENOMICS-BASED APPROACH TO BIODEFENCE PREPAREDNESS Claire M. Fraser The anthrax letter attacks in October 2001, followed by the SARS outbreak in early 2003, dramatically illustrated our vulnerability to both deliberate and natural outbreaks of infectious disease. The availability of pathogen genome sequences and high-throughput methods for studying the biology of both pathogens and their hosts have provided new insights into the mechanisms of pathogenesis and host defence. As infectious disease research expands to include major bioterror agents, genomics-based approaches will provide one of the cornerstones of efforts to develop more accurate diagnostics, new therapeutics and vaccines, and further capabilities for microbial forensics. CATEGORY A AGENTS Since the anthrax letter attacks in October 2001, the US bioterror agents; develop new vaccines, antimicrobial Organisms that pose a risk to federal government has placed a premium on homeland and antiviral therapeutics, and diagnostic tools against national security because they: security, with research and development considered to the most threatening diseases, such as smallpox, anthrax, can be easily transmitted from be a key component of an integrated and unified biode- and plague; and to develop research resources such as person to person; result in high mortality rates and have the fence strategy. For fiscal year 2003, President Bush pro- BSL3 and BSL4 LABORATORY containment facilities to allow potential for major public health posed a $1.75 billion budget for biodefence research, to more work on category A–C agents than is possible at impact; might cause public be administered primarily through the National present. Ultimately, the expectation is that these new panic and social disruption; and Institutes of Allergy and Infectious Diseases (NIAID) at research activities will increase our level of prepared- require special action for public the National Institutes of Health (NIH). As summarized ness so that we might better respond to, and protect the health preparedness. on the NIAID web site (see online links box), the pro- world’s population against, bioterrorism. CATEGORY B AGENTS posed new biodefence research agenda will broadly Much needs to be done to realize the ambitious goals Organisms that are moderately focus on studies of CATEGORY A, CATEGORY B and CATEGORY C of the NIAID Strategic Plan for Biodefense Research — easy to disseminate, result in BIOTERROR AGENTS (for more information, see online links this includes not only an expanded research portfolio moderate morbidity rates and low mortality rates. They require box). These potential bioterror agents share several fea- and the development of new tools and reagents, but also specific enhancements of the tures, including a high morbidity or mortality that is the creation of new research facilities and the recruit- Center for Disease Control and associated with infection, a high likelihood of person- ment of new investigators into the area of infectious dis- Prevention’s diagnostic capacity to-person spread, the ability to be made into a weapon ease research. On 4 September 2003, the US Department and enhanced disease and spread by aerosols or food and water supplies, and of Health and Human Services announced the creation surveillance. the potential to cause widespread panic in the public if of eight Regional Centers of Excellence for Biodefense released into the environment. The goals of this acceler- and Emerging Diseases (RCEs). The aim of the RCEs is ated research and development agenda are to: understand to bring together investigators from several disciplines better the molecular mechanisms that are responsible for and public and private institutions to tackle the most pathogen transmission, virulence and invasion; develop compelling research questions that are relevant to The Institute for Genomic new animal models of disease that can be used in the bioterror agents, particularly anthrax and smallpox, in Research, 9712 Medical study of potential bioterror agents; elucidate host large, comprehensive programmes (for more informa- Center Drive, Rockville, Maryland 20850, USA. responses to microbes to understand better the complex tion on RCEs, see online links box). Collectively, what e-mail: [email protected] parameters of innate and acquired immunity, and how sets this new research agenda apart from previous doi:10.1038/nrg1245 they might be manipulated after exposure to potential efforts on the study of infectious disease agents is the NATURE REVIEWS | GENETICS VOLUME 5 | JANUARY 2004 | 23 REVIEWS expectation that in a relatively short period of time information derived would be available to all scientists these expanded research activities must achieve several for all time. We could then think about a new post- key objectives that can provide immediate benefits in genomic era of microbe biology.” (REF.1).As genomics, the public health arena. It is also anticipated that one of proteomics and bioinformatics are considered to be key the other positive spin-offs of the new bioterrorism enabling technologies in the development of new meth- research agenda will most certainly be a better under- ods to deal with potential bioterror agents and emerging standing of other more common and naturally occur- infectious diseases, this review summarizes the status of ring infectious agents. This is an important goal because pathogen genome sequencing and analysis at present we are at least as vulnerable to emerging infectious dis- and discusses how these approaches might best be eases as we are to deliberate attacks. The recent severe applied to biodefence preparedness. acute respiratory syndrome (SARS) epidemic that in 9 months killed over 900 people in 31 countries illus- Vulnerabilities and assessment of needs trates just how devastating a new disease can be, and The intentional spread of disease during war (biowar- how quickly it can spread around the world (for more fare) has a long history that dates back to the ancient information on SARS, see online links box). Greeks and Romans (BOX 1).Bioterrorism, by contrast, Barry Bloom, the present Director of the Harvard has a much shorter history. Recent events, in particular School of Public Health, summarized the potential of the anthrax letter attacks of 2001, have exposed our vul- genomics-based approaches to expand our understand- nerabilities in the area of BIOPREPAREDNESS against both ing of the biology of pathogens in 1995 (REF.1) after the natural and deliberate outbreaks of infectious disease. publication of the second complete microbial genome As there is a dearth of investigators who study biowar- sequence. He stated that “The power and cost effective- fare pathogens and only a few specialized facilities for ness of modern genome sequencing technology mean carrying out such research, we only have a rudimentary CATEGORY C AGENTS These third highest priority that complete genome sequences of 25 of the major understanding of the mechanisms of pathogenesis for agents include emerging bacterial and parasitic pathogens could be available most of these agents. We also lack rapid and precise pathogens that could be within 5 years. For about $100 million we could buy the diagnostic assays for identifying most of these species. engineered for mass sequence of every virulence determinant, every protein The deliberate release of microbial pathogens can be dissemination in the future antigen, and every drug target. It would represent for done, for the most part, without being noticed, until sig- because of their availability, ease of production and each pathogen a one-time investment from which the nificant numbers of symptomatic patients appear at dissemination, and their potential for high morbidity and mortality rates and major health Box 1 | History of biowarfare and bioterrorism impact. Biological warfare began with the ancient Greeks and Romans, who used toxic plants and human and animal corpses to BSL3 LABORATORY poison drinking-water wells. More recently (in the fourteenth century) the Tartars catapulted bodies of plague victims Laboratory facilities for work on over the city walls to infect the Genoese inhabitants of Caffa, a trade centre on the Black Sea. The Genoese took to their biological agents that might boats to escape, spreading the Black Death along shipping routes throughout Europe. In just a few years the plague killed cause serious or potentially lethal disease as a result of approximately one-third of Europe’s population. exposure by the inhalation The seventeenth and eighteenth centuries saw French and British soldiers intentionally infect native Americans with route. European diseases. For example, Sir Jeffrey Amherst ordered that smallpox be spread as a way “…to inoculate the Indians by means of blankets … to extirpate this execrable race…”63. BSL4 LABORATORY During the First World War, Germany had plans to conduct covert operations in the United States with the intent to Laboratory facilities for work infect horses and cattle that were destined for service in Europe with GLANDERS and anthrax. During the Second World with dangerous and exotic biological agents that pose War, bioweapons programmes were initiated in every major participating country. The Japanese military practiced a high individual risk of biowarfare on a large scale against the Chinese in Manchuria during the 1940s, infecting the population with various aerosol-transmitted laboratory disease agents including anthrax, cholera and plague. The Cold War brought about
Load more

Recommended publications
  • Reporting of Diseases and Conditions Regulation, Amendment, M.R. 289/2014
    THE PUBLIC HEALTH ACT LOI SUR LA SANTÉ PUBLIQUE (C.C.S.M. c. P210) (c. P210 de la C.P.L.M.) Reporting of Diseases and Conditions Règlement modifiant le Règlement sur la Regulation, amendment déclaration de maladies et d'affections Regulation 289/2014 Règlement 289/2014 Registered December 23, 2014 Date d'enregistrement : le 23 décembre 2014 Manitoba Regulation 37/2009 amended Modification du R.M. 37/2009 1 The Reporting of Diseases and 1 Le présent règlement modifie le Conditions Regulation , Manitoba Règlement sur la déclaration de maladies et Regulation 37/2009, is amended by this d'affections , R.M. 37/2009. regulation. 2 Schedules A and B are replaced with 2 Les annexes A et B sont remplacées Schedules A and B to this regulation. par les annexes A et B du présent règlement. Coming into force Entrée en vigueur 3 This regulation comes into force on 3 Le présent règlement entre en vigueur January 1, 2015, or on the day it is registered le 1 er janvier 2015 ou à la date de son under The Statutes and Regulations Act , enregistrement en vertu de Loi sur les textes whichever is later. législatifs et réglementaires , si cette date est postérieure. December 19, 2014 Minister of Health/La ministre de la Santé, 19 décembre 2014 Sharon Blady 1 SCHEDULE A (Section 1) 1 The following diseases are diseases requiring contact notification in accordance with the disease-specific protocol. Common name Scientific or technical name of disease or its infectious agent Chancroid Haemophilus ducreyi Chlamydia Chlamydia trachomatis (including Lymphogranuloma venereum (LGV) serovars) Gonorrhea Neisseria gonorrhoeae HIV Human immunodeficiency virus Syphilis Treponema pallidum subspecies pallidum Tuberculosis Mycobacterium tuberculosis Mycobacterium africanum Mycobacterium canetti Mycobacterium caprae Mycobacterium microti Mycobacterium pinnipedii Mycobacterium bovis (excluding M.
    [Show full text]
  • Characterization of the Interaction Between R. Conorii and Human
    Louisiana State University LSU Digital Commons LSU Doctoral Dissertations Graduate School 4-5-2018 Characterization of the Interaction Between R. Conorii and Human Host Vitronectin in Rickettsial Pathogenesis Abigail Inez Fish Louisiana State University and Agricultural and Mechanical College, [email protected] Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_dissertations Part of the Bacteria Commons, Bacteriology Commons, Biology Commons, Immunology of Infectious Disease Commons, and the Pathogenic Microbiology Commons Recommended Citation Fish, Abigail Inez, "Characterization of the Interaction Between R. Conorii and Human Host Vitronectin in Rickettsial Pathogenesis" (2018). LSU Doctoral Dissertations. 4566. https://digitalcommons.lsu.edu/gradschool_dissertations/4566 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Doctoral Dissertations by an authorized graduate school editor of LSU Digital Commons. For more information, please [email protected]. CHARACTERIZATION OF THE INTERACTION BETWEEN R. CONORII AND HUMAN HOST VITRONECTIN IN RICKETTSIAL PATHOGENESIS A Dissertation Submitted to the Graduate Faculty of the Louisiana State University and Agricultural and Mechanical College in partial fulfillment of the requirements for the degree of Doctor of Philosophy in The Interdepartmental Program in Biomedical and Veterinary Medical Sciences Through the Department of Pathobiological Sciences by Abigail Inez
    [Show full text]
  • BD-CS-057, REV 0 | AUGUST 2017 | Page 1
    EXPLIFY RESPIRATORY PATHOGENS BY NEXT GENERATION SEQUENCING Limitations Negative results do not rule out viral, bacterial, or fungal infections. Targeted, PCR-based tests are generally more sensitive and are preferred when specific pathogens are suspected, especially for DNA viruses (Adenovirus, CMV, HHV6, HSV, and VZV), mycobacteria, and fungi. The analytical sensitivity of this test depends on the cellularity of the sample and the concentration of all microbes present. Analytical sensitivity is assessed using Internal Controls that are added to each sample. Sequencing data for Internal Controls is quantified. Samples with Internal Control values below the validated minimum may have reduced analytical sensitivity or contain inhibitors and are reported as ‘Reduced Analytical Sensitivity’. Additional respiratory pathogens to those reported cannot be excluded in samples with ‘Reduced Analytical Sensitivity’. Due to the complexity of next generation sequencing methodologies, there may be a risk of false-positive results. Contamination with organisms from the upper respiratory tract during specimen collection can also occur. The detection of viral, bacterial, and fungal nucleic acid does not imply organisms causing invasive infection. Results from this test need to be interpreted in conjunction with the clinical history, results of other laboratory tests, epidemiologic information, and other available data. Confirmation of positive results by an alternate method may be indicated in select cases. Validated Organisms BACTERIA Achromobacter
    [Show full text]
  • Phenotypic and Genomic Analyses of Burkholderia Stabilis Clinical Contamination, Switzerland Helena M.B
    RESEARCH Phenotypic and Genomic Analyses of Burkholderia stabilis Clinical Contamination, Switzerland Helena M.B. Seth-Smith, Carlo Casanova, Rami Sommerstein, Dominik M. Meinel,1 Mohamed M.H. Abdelbary,2 Dominique S. Blanc, Sara Droz, Urs Führer, Reto Lienhard, Claudia Lang, Olivier Dubuis, Matthias Schlegel, Andreas Widmer, Peter M. Keller,3 Jonas Marschall, Adrian Egli A recent hospital outbreak related to premoistened gloves pathogens that generally fall within the B. cepacia com- used to wash patients exposed the difficulties of defining plex (Bcc) (1). Burkholderia bacteria have large, flexible, Burkholderia species in clinical settings. The outbreak strain multi-replicon genomes, a large metabolic repertoire, vari- displayed key B. stabilis phenotypes, including the inabil- ous virulence factors, and inherent resistance to many anti- ity to grow at 42°C; we used whole-genome sequencing to microbial drugs (2,3). confirm the pathogen was B. stabilis. The outbreak strain An outbreak of B. stabilis was identified among hos- genome comprises 3 chromosomes and a plasmid, shar- ing an average nucleotide identity of 98.4% with B. stabilis pitalized patients across several cantons in Switzerland ATCC27515 BAA-67, but with 13% novel coding sequenc- during 2015–2016 (4). The bacterium caused bloodstream es. The genome lacks identifiable virulence factors and has infections, noninvasive infections, and wound contamina- no apparent increase in encoded antimicrobial drug resis- tions. The source of the infection was traced to contaminat- tance, few insertion sequences, and few pseudogenes, ed commercially available, premoistened washing gloves suggesting this outbreak was an opportunistic infection by used for bedridden patients. After hospitals discontinued an environmental strain not adapted to human pathogenic- use of these gloves, the outbreak resolved.
    [Show full text]
  • “Candidatus Deianiraea Vastatrix” with the Ciliate Paramecium Suggests
    bioRxiv preprint doi: https://doi.org/10.1101/479196; this version posted November 27, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. The extracellular association of the bacterium “Candidatus Deianiraea vastatrix” with the ciliate Paramecium suggests an alternative scenario for the evolution of Rickettsiales 5 Castelli M.1, Sabaneyeva E.2, Lanzoni O.3, Lebedeva N.4, Floriano A.M.5, Gaiarsa S.5,6, Benken K.7, Modeo L. 3, Bandi C.1, Potekhin A.8, Sassera D.5*, Petroni G.3* 1. Centro Romeo ed Enrica Invernizzi Ricerca Pediatrica, Dipartimento di Bioscienze, Università 10 degli studi di Milano, Milan, Italy 2. Department of Cytology and Histology, Faculty of Biology, Saint Petersburg State University, Saint-Petersburg, Russia 3. Dipartimento di Biologia, Università di Pisa, Pisa, Italy 4 Centre of Core Facilities “Culture Collections of Microorganisms”, Saint Petersburg State 15 University, Saint Petersburg, Russia 5. Dipartimento di Biologia e Biotecnologie, Università degli studi di Pavia, Pavia, Italy 6. UOC Microbiologia e Virologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 7. Core Facility Center for Microscopy and Microanalysis, Saint Petersburg State University, Saint- Petersburg, Russia 20 8. Department of Microbiology, Faculty of Biology, Saint Petersburg State University, Saint- Petersburg, Russia * Corresponding authors, contacts: [email protected] ; [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/479196; this version posted November 27, 2018.
    [Show full text]
  • Reportable Disease Surveillance in Virginia, 2013
    Reportable Disease Surveillance in Virginia, 2013 Marissa J. Levine, MD, MPH State Health Commissioner Report Production Team: Division of Surveillance and Investigation, Division of Disease Prevention, Division of Environmental Epidemiology, and Division of Immunization Virginia Department of Health Post Office Box 2448 Richmond, Virginia 23218 www.vdh.virginia.gov ACKNOWLEDGEMENT In addition to the employees of the work units listed below, the Office of Epidemiology would like to acknowledge the contributions of all those engaged in disease surveillance and control activities across the state throughout the year. We appreciate the commitment to public health of all epidemiology staff in local and district health departments and the Regional and Central Offices, as well as the conscientious work of nurses, environmental health specialists, infection preventionists, physicians, laboratory staff, and administrators. These persons report or manage disease surveillance data on an ongoing basis and diligently strive to control morbidity in Virginia. This report would not be possible without the efforts of all those who collect and follow up on morbidity reports. Divisions in the Virginia Department of Health Office of Epidemiology Disease Prevention Telephone: 804-864-7964 Environmental Epidemiology Telephone: 804-864-8182 Immunization Telephone: 804-864-8055 Surveillance and Investigation Telephone: 804-864-8141 TABLE OF CONTENTS INTRODUCTION Introduction ......................................................................................................................................1
    [Show full text]
  • Mechanisms of Rickettsia Parkeri Invasion of Host Cells and Early Actin-Based Motility
    Mechanisms of Rickettsia parkeri invasion of host cells and early actin-based motility By Shawna Reed A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Microbiology in the Graduate Division of the University of California, Berkeley Committee in charge: Professor Matthew D. Welch, Chair Professor David G. Drubin Professor Daniel Portnoy Professor Kathleen R. Ryan Fall 2012 Mechanisms of Rickettsia parkeri invasion of host cells and early actin-based motility © 2012 By Shawna Reed ABSTRACT Mechanisms of Rickettsia parkeri invasion of host cells and early actin-based motility by Shawna Reed Doctor of Philosophy in Microbiology University of California, Berkeley Professor Matthew D. Welch, Chair Rickettsiae are obligate intracellular pathogens that are transmitted to humans by arthropod vectors and cause diseases such as spotted fever and typhus. Spotted fever group (SFG) Rickettsia hijack the host actin cytoskeleton to invade, move within, and spread between eukaryotic host cells during their obligate intracellular life cycle. Rickettsia express two bacterial proteins that can activate actin polymerization: RickA activates the host actin-nucleating Arp2/3 complex while Sca2 directly nucleates actin filaments. In this thesis, I aimed to resolve which host proteins were required for invasion and intracellular motility, and to determine how the bacterial proteins RickA and Sca2 contribute to these processes. Although rickettsiae require the host cell actin cytoskeleton for invasion, the cytoskeletal proteins that mediate this process have not been completely described. To identify the host factors important during cell invasion by Rickettsia parkeri, a member of the SFG, I performed an RNAi screen targeting 105 proteins in Drosophila melanogaster S2R+ cells.
    [Show full text]
  • Gene Gain and Loss Events in Rickettsia and Orientia Species Kalliopi Georgiades1,2, Vicky Merhej1, Khalid El Karkouri1, Didier Raoult1, Pierre Pontarotti2*
    Georgiades et al. Biology Direct 2011, 6:6 http://www.biology-direct.com/content/6/1/6 RESEARCH Open Access Gene gain and loss events in Rickettsia and Orientia species Kalliopi Georgiades1,2, Vicky Merhej1, Khalid El Karkouri1, Didier Raoult1, Pierre Pontarotti2* Abstract Background: Genome degradation is an ongoing process in all members of the Rickettsiales order, which makes these bacterial species an excellent model for studying reductive evolution through interspecies variation in genome size and gene content. In this study, we evaluated the degree to which gene loss shaped the content of some Rickettsiales genomes. We shed light on the role played by horizontal gene transfers in the genome evolution of Rickettsiales. Results: Our phylogenomic tree, based on whole-genome content, presented a topology distinct from that of the whole core gene concatenated phylogenetic tree, suggesting that the gene repertoires involved have different evolutionary histories. Indeed, we present evidence for 3 possible horizontal gene transfer events from various organisms to Orientia and 6 to Rickettsia spp., while we also identified 3 possible horizontal gene transfer events from Rickettsia and Orientia to other bacteria. We found 17 putative genes in Rickettsia spp. that are probably the result of de novo gene creation; 2 of these genes appear to be functional. On the basis of these results, we were able to reconstruct the gene repertoires of “proto-Rickettsiales” and “proto-Rickettsiaceae”, which correspond to the ancestors of Rickettsiales and Rickettsiaceae, respectively. Finally, we found that 2,135 genes were lost during the evolution of the Rickettsiaceae to an intracellular lifestyle. Conclusions: Our phylogenetic analysis allowed us to track the gene gain and loss events occurring in bacterial genomes during their evolution from a free-living to an intracellular lifestyle.
    [Show full text]
  • Rickettsial Infections and Their Clinical Presentations in the Western Province of Sri Lanka: a Hospital-Based Study§
    International Journal of Infectious Diseases (2008) 12, 198—202 http://intl.elsevierhealth.com/journals/ijid Rickettsial infections and their clinical presentations in the Western Province of Sri Lanka: a hospital-based study§ R. Premaratna a,*, A.D. Loftis b, T.G.A.N. Chandrasena c, G.A. Dasch b, H.J. de Silva a a Department of Medicine, Faculty of Medicine, University of Kelaniya, PO Box 6, Thalagolla Rd, Ragama, Sri Lanka b Viral and Rickettsial Zoonoses Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA c Department of Parasitology, Faculty of Medicine, University of Kelaniya, Sri Lanka Received 18 September 2006; received in revised form 21 February 2007; accepted 18 June 2007 Corresponding Editor: Craig Lee, Ottawa, Canada KEYWORDS Summary Scrub typhus; Background: Rickettsial infections are re-emerging. A study of the geographical distribution of Spotted fever group rickettsial infections, their clinical manifestations, and their complications would facilitate early rickettsioses; diagnosis. Sri Lanka Methods: Thirty-one selected patients from the Western Province of Sri Lanka were studied for rickettsial species, clinical manifestations, and complications. Results: Of 31 patients with possible rickettsioses, 29 (94%) fell into the categories of confirmed, presumptive, or exposed cases of acute rickettsial infections (scrub typhus was diagnosed in 19 (66%), spotted fever group in eight (28%)). Early acute infection or past exposure was suggested in two (7%) cases; cross-reactivity of antigens or past exposure to one or more species was suggested in nine (31%). Seventeen out of 19 (89%) patients with scrub typhus had eschars. Nine out of 29 (32%) patients had a discrete erythematous papular rash: seven caused by spotted fever group, two by scrub typhus.
    [Show full text]
  • Insights Into the Pathogenicity of Burkholderia Pseudomallei
    REVIEWS Melioidosis: insights into the pathogenicity of Burkholderia pseudomallei W. Joost Wiersinga*, Tom van der Poll*, Nicholas J. White‡§, Nicholas P. Day‡§ and Sharon J. Peacock‡§ Abstract | Burkholderia pseudomallei is a potential bioterror agent and the causative agent of melioidosis, a severe disease that is endemic in areas of Southeast Asia and Northern Australia. Infection is often associated with bacterial dissemination to distant sites, and there are many possible disease manifestations, with melioidosis septic shock being the most severe. Eradication of the organism following infection is difficult, with a slow fever-clearance time, the need for prolonged antibiotic therapy and a high rate of relapse if therapy is not completed. Mortality from melioidosis septic shock remains high despite appropriate antimicrobial therapy. Prevention of disease and a reduction in mortality and the rate of relapse are priority areas for future research efforts. Studying how the disease is acquired and the host–pathogen interactions involved will underpin these efforts; this review presents an overview of current knowledge in these areas, highlighting key topics for evaluation. Melioidosis is a serious disease caused by the aerobic, rifamycins, colistin and aminoglycosides), but is usually Gram-negative soil-dwelling bacillus Burkholderia pseu- susceptible to amoxicillin-clavulanate, chloramphenicol, domallei and is most common in Southeast Asia and doxycycline, trimethoprim-sulphamethoxazole, ureido- Northern Australia. Melioidosis is responsible for 20% of penicillins, ceftazidime and carbapenems2,4. Treatment all community-acquired septicaemias and 40% of sepsis- is required for 20 weeks and is divided into intravenous related mortality in northeast Thailand. Reported cases are and oral phases2,4. Initial intravenous therapy is given likely to represent ‘the tip of the iceberg’1,2, as confirmation for 10–14 days; ceftazidime or a carbapenem are the of disease depends on bacterial isolation, a technique that drugs of choice.
    [Show full text]
  • Antimicrobial Susceptibilities of Selected Pathogens, 1999
    ✔ Antimicrobial Susceptibilities * * † 7 of Selected Pathogens, 1999 8 e † a 2 ✔ ✔ † 3 ✔ † 4 5 6 culosis * r 1 urium spp. m L spp. Sampling Methodology 2 L † all isolates tested * ~ 20% sample of statewide isolates received at MDH spp. ~10% sample of statewide isolates received at MDH Salmonella ** all isolates tested from 7-county metropolitan area oup A streptococci ✔ oup B streptococci r isolates from a normally sterile site r Other (non-typhoidal) G Campylobacter Salmonella typhi Shigella Neisseria gonorrhoeae Neisseria meningitidis G Streptococcus pneumoni Mycobacterium tube No. of Isolates Tested 131 160 43 20 250 55 162 192 559 163 123456 123456% Susceptib123456le 123456123456 123456 123451623456 123451623456 ampicillin 1234561234566012345686 123456 15123456123456 100 100 123456123456 123451623451623451623451623456 123456 penicillin 123456123456123456123456123456 98100 100 76 123456 123456123456123456123456123456123456123456123456 123456 123451623451623451623456 123451623451623456 123456 cefuroxime sodium 123456123456123456123456 100123456123456123456 81 123456 123456123456123456123456123456123456123456123456 123456 cefotaxime 123451623451623451623451623456 100 100100 83 123456 123456123456123456123456123456 123456123456123456123456 123456 123456123456123456123456 ceftriaxone 123456 100 95 100 100 100 123451623451623451623456 -lactam antibiotics 123456123456123456123456123456 123456123456123456123456 β 123451623451623451623451623456 123451623456 123456 meropenem 123456123456123456123456123456 100 123456123456 83 123456 123456123456123456123456123456123456123456123456
    [Show full text]
  • Microbial NAD Metabolism: Lessons from Comparative Genomics
    Dartmouth College Dartmouth Digital Commons Dartmouth Scholarship Faculty Work 9-2009 Microbial NAD Metabolism: Lessons from Comparative Genomics Francesca Gazzaniga Rebecca Stebbins Sheila Z. Chang Mark A. McPeek Dartmouth College Charles Brenner Carver College of Medicine Follow this and additional works at: https://digitalcommons.dartmouth.edu/facoa Part of the Biochemistry Commons, Genetics and Genomics Commons, Medicine and Health Sciences Commons, and the Microbiology Commons Dartmouth Digital Commons Citation Gazzaniga, Francesca; Stebbins, Rebecca; Chang, Sheila Z.; McPeek, Mark A.; and Brenner, Charles, "Microbial NAD Metabolism: Lessons from Comparative Genomics" (2009). Dartmouth Scholarship. 1191. https://digitalcommons.dartmouth.edu/facoa/1191 This Article is brought to you for free and open access by the Faculty Work at Dartmouth Digital Commons. It has been accepted for inclusion in Dartmouth Scholarship by an authorized administrator of Dartmouth Digital Commons. For more information, please contact [email protected]. MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, Sept. 2009, p. 529–541 Vol. 73, No. 3 1092-2172/09/$08.00ϩ0 doi:10.1128/MMBR.00042-08 Copyright © 2009, American Society for Microbiology. All Rights Reserved. Microbial NAD Metabolism: Lessons from Comparative Genomics Francesca Gazzaniga,1,2 Rebecca Stebbins,1,2 Sheila Z. Chang,1,2 Mark A. McPeek,2 and Charles Brenner1,3* Departments of Genetics and Biochemistry and Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire
    [Show full text]