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      The Past and Future of Tuberculosis Research

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      Publication date (Electronic):
      Journal: PLoS Pathogens
      Publisher: Public Library of Science

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          Abstract

          Renewed efforts in tuberculosis (TB) research have led to important new insights into the biology and epidemiology of this devastating disease. Yet, in the face of the modern epidemics of HIV/AIDS, diabetes, and multidrug resistance—all of which contribute to susceptibility to TB—global control of the disease will remain a formidable challenge for years to come. New high-throughput genomics technologies are already contributing to studies of TB's epidemiology, comparative genomics, evolution, and host–pathogen interaction. We argue here, however, that new multidisciplinary approaches—especially the integration of epidemiology with systems biology in what we call “systems epidemiology”—will be required to eliminate TB.

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          Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms.

          M. C. J. Maiden, J. Bygraves, E Feil … (1998)
          Traditional and molecular typing schemes for the characterization of pathogenic microorganisms are poorly portable because they index variation that is difficult to compare among laboratories. To overcome these problems, we propose multilocus sequence typing (MLST), which exploits the unambiguous nature and electronic portability of nucleotide sequence data for the characterization of microorganisms. To evaluate MLST, we determined the sequences of approximately 470-bp fragments from 11 housekeeping genes in a reference set of 107 isolates of Neisseria meningitidis from invasive disease and healthy carriers. For each locus, alleles were assigned arbitrary numbers and dendrograms were constructed from the pairwise differences in multilocus allelic profiles by cluster analysis. The strain associations obtained were consistent with clonal groupings previously determined by multilocus enzyme electrophoresis. A subset of six gene fragments was chosen that retained the resolution and congruence achieved by using all 11 loci. Most isolates from hyper-virulent lineages of serogroups A, B, and C meningococci were identical for all loci or differed from the majority type at only a single locus. MLST using six loci therefore reliably identified the major meningococcal lineages associated with invasive disease. MLST can be applied to almost all bacterial species and other haploid organisms, including those that are difficult to cultivate. The overwhelming advantage of MLST over other molecular typing methods is that sequence data are truly portable between laboratories, permitting one expanding global database per species to be placed on a World-Wide Web site, thus enabling exchange of molecular typing data for global epidemiology via the Internet.
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            The genetic structure and history of Africans and African Americans.

            S. A. Tishkoff, F. A. Reed, F. R. Friedlaender … (2009)
            Africa is the source of all modern humans, but characterization of genetic variation and of relationships among populations across the continent has been enigmatic. We studied 121 African populations, four African American populations, and 60 non-African populations for patterns of variation at 1327 nuclear microsatellite and insertion/deletion markers. We identified 14 ancestral population clusters in Africa that correlate with self-described ethnicity and shared cultural and/or linguistic properties. We observed high levels of mixed ancestry in most populations, reflecting historical migration events across the continent. Our data also provide evidence for shared ancestry among geographically diverse hunter-gatherer populations (Khoesan speakers and Pygmies). The ancestry of African Americans is predominantly from Niger-Kordofanian (approximately 71%), European (approximately 13%), and other African (approximately 8%) populations, although admixture levels varied considerably among individuals. This study helps tease apart the complex evolutionary history of Africans and African Americans, aiding both anthropological and genetic epidemiologic studies.
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              Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.

              Troy Querec, Rama Akondy, Eva K. Lee … (2009)
              A major challenge in vaccinology is to prospectively determine vaccine efficacy. Here we have used a systems biology approach to identify early gene 'signatures' that predicted immune responses in humans vaccinated with yellow fever vaccine YF-17D. Vaccination induced genes that regulate virus innate sensing and type I interferon production. Computational analyses identified a gene signature, including complement protein C1qB and eukaryotic translation initiation factor 2 alpha kinase 4-an orchestrator of the integrated stress response-that correlated with and predicted YF-17D CD8(+) T cell responses with up to 90% accuracy in an independent, blinded trial. A distinct signature, including B cell growth factor TNFRS17, predicted the neutralizing antibody response with up to 100% accuracy. These data highlight the utility of systems biology approaches in predicting vaccine efficacy.
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                Author and article information

                Contributors
                : Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS Pathog
                Journal ID (publisher-id): plos
                Journal ID (pmc): plospath
                Title: PLoS Pathogens
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Print): 1553-7366
                ISSN (Electronic): 1553-7374
                Publication date Collection: October 2009
                Publication date (Print): October 2009
                Publication date (Electronic): 26 October 2009
                Volume: 5
                Issue: 10
                Electronic Location Identifier: e1000600
                Affiliations
                [1]Division of Mycobacterial Research, MRC National Institute for Medical Research, London, United Kingdom
                The Scripps Research Institute, United States of America
                Author notes
                Article
                Publisher ID: 09-PLPA-RV-1112R2
                DOI: 10.1371/journal.ppat.1000600
                PMC ID: 2745564
                PubMed ID: 19855821
                SO-VID: a394f713-2298-4da6-af2e-cd9b0c72e65b
                Copyright © Comas, Gagneux. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                Page count
                Pages: 7
                Categories
                Subject: Review
                Subject: Evolutionary Biology
                Subject: Evolutionary Biology/Genomics
                Subject: Evolutionary Biology/Microbial Evolution and Genomics
                Subject: Immunology/Immunity to Infections
                Subject: Infectious Diseases
                Subject: Infectious Diseases/Antimicrobials and Drug Resistance
                Subject: Infectious Diseases/Bacterial Infections
                Subject: Infectious Diseases/Epidemiology and Control of Infectious Diseases
                Subject: Infectious Diseases/HIV Infection and AIDS
                Subject: Microbiology
                Subject: Microbiology/Immunity to Infections
                Subject: Microbiology/Innate Immunity
                Subject: Microbiology/Medical Microbiology
                Subject: Public Health and Epidemiology
                Subject: Public Health and Epidemiology/Global Health

                ScienceOpen disciplines: Infectious disease & Microbiology
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology

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