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      Genomic reconnaissance of clinical isolates of emerging human pathogen Mycobacterium abscessus reveals high evolutionary potential

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          Abstract

          Mycobacterium abscessus (Ma) is an emerging human pathogen that causes both soft tissue infections and systemic disease. We present the first comparative whole-genome study of Ma strains isolated from patients of wide geographical origin. We found a high proportion of accessory strain-specific genes indicating an open, non-conservative pan-genome structure, and clear evidence of rapid phage-mediated evolution. Although we found fewer virulence factors in Ma compared to M. tuberculosis, our data indicated that Ma evolves rapidly and therefore should be monitored closely for the acquisition of more pathogenic traits. This comparative study provides a better understanding of Ma and forms the basis for future functional work on this important pathogen.

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          Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome".

          The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide screens for vaccine candidates or for antimicrobial targets. We have generated the genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans. Analysis of these genomes and those available in databases showed that the S. agalactiae species can be described by a pan-genome consisting of a core genome shared by all isolates, accounting for approximately 80% of any single genome, plus a dispensable genome consisting of partially shared and strain-specific genes. Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactiae pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes.
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            The microbial pan-genome.

            A decade after the beginning of the genomic era, the question of how genomics can describe a bacterial species has not been fully addressed. Experimental data have shown that in some species new genes are discovered even after sequencing the genomes of several strains. Mathematical modeling predicts that new genes will be discovered even after sequencing hundreds of genomes per species. Therefore, a bacterial species can be described by its pan-genome, which is composed of a "core genome" containing genes present in all strains, and a "dispensable genome" containing genes present in two or more strains and genes unique to single strains. Given that the number of unique genes is vast, the pan-genome of a bacterial species might be orders of magnitude larger than any single genome.
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              Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette-Guérin attenuation.

              The tuberculosis (TB) vaccine bacille Calmette-Guérin (BCG) is a live attenuated organism, but the mutation responsible for its attenuation has never been defined. Recent genetic studies identified a single DNA region of difference, RD1, which is absent in all BCG strains and present in all Mycobacterium tuberculosis (MTB) strains. The 9 open-reading frames predicted within this 9.5-kb region are of unknown function, although they include the TB-specific immunodominant antigens ESAT-6 and CFP-10. In this study, RD1 was deleted from MTB strain H37Rv, and virulence of H37Rv:DeltaRD1 was assessed after infections of the human macrophage-like cell line THP-1, human peripheral blood monocyte-derived macrophages, and C57BL/6 mice. In each of these systems, the H37Rv:DeltaRD1 strain was strikingly less virulent than MTB and was very similar to BCG controls. Therefore, it was concluded that genes within or controlled by RD1 are essential for MTB virulence and that loss of RD1 was important in BCG attenuation.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                11 February 2014
                2014
                : 4
                : 4061
                Affiliations
                [1 ]Genome Informatics Research Laboratory, High Impact Research (HIR) Building, University of Malaya , 50603 Kuala Lumpur, Malaysia
                [2 ]Division of Information Sciences, School of Computer Engineering, Nanyang Technological University , Singapore
                [3 ]Synthetic Biology Group , Lanzatech, Auckland, New Zealand
                [4 ]Department of Oral Biology & Biomedical Sciences, Faculty of Dentistry, University of Malaya , 50603 Kuala Lumpur, Malaysia
                [5 ]Department of Medical Microbiology, Faculty of Medicine, University of Malaya , 50603 Kuala Lumpur, Malaysia
                [6 ]CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics , Chinese Academy of Sciences, Beijing 100101, China
                [7 ]University of Chinese Academy of Sciences , Beijing 100049, China
                Author notes
                Article
                srep04061
                10.1038/srep04061
                3920477
                24515248
                c3645fef-22d9-42ab-ad57-87bef548d79b
                Copyright © 2014, Macmillan Publishers Limited. All rights reserved

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

                History
                : 26 September 2013
                : 23 January 2014
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