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      Deciphering the unexplored Leptospira diversity from soils uncovers genomic evolution to virulence

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          Abstract

          Despite recent advances in our understanding of the genomics of members of the genus Leptospira, little is known on how virulence has emerged in this heterogeneous bacterial genus as well as on the lifestyle of pathogenic members of the genus Leptospira outside animal hosts. Here, we isolated 12 novel species of the genus Leptospira from tropical soils, significantly increasing the number of known species to 35 and finding evidence of highly unexplored biodiversity in the genus. Extended comparative phylogenomics and pan-genome analyses at the genus level by incorporating 26 novel genomes, revealed that, the traditional leptospiral ‘pathogens’ cluster, as defined by their phylogenetic position, can be split in two groups with distinct virulence potential and accessory gene patterns. These genomic distinctions are strongly linked to the ability to cause or not severe infections in animal models and humans. Our results not only provide new insights into virulence evolution in the members of the genus Leptospira, but also lay the foundations for refining the classification of the pathogenic species.

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          Most cited references30

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          The Pfam protein families database.

          Pfam is a large collection of protein families and domains. Over the past 2 years the number of families in Pfam has doubled and now stands at 6190 (version 10.0). Methodology improvements for searching the Pfam collection locally as well as via the web are described. Other recent innovations include modelling of discontinuous domains allowing Pfam domain definitions to be closer to those found in structure databases. Pfam is available on the web in the UK (http://www.sanger.ac.uk/Software/Pfam/), the USA (http://pfam.wustl.edu/), France (http://pfam.jouy.inra.fr/) and Sweden (http://Pfam.cgb.ki.se/).
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            eggNOG v3.0: orthologous groups covering 1133 organisms at 41 different taxonomic ranges

            Orthologous relationships form the basis of most comparative genomic and metagenomic studies and are essential for proper phylogenetic and functional analyses. The third version of the eggNOG database (http://eggnog.embl.de) contains non-supervised orthologous groups constructed from 1133 organisms, doubling the number of genes with orthology assignment compared to eggNOG v2. The new release is the result of a number of improvements and expansions: (i) the underlying homology searches are now based on the SIMAP database; (ii) the orthologous groups have been extended to 41 levels of selected taxonomic ranges enabling much more fine-grained orthology assignments; and (iii) the newly designed web page is considerably faster with more functionality. In total, eggNOG v3 contains 721 801 orthologous groups, encompassing a total of 4 396 591 genes. Additionally, we updated 4873 and 4850 original COGs and KOGs, respectively, to include all 1133 organisms. At the universal level, covering all three domains of life, 101 208 orthologous groups are available, while the others are applicable at 40 more limited taxonomic ranges. Each group is amended by multiple sequence alignments and maximum-likelihood trees and broad functional descriptions are provided for 450 904 orthologous groups (62.5%).
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              Global Burden of Leptospirosis: Estimated in Terms of Disability Adjusted Life Years

              Background Leptospirosis, a spirochaetal zoonosis, occurs in diverse epidemiological settings and affects vulnerable populations, such as rural subsistence farmers and urban slum dwellers. Although leptospirosis can cause life-threatening disease, there is no global burden of disease estimate in terms of Disability Adjusted Life Years (DALYs) available. Methodology/Principal Findings We utilised the results of a parallel publication that reported global estimates of morbidity and mortality due to leptospirosis. We estimated Years of Life Lost (YLLs) from age and gender stratified mortality rates. Years of Life with Disability (YLDs) were developed from a simple disease model indicating likely sequelae. DALYs were estimated from the sum of YLLs and YLDs. The study suggested that globally approximately 2·90 million DALYs are lost per annum (UIs 1·25–4·54 million) from the approximately annual 1·03 million cases reported previously. Males are predominantly affected with an estimated 2·33 million DALYs (UIs 0·98–3·69) or approximately 80% of the total burden. For comparison, this is over 70% of the global burden of cholera estimated by GBD 2010. Tropical regions of South and South-east Asia, Western Pacific, Central and South America, and Africa had the highest estimated leptospirosis disease burden. Conclusions/Significance Leptospirosis imparts a significant health burden worldwide, which approach or exceed those encountered for a number of other zoonotic and neglected tropical diseases. The study findings indicate that highest burden estimates occur in resource-poor tropical countries, which include regions of Africa where the burden of leptospirosis has been under-appreciated and possibly misallocated to other febrile illnesses such as malaria.
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                Author and article information

                Journal
                Microb Genom
                Microb Genom
                MGen
                Microbial Genomics
                Microbiology Society
                2057-5858
                January 2018
                3 January 2018
                3 January 2018
                : 4
                : 1
                : e000144
                Affiliations
                [ 1]Institut Pasteur in New Caledonia, Institut Pasteur International Network, Leptospirosis Research and Expertise Unit , Noumea, New Caledonia
                [ 2]Institut Pasteur Montevideo, Bioinformatics Unit , Uruguay
                [ 3]Institut Pasteur, Unité de Biologie des Spirochètes , 28 rue du docteur Roux, 75724 Paris Cedex 15, France
                Author notes
                *Correspondence: Mathieu Picardeau, mathieu.picardeau@ 123456pasteur.fr
                [†]

                These authors contributed equally to this work

                Article
                mgen000144
                10.1099/mgen.0.000144
                5857368
                29310748
                96922782-4288-46b3-b1f6-a7f18b62a1a2
                © 2018 The Authors

                This is an open access article under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.

                History
                : 18 September 2017
                : 27 November 2017
                Funding
                Funded by: AXA Research Fund
                Award ID: 15-AXA-PDOC-037
                Funded by: Agencia Nacional de Investigación e Innovación
                Award ID: POS_NAC_2016_1_131079
                Funded by: Fondo de Convergencia Estructural del Mercosur (FOCEM)
                Award ID: grant COF 04/11
                Funded by: Institut Pasteur International Network
                Award ID: Calmette & Yersin 2017-2019
                Categories
                Research Article
                Microbial Evolution and Epidemiology: Zoonosis/Anthroponosis
                Custom metadata
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                leptospira,genomics,evolution,virulence,ecology
                leptospira, genomics, evolution, virulence, ecology

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