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Mycobacterial Pathogenomics and Evolution

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  • Authors: Daria Bottai1, Timothy P. Stinear2, Philip Supply3, Roland Brosch4
  • Editors: Graham F. Hatfull5, William R. Jacobs Jr.6
    Affiliations: 1: Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Università di Pisa, Pisa, Italy; 2: Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia; 3: CNRS UMR 8204; INSERM, U1019; Center for Infection and Immunity of Lille, Institut Pasteur de Lille; and Université Lille Nord de France, Lille, France; 4: Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, Paris, France; 5: University of Pittsburgh, Pittsburgh, PA 15260; 6: Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461
  • Source: microbiolspec January 2014 vol. 2 no. 1 doi:10.1128/microbiolspec.MGM2-0025-2013
  • Received 03 September 2013 Accepted 12 September 2013 Published 31 January 2014
  • Roland Brosch, [email protected]
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  • Abstract:

    Most mycobacterial species are harmless saprophytes, often found in aquatic environments. A few species seem to have evolved from this pool of environmental mycobacteria into major human pathogens, such as , the agent of tuberculosis, , the leprosy bacillus, and , the agent of Buruli ulcer. While the pathogenicity of relates to the acquisition of a large plasmid encoding a polyketide-derived toxin, the molecular mechanisms by which or have evolved to cause disease are complex and involve the interaction between the pathogen and the host.

    Here we focus on and closely related mycobacteria and discuss insights gained from recent genomic and functional studies. Comparison of genome data with sequences from nontuberculous mycobacteria, such as or , provides a perception of the more distant evolution of , while the recently accomplished genome sequences of multiple tubercle bacilli with smooth colony morphology, named , have allowed the ancestral gene pool of tubercle bacilli to be estimated. The resulting findings are instrumental for our understanding of the pathogenomic evolution of tuberculosis-causing mycobacteria. Comparison of virulent and attenuated members of the complex has further contributed to identification of a specific secretion pathway, named ESX or Type VII secretion. The molecular machines involved are key elements for mycobacterial pathogenicity, strongly influencing the ability of to cope with the immune defense mounted by the host.

  • Citation: Bottai D, Stinear T, Supply P, Brosch R. 2014. Mycobacterial Pathogenomics and Evolution. Microbiol Spectrum 2(1):MGM2-0025-2013. doi:10.1128/microbiolspec.MGM2-0025-2013.


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Most mycobacterial species are harmless saprophytes, often found in aquatic environments. A few species seem to have evolved from this pool of environmental mycobacteria into major human pathogens, such as , the agent of tuberculosis, , the leprosy bacillus, and , the agent of Buruli ulcer. While the pathogenicity of relates to the acquisition of a large plasmid encoding a polyketide-derived toxin, the molecular mechanisms by which or have evolved to cause disease are complex and involve the interaction between the pathogen and the host.

Here we focus on and closely related mycobacteria and discuss insights gained from recent genomic and functional studies. Comparison of genome data with sequences from nontuberculous mycobacteria, such as or , provides a perception of the more distant evolution of , while the recently accomplished genome sequences of multiple tubercle bacilli with smooth colony morphology, named , have allowed the ancestral gene pool of tubercle bacilli to be estimated. The resulting findings are instrumental for our understanding of the pathogenomic evolution of tuberculosis-causing mycobacteria. Comparison of virulent and attenuated members of the complex has further contributed to identification of a specific secretion pathway, named ESX or Type VII secretion. The molecular machines involved are key elements for mycobacterial pathogenicity, strongly influencing the ability of to cope with the immune defense mounted by the host.

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Proposed scenario of pathoadaptation of tubercle bacilli from a hypothetical mycobacterial common ancestor (most recent common ancestor, MRCA), adapted from reference 49 . In the proposed evolutionary pathway strains gain specific functions (via horizontal gene transfer, recombination, mutation and/or gene loss, etc.), which allow them to better replicate and persist under the environment and temperature conditions of a niche such as human macrophages. It is plausible that the pathogenomic adaptation at some stage involved smooth tubercle bacilli/, which show a broader environmental adaptability and a genetically much larger diversity than the strains ( 35 ).

Source: microbiolspec January 2014 vol. 2 no. 1 doi:10.1128/microbiolspec.MGM2-0025-2013
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Network phylogeny inferred among the five strains subjected to complete genome sequence analysis and 39 selected genome sequences from members of the classical complex by NeighborNet analysis, based on pairwise alignments of whole-genome SNP data, which in part are also listed in the lower right portion of the figure. The color code and the naming of different phylogenetic lineages within the complex refer to the nomenclature used in reference 59 .

Source: microbiolspec January 2014 vol. 2 no. 1 doi:10.1128/microbiolspec.MGM2-0025-2013
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Working model of the type VII secretion apparatus adapted from reference 121 . Schematic representation of the core components and their interactions. Various ESX components belonging to different protein families are represented by different colors: orange, amino-terminal transmembrane protein; violet, amino-terminal transmembrane ATPase; green, integral membrane protein; red, mycosin (subtilisin-like serine protease); pink, AAA+ ATPase. Esx secreted substrates, PE and PPE proteins, as well as ESX-1-associated Esp proteins are also represented. Note that the channel drawn in the mycomembrane refers to a hypothetical protein, whose existence has not been experimentally demonstrated, and that the drawing of the mycomembrane follows a schematic representation of reference 17 .

Source: microbiolspec January 2014 vol. 2 no. 1 doi:10.1128/microbiolspec.MGM2-0025-2013
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Ratios of nonsynonymous versus synonymous SNPs in gene categories

Source: microbiolspec January 2014 vol. 2 no. 1 doi:10.1128/microbiolspec.MGM2-0025-2013

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