The rise and fall of theMycobacterium tuberculosis genome
ABSTRACT When studied from the perspective of non-tuberculous mycobacteria (NTM) it is apparent that Mycobacterium tuberculosis has undergone a biphasic evolutionary process involving genome expansion (gene acquisition and duplication) and reductive evolution (deletions). This scheme can instruct descriptive and experimental studies that determine the importance of ancestral events (including horizontal gene transfer) in shaping the present-day pathogen. For example, heterologous complementation in an NTM can test the functional importance of M. tuberculosis-specific genetic insertions. An appreciation of both phases of M. tuberculosis evolution is expected to improve our fundamental understanding of its pathogenicity and facilitate the evaluation of novel diagnostics and vaccines.
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- "Key genes acquired by HGT include those coding for mycobacterial lipids, transferases and proteins related to adaptation to anaerobic conditions  . M. kansasii still causes pulmonary disease in Silesian and South African miners, the bacterium being contracted from water in showers . In developing a coherent evolutionary route, the pathway from M. kansasii, through " M. canettii " , to M. tuberculosis is a good working hypothesis. "
ABSTRACT: Mycobacterium tuberculosis has a cell envelope incorporating a peptidoglycan-linked arabinogalactan esterified by long-chain mycolic acids. A range of "free" lipids are associated with the "bound" mycolic acids, producing an effective envelope outer membrane. The distribution of these lipids is discontinuous among mycobacteria and such lipids have proven potential for biomarker use in tracing the evolution of tuberculosis. A plausible evolutionary scenario involves progression from an environmental organism, such as Mycobacterium kansasii, through intermediate "smooth" tubercle bacilli, labelled "Mycobacterium canettii"; cell envelope lipid composition possibly correlates with such a progression. M. kansasii and "M. canettii" have characteristic lipooligosaccharides, associated with motility and biofilms, and glycosyl phenolphthiocerol dimycocerosates ("phenolic glycolipids"). Both these lipid classes are absent in modern M. tuberculosis sensu stricto, though simplified phenolic glycolipids remain in certain current biotypes. Dimycocerosates of the phthiocerol family are restricted to smaller phthiodiolone diesters in M. kansasii. Diacyl and pentaacyl trehaloses are present in "M. canettii" and M. tuberculosis, accompanied in the latter by related sulfated acyl trehaloses. In comparison with environmental mycobacteria, subtle modifications in mycolic acid structures in "M. canettii" and M. tuberculosis are notable. The probability of essential tuberculosis evolution taking place in Pleistocene megafauna, rather than Homo sapiens, is reemphasised. Copyright © 2015 Elsevier Ltd. All rights reserved.Tuberculosis (Edinburgh, Scotland) 02/2015; 95(Suppl.):S133-S139. DOI:10.1016/j.tube.2015.02.009 · 3.50 Impact Factor
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- "Finally, some host-adapted pathogenic bacteria, such as My. tuberculosis and the asymptomatic bacteriuria (ABU) strains of Escherichia coli, display moderate genome downsizing without massive IS expansion (Zdziarski et al. 2008; Veyrier et al. 2011). In such cases, the decrease in genome size probably results from the excision of mobile genetic elements. "
ABSTRACT: Bacteria of the genus Xenorhabdus are symbionts of soil entomopathogenic nematodes of the genus Steinernema. This symbiotic association constitutes an insecticidal complex active against a wide range of insect pests. Unlike other Xenorhabdus species, Xenorhabdus poinarii is avirulent when injected into insects in the absence of its nematode host. We sequenced the genome of the X. poinarii strain G6 and the closely related but virulent Xenorhabdus doucetiae strain FRM16. G6 had a smaller genome (500-700 kb smaller) than virulent Xenorhabdus strains and lacked genes encoding potential virulence factors (haemolysins, type 5 secretion systems, enzymes involved in the synthesis of secondary metabolites, toxin-antitoxin systems). The genomes of all the X. poinarii strains analysed here had a similar small size. We did not observe the accumulation of pseudogenes, insertion sequences or decrease in coding density usually seen as a sign of genomic erosion driven by genetic drift in host-adapted bacteria. Instead, genome reduction of X. poinarii seems to have been mediated by the excision of genomic blocks from the flexible genome, as reported for the genomes of attenuated free pathogenic bacteria and some facultative mutualistic bacteria growing exclusively within hosts. This evolutionary pathway probably reflects the adaptation of X. poinarii to specific host.Genome Biology and Evolution 06/2014; 6(6). DOI:10.1093/gbe/evu119 · 4.53 Impact Factor
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- "As the enzymes encoded within this island have been observed to catalyze the transfer of functional groups from one molecule to another, they may play an important role at “decorating” existing mycobacterial products and fine-tuning host responses toward the organism to optimize its intracellular survival (Veyrier et al., 2011). "
ABSTRACT: The genus Mycobacterium is comprised of more than 150 species that reside in a wide variety of habitats. Most mycobacteria are environmental organisms that are either not associated with disease or are opportunistic pathogens that cause non-transmissible disease in immunocompromised individuals. In contrast, a small number of species, such as the tubercle bacillus, Mycobacterium tuberculosis, are host-adapted pathogens for which there is no known environmental reservoir. In recent years, gene disruption studies using the host-adapted pathogen have uncovered a number of "virulence factors," yet genomic data indicate that many of these elements are present in non-pathogenic mycobacteria. This suggests that much of the genetic make-up that enables virulence in the host-adapted pathogen is already present in environmental members of the genus. In addition to these generic factors, we hypothesize that molecules elaborated exclusively by professional pathogens may be particularly implicated in the ability of M. tuberculosis to infect, persist, and cause transmissible pathology in its host species, Homo sapiens. One approach to identify these molecules is to employ comparative analysis of mycobacterial genomes, to define evolutionary events such as horizontal gene transfer (HGT) that contributed M. tuberculosis-specific genetic elements. Independent studies have now revealed the presence of HGT genes in the M. tuberculosis genome and their role in the pathogenesis of disease is the subject of ongoing investigations. Here we review these studies, focusing on the hypothesized role played by HGT loci in the emergence of M. tuberculosis from a related environmental species into a highly specialized human-adapted pathogen.Frontiers in Microbiology 04/2014; 5:139. DOI:10.3389/fmicb.2014.00139 · 3.94 Impact Factor