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Plasmids – potential tool for the investigation of gene transfer in Mycobacterium tuberculosis

T. Dam, Paramita Das

  • 1Room no. 204, Mudd Hall, Department of Biology, Johns Hopkins University, 3400 (N) Charles Street, Baltimore, MD 21218, USA
  • 2Department of Zoology, Visva Bharati University, Santiniketan, Birbhum, West Bengal 731235, India
  • Correspondence
    T. Dam
    (tdam1{at}jhmi.edu)

    • Journal of Medical Microbiology 2006; 55(4):479–480 · https://doi.org/10.1099/jmm.0.46258-0

    View at publisher PubMed

    Abstract

    Changes in the genetic repertoire by the acquisition of new genetic material through horizontal gene transfer is an important phenomenon in the evolution of many bacteria (Ochman & Moran, 2001). Transferred genes may either provide small but evolutionary important contributions to fitness or confer condition-specific advantages, facilitating adaptation to a new environment (Pal et al., 2005). Many bacterial pathogens have evolved the capacity to produce virulence factors that are directly involved in infection and disease. Acquiring virulence through horizontal gene transfer is the most common mechanism of gaining new genetic information (Ochman et al., 2000; Morschhauser et al., 2000; Hacker & Kaper, 2000; Ziebuhr et al., 1999). The need for information regarding gene transfer has prompted further investigation of different pathogenic organisms. Understanding gene transfer will explain the pathogenicity of the organism in the host.

    Mycobacterium tuberculosis is a globally successful pathogen causing tuberculosis (TB), a leading cause of death worldwide (Drobniewski et al., 2003). It was estimated that there were 8·8 million new TB cases in the world in 2003, with a prevalence of 15·4 million and 2 million deaths from TB (World Health Organization, 2005). In spite of significant research into the understanding of the pathogenicity of the organism, important gaps in our knowledge remain. M. tuberculosis harbours 19 genes of eukaryotic origin and has the highest number of eukaryotic–prokaryotic inter-kingdom gene fusions of all sequenced bacterial genomes (Wolf et al., 2000; Gamieldien et al., 2002). It would be reasonable to speculate that this organism may have obtained virulence gene(s) from other organisms, so the investigation of gene transfer may lead to a significant improvement in the understanding of the pathogenicity of this organism. Identifying a suitable tool that will allow gene transfer investigations among mycobacteria will be extremely useful.

    Screening of plasmids from mycobacteria has been performed in various studies in order to demonstrate an epidemiological marker in mycobacteria (Gangadharam et al., 1988; Dam et al., 2000). Sequence analysis of the plasmid pCLP from Mycobacterium celatum revealed the presence of a similar sequence in M. tuberculosis that includes the putative resolvase and transposase of IS1535 (Dantec et al., 2001). As genes harboured in plasmids are more prone to transfer than chromosomally located genes, a plasmid can serve as a vehicle for transferring genes among mycobacteria. This is further evidenced in another report that showed the presence of an 18 kb plasmid in the M. tuberculosis H37Rv strain (Katti, 2001). This finding provides direct evidence of gene transfer in M. tuberculosis although an earlier study reported the absence of plasmids in M. tuberculosis (Zainuddin & Dale, 1990). The presence of the same plasmid (18 kb) in several other mycobacterial species further supports the gene transfer phenomenon among mycobacteria.

    Post-genomic tools are continuously generating information on mycobacteria. The fatty acid biosynthetic pathway, especially mycolic acid (targeted by many drugs), has been extensively modified in M. tuberculosis by horizontal gene transfer as shown by phylogenetic analysis of the M. tuberculosis genome with 58 complete bacterial genomes (Kinsella et al., 2003). However, in the absence of more direct evidence, the plasmid is clearly a promising tool for the investigation of gene transfer among mycobacteria, and the 18 kb plasmid of M. tuberculosis has potential as such a tool.

    Changes in the genetic repertoire by the acquisition of new genetic material through horizontal gene transfer is an important phenomenon in the evolution of many bacteria (Ochman & Moran, 2001). Transferred genes may either provide small but evolutionary important contributions to fitness or confer condition-specific advantages, facilitating adaptation to a new environment (Pal et al., 2005). Many bacterial pathogens have evolved the capacity to produce virulence factors that are directly involved in infection and disease. Acquiring virulence through horizontal gene transfer is the most common mechanism of gaining new genetic information (Ochman et al., 2000; Morschhauser et al., 2000; Hacker & Kaper, 2000; Ziebuhr et al., 1999). The need for information regarding gene transfer has prompted further investigation of different pathogenic organisms. Understanding gene transfer will explain the pathogenicity of the organism in the host.

    Mycobacterium tuberculosis is a globally successful pathogen causing tuberculosis (TB), a leading cause of death worldwide (Drobniewski et al., 2003). It was estimated that there were 8·8 million new TB cases in the world in 2003, with a prevalence of 15·4 million and 2 million deaths from TB (World Health Organization, 2005). In spite of significant research into the understanding of the pathogenicity of the organism, important gaps in our knowledge remain. M. tuberculosis harbours 19 genes of eukaryotic origin and has the highest number of eukaryotic–prokaryotic inter-kingdom gene fusions of all sequenced bacterial genomes (Wolf et al., 2000; Gamieldien et al., 2002). It would be reasonable to speculate that this organism may have obtained virulence gene(s) from other organisms, so the investigation of gene transfer may lead to a significant improvement in the understanding of the pathogenicity of this organism. Identifying a suitable tool that will allow gene transfer investigations among mycobacteria will be extremely useful.

    Screening of plasmids from mycobacteria has been performed in various studies in order to demonstrate an epidemiological marker in mycobacteria (Gangadharam et al., 1988; Dam et al., 2000). Sequence analysis of the plasmid pCLP from Mycobacterium celatum revealed the presence of a similar sequence in M. tuberculosis that includes the putative resolvase and transposase of IS1535 (Dantec et al., 2001). As genes harboured in plasmids are more prone to transfer than chromosomally located genes, a plasmid can serve as a vehicle for transferring genes among mycobacteria. This is further evidenced in another report that showed the presence of an 18 kb plasmid in the M. tuberculosis H37Rv strain (Katti, 2001). This finding provides direct evidence of gene transfer in M. tuberculosis although an earlier study reported the absence of plasmids in M. tuberculosis (Zainuddin & Dale, 1990). The presence of the same plasmid (18 kb) in several other mycobacterial species further supports the gene transfer phenomenon among mycobacteria.

    Post-genomic tools are continuously generating information on mycobacteria. The fatty acid biosynthetic pathway, especially mycolic acid (targeted by many drugs), has been extensively modified in M. tuberculosis by horizontal gene transfer as shown by phylogenetic analysis of the M. tuberculosis genome with 58 complete bacterial genomes (Kinsella et al., 2003). However, in the absence of more direct evidence, the plasmid is clearly a promising tool for the investigation of gene transfer among mycobacteria, and the 18 kb plasmid of M. tuberculosis has potential as such a tool.

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