Characterization of an IS-like element from Mycobacterium tuberculosis

Mariani, Francesca; Piccolella, Enza; Colizzi, Vittorio; Rappuoli, Rino; Gross, Roy

doi:10.1099/00221287-139-8-1767

Cited by 37 publications

(31 citation statements)

References 27 publications

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“…The loss of a family of IS elements from a taxonomic group may be countered by the gain of other IS elements from distantly related taxa. Evidence has been uncovered for the occasional movement of transposable elements across taxonomic boundaries in the M. tuberculosis complex (28). Horizontal transfer of transposons also has been well studied in Drosophila species (29) and across a wider range of arthropods (30).…”

Section: Discussionmentioning

confidence: 99%

The dynamics of repeated elements: Applications to the epidemiology of tuberculosis

Tanaka¹

2000

Proceedings of the National Academy of Sciences

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We propose a stepwise mutation model to describe the dynamics of DNA fingerprint variation in Mycobacterium tuberculosis. The genome of M. tuberculosis carries insertion sequences (IS6110) that are relatively stable over time periods of months but have an observable transposition rate over longer time scales. Variability in copy number and genomic location of (IS6110) can be harnessed to generate a DNA fingerprint for each strain, by digesting the genome with a restriction enzyme and using a portion of the element as a probe for Southern blots. The number of bands found for a given genome approximates the number of copies of IS6110 it carries. A large data set of such fingerprints from tuberculosis (TB) cases in San Francisco provides an observed distribution of IS6110 copy number. Implementation of the model through deterministic and stochastic simulation indicates some general features of IS͞TB dynamics. By comparing observations with outcomes of the model, we conclude that the IS͞TB system is very heterogeneous and far from equilibrium. We find that the transposition parameters have a much stronger effect than the epidemic parameters on copy number distribution. E fficient molecular methods have allowed the recent genetic characterization of parasitic agents. Such empirical work greatly enhances our understanding of the epidemiology of human diseases (1-4). These new data are the stimulus for the development of theoretical and quantitative understanding of how genetic variability among strains interacts with epidemic processes. The molecular epidemiology of tuberculosis (TB) has been well developed. The insertion sequence (IS) 6110 in the genome of Mycobacterium tuberculosis is stable on the short time scale of months, while transposing at an observable rate over longer time periods. By digesting the genome with the restriction enzyme PvuII and using a portion of the element as a probe for Southern blotting, strains can be distinguished by the resulting DNA fingerprints (2). The number of bands in each blot indicates the number of copies of IS in the isolated genome.The essential features of TB dynamics recently have been explored (5-7). Those studies take into account the various important aspects of the disease; for instance, a fraction of newly acquired infections progress to the disease immediately while the remainder enter a potentially long period of latent infection. Using estimates of epidemiological parameters from the empirical literature, those authors quantitatively characterize the length of epidemics and assess the efficacy of control strategies.Several theoretical studies have investigated transposon dynamics. Many of these are constructed for diploid genomes, particularly Drosophila (8-10). Sawyer and Hartl (11) and Moody (12) treat stochastic models of transposable elements in prokaryotes (IS elements), though without consideration of epidemic circumstances. Both studies allow a degree of horizontal transmission. The latter includes replicative transposition (increase by one copy) and deletio...

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Section: Discussionmentioning

confidence: 99%

The dynamics of repeated elements: Applications to the epidemiology of tuberculosis

Tanaka¹

2000

Proceedings of the National Academy of Sciences

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“…IS1248 from P. denitrificans closely resembles IS869, which resides on the Ti plasmid of Agrobacterium tumefaciens (18). Other members belonging to this group of IS elements include IS427, also found in A. tumefaciens (7); IS402 from Pseudomonas cepacia (10); ISmyco, found in Mycobacterium tuberculosis (16); IS1106 from Neisseria meningitidis (13); Tn4811 from Streptomyces lividans (4); ISRm4 of Rhizobium meliloti (23); another previously identified IS found in R. meliloti (19); and IS1031 of Acetobacter xylinum (6). ISmyco, the IS element from R. meliloti, and IS1031 have only single ORFs.…”

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Integration of heterologous DNA into the genome of Paracoccus denitrificans is mediated by a family of IS1248-related elements and a second type of integrative recombination event

1995

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All members of the IS1248 family residing in the genome of Paracoccus denitrificans have been isolated by using a set of insertion sequence entrapment vectors. The family consists of five closely related members that integrate the entrapment vectors at distinct sites. One of these, IS1248b, was sequenced and, except for a single base change, shown to be identical to the previously isolated IS1248a. Southern analysis of genomic DNA with labeled IS1248 revealed different hybridization patterns for different isolates of P. denitrificans and Thiosphaera pantotropha. No hybridization was observed with DNA from Thiobacillus versutus and more distantly related species. From a comparison of the fingerprints it was shown that one of the members of the IS1248 family found in P. denitrificans DSM413 is absent in strain NCIB8944, although they are catalogued in international strain catalogues as identical strains. Furthermore, strains Pd1222 and Pd1235, both derivatives of P. denitrificans DSM413, were shown to have different patterns of IS1248 hybridizing restriction fragments. In 14 of 18 strains, the entrapment vectors used in this study were incorporated into the genome via IS1248-mediated cointegrate formation. In the other four strains, the entrapment vectors were shown to be integrated through a different mechanism not involving IS1248.

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“…This region contains a small ORF, ORF1, with a probable start codon (ATG) at nt 3404 and a TGA stop codon at nt 3129 that would encode a polypeptide having 92 amino acid residues. A database search using the TFASTA program (7) indicated that the deduced product of ORF1 is similar to the putative transposases from the insertion sequences IS6501 (32), IS711 (15), and IS427 (5) and the insertion sequence-like element from M. tuberculosis (28). The observed similarities to insertion sequences do not establish that the 866-nt region contains an insertion element, since this region could be merely the remnant of a past insertional event.…”

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Cloning and characterization of the Streptomyces peucetius dnrQS genes encoding a daunosamine biosynthesis enzyme and a glycosyl transferase involved in daunorubicin biosynthesis

et al. 1995

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The dnrQS genes from the daunorubicin producer Streptomyces peucetius were characterized by DNA sequencing, complementation analysis, and gene disruption. The dnrQ gene is required for daunosamine biosynthesis, and dnrS appears to encode a glycosyltransferase for the addition of the 2,3,6-trideoxy-3-aminohexose, daunosamine, to -rhodomycinone.Dideoxy-and trideoxyaminohexoses are essential components of many biologically active natural products (23,43), including the antitumor antibiotics daunorubicin (DNR) and doxorubicin (10). Although the important biological roles played by deoxyhexoses have been well recognized, little is known about their biosynthesis (13,23,36), with the exception of the 3,6-dideoxyhexose ascarylose, which has been well characterized at both the genetic and biochemical levels (24,38). An understanding of the biosynthesis of the 2,6-dideoxy-, 4,6-dideoxy-, and trideoxyaminohexoses that are commonly found in natural products is beginning to emerge, based in part on extension from knowledge of the 3,6-dideoxyhexoses (23,39). It has been demonstrated in a number of instances that these sugars are derived from the corresponding hexose nucleosides (33,35,40) by the action of 4,6-dehydratases (22,37,40,42) to form 4-keto-6-deoxyhexose nucleotides. DNR and doxorubicin contain the 2,3,6-trideoxy-3-aminohexose daunosamine ( Fig. 1), which is required for their antitumor activity (10). A putative TDP-glucose synthetase gene, dnrL (11), has been identified in the DNR gene cluster (12,25,31) of Streptomyces peucetius ATCC 29050, and a TDP-glucose-4,6-dehydratase has been partially purified from this organism (37). Surprisingly, the dnrM gene, which is located adjacent to dnrL in the DNR gene cluster, encodes a 4,6-dehydratase homolog that appears to be nonfunctional because of a frameshift mutation which results in the synthesis of a truncated protein (11). These results led to the detection of another 4,6-dehydratase gene (11) located outside the DNR gene cluster which encodes the enzyme described by Thompson et al. (37). Analysis of the dnrJ gene (25) has led to the hypothesis that the DnrJ protein is likely to function as a coenzyme B 6 -dependent transaminase which catalyzes the addition of an amino group to the C-3 position of daunosamine (25, 39).Here we report the characterization of the S. peucetius dnrQ and dnrS genes on the basis of DNA sequencing, gene inactivation, and complementation experiments. We conclude that dnrS is likely to encode a glycosyltransferase that catalyzes the addition of daunosamine to the aglycone portion of DNR and that dnrQ encodes a product that is required for daunosamine biosynthesis.Cloning and expression of the dnrS gene. The dnrS gene was subcloned from the DNR gene cluster (25, 31) by complementation of the S. peucetius mutant strain H6125 (18,19,31). This strain accumulates ε-rhodomycinone, the aglycone portion of DNR (Fig. 1). In order to ascertain the nature of the mutation(s) in the H6125 strain, bioconversion experiments were conducted as previously descr...

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Characterization of an IS-like element from Mycobacterium tuberculosis

Cited by 37 publications

References 27 publications

The dynamics of repeated elements: Applications to the epidemiology of tuberculosis

The dynamics of repeated elements: Applications to the epidemiology of tuberculosis

Integration of heterologous DNA into the genome of Paracoccus denitrificans is mediated by a family of IS1248-related elements and a second type of integrative recombination event

Cloning and characterization of the Streptomyces peucetius dnrQS genes encoding a daunosamine biosynthesis enzyme and a glycosyl transferase involved in daunorubicin biosynthesis

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