IS<i>6110</i> functions as a mobile, monocyte‐activated promoter in <i>Mycobacterium tuberculosis</i>

Safi, Hassan; Barnes, Peter F.; Lakey, David; Shams, Homayoun; Samten, Buka; Vankayalapati, Ramakrishna; Howard, Susan T.

doi:10.1111/j.1365-2958.2004.04037.x

Cited by 71 publications

(68 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IS6110 can upregulate downstream genes through an outward-directed promoter in its 3Ј end (27). Sequence analysis of the mutant isolates showed that all the IS6110 insertions, either within the coding sequence of the plcD gene, or in the flanking region of plcD, resulted in a partial deletion of the coding sequence of the plcD gene.…”

Section: Table 3 Multivariate Logistic Regression Analysis Showing Tmentioning

confidence: 99%

Clinical Relevance of Mycobacterium tuberculosis plcD Gene Mutations

Yang

Kong

et al. 2005

Am J Respir Crit Care Med

View full text Add to dashboard Cite

To identify Mycobacterium tuberculosis virulence factors, we integrated comparative genomics and epidemiologic data analysis to investigate the relationship between certain genomic insertions and deletions in the phospholipase-C gene D (plcD) with the clinical presentation of tuberculosis (TB). Four hundred ninety-six wellcharacterized M. tuberculosis clinical isolates were studied. Approximately 30% (147) of the isolates had an interruption of the plcD gene. Patients infected with the plcD mutant were twice as likely to have extrathoracic disease as those infected by a strain without an interruption (adjusted odds ratio, 2.19; 95% confidence interval, 1.27, 3.76). When we limited the analysis to the 275 isolates with distinct DNA fingerprint patterns, we observed the same association (adjusted odds ratio, 2.74; 95% confidence interval, 1.35, 5.56). Furthermore, the magnitude of the association appeared to differ with the type of extrathoracic TB. Our findings suggest that the plcD gene of M. tuberculosis is potentially involved in the pathogenesis of TB, and the clinical presentation of the disease may be influenced by the genetic variability of the plcD region. Keywords: extrathoracic tuberculosis; pathogenesis; virulence factorsTuberculosis (TB) is a major cause of morbidity and mortality worldwide (1). The lack of an effective vaccine to prevent those who are latently infected with Mycobacterium tuberculosis from developing active disease, the variable results obtained in bacillus Calmette-Gué rin vaccine efficacy trials, the emergence of multidrug-resistant TB worldwide, and the increasing coinfection of HIV with M. tuberculosis in many regions of the world (2-4) highlight the need for a highly effective vaccine and new antimicrobial agents. Identification of the M. tuberculosis factors that contribute to the pathogenesis of TB is necessary if the goal to develop a more effective vaccine is to be reached.To date, identification of M. tuberculosis virulence factors has been based primarily on in vitro and animal studies (5). Although these studies have increased our understanding of the function of a number of M. tuberculosis genes and the impact of gene products on the organisms' behavior in various in vitro and in vivo models, correlation of in vitro findings and animal studies with the pathogenesis of human disease remains challenging (5). An alternative strategy to identify M. tuberculosis virulence factors (6-11) combines comparative genomics to identify genome alteration with epidemiologic methods, to assess associations between genetic polymorphisms and clinical characteristics of the disease. Previous comparative genomic studies have identified large sequence deletions in multiple regions of the M. tuberculosis genome (6,11,12). However, the epidemiologic and clinical phenotypes of these genomic alterations remain largely unknown. Of the previously reported genomic deletions, the region containing the phospholipase-C gene D (plcD) (6) is of particular interest because of the role of plc in the pathog...

show abstract

Section: Table 3 Multivariate Logistic Regression Analysis Showing Tmentioning

confidence: 99%

Clinical Relevance of Mycobacterium tuberculosis plcD Gene Mutations

Yang

Kong

et al. 2005

Am J Respir Crit Care Med

View full text Add to dashboard Cite

show abstract

“…Transposable elements can also act by modifying the expression of neighbouring genes at the integration site, or by promoting huge genomic rearrangements when they are substrates for homologous recombination (Casacuberta & González, 2013;Mahillon & Chandler, 1998;Maruyama et al, 2009). Some well-described bacterial examples are the activation of the cryptic bgl and cel operons required for utilization of b-glucoside sugars in Escherichia coli by disruption of silencer elements around the promoter region by IS1, IS2 or IS5 transposition; IS1 insertion into the mgl locus improving the glucose transport and fitness of E. coli; ISS12 integration into the srpS gene increasing the resistance of Pseudomonas putida to toluene by derepressing the genes encoding an inducible solvent resistance pump; or IS6110 controlling transcription of Mycobacterium tuberculosis genes (including the phoP virulence gene) downstream of its integration site through an outward-directed promoter located at its 39 end (Hall, 1998;Notley-McRobb & Ferenci, 1999;Parker & Hall, 1990;Safi et al, 2004;Soto et al, 2004;Wery et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Physiological impact of transposable elements encoding DDE transposases in the environmental adaptation of Streptococcus agalactiae

Fléchard

Gilot

2014

Microbiology

View full text Add to dashboard Cite

We have referenced and described Streptococcus agalactiae transposable elements encoding DDE transposases. These elements belonged to nine families of insertion sequences (ISs) and to a family of conjugative transposons (TnGBSs). An overview of the physiological impact of the insertion of all these elements is provided. DDE-transposable elements affect S. agalactiae in a number of aspects of its capability to adapt to various environments and modulate the expression of several virulence genes, the scpB-lmB genomic region and the genes involved in capsule expression and haemolysin transport being the targets of several different mobile elements. The referenced mobile elements modify S. agalactiae behaviour by transferring new gene(s) to its genome, by modifying the expression of neighbouring genes at the integration site or by promoting genomic rearrangements. Transposition of some of these elements occurs in vivo, suggesting that by dynamically regulating some adaptation and/or virulence genes, they improve the ability of S. agalactiae to reach different niches within its host and ensure the 'success' of the infectious process.

show abstract

“…The promoter carried by IS6110 has the relevance of being activated inside monocytes (Safi et al, 2004) and its activity was demonstrated in several genes not only in the strain H37Rv but also in other clinical strains including Beijing strains (Safi et al, 2004). Remarkably that promoter activity has been demonstrated by the upregulation of the main two-component system of this bacterium, namely phoP/phoR (Soto et al, 2004).…”

Section: Switching On and Off Genesmentioning

confidence: 92%

“…This could be due to a polar effect of the IS and also due to the presence of an outward promoter that was identified close to the 3'-end of IS6110 (Safi et al, 2004;Soto et al, 2004).…”

Section: Switching On and Off Genesmentioning

confidence: 99%

“…Many functions have been shown by the IS6110: (i) activation of genes during infection (Safi et al, 2004) (ii) participation in the evolution as an epidemiological marker (van Embden et al, 1993) (iii) activation of downstream genes with an activity promoter orientationdependent (Soto et al, 2004). Finally, it has been suggested that the presence of IS6110 in M. bovis could participate in the adaptation of this bacteria to a particular host, animal or human (Otal et al, 2008).…”

Section: Fig 1 Structural Organization Of Is6110mentioning

confidence: 99%

See 1 more Smart Citation