Identification of novel intergenic repetitive units in a mycobacterial two‐component system operon

Supply, Philip; Magdalena, Juana; Himpens, Sabine; Locht, Camille

doi:10.1046/j.1365-2958.1997.6361999.x

Cited by 199 publications

(198 citation statements)

References 44 publications

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“…While this work was under review, a report was published which describes the ETR-D locus in detail and discusses intergenic loci homologous to ETR-D, ETR-E and ETR-F (Supply et al, 1997).…”

Section: Note Added In Proofmentioning

confidence: 99%

Genetic diversity in the Mycobacterium tuberculosis complex based on variable numbers of tandem DNA repeats

1998

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Genetic loci containing variable numbers of tandem repeats (VNTR loci) form the basis for human gene mapping and identification, forensic analysis and paternity testing. The variability of bacterial tandem repeats has not been systematically studied. Eleven tandem repeat loci in the M. tuberculosis genome were analysed. Five major polymorphic tandem repeat (MPTR) loci contained 15-bp repeats with substantial sequence variation in adjacent copies. Six exact tandem repeat (ETR) loci contained large DNA repeats with identical sequences in adjacent repeats. These 11 loci were amplified in 48 strains to determine the number of tandem repeats at each locus. The strains bovis BCG substrains. Allele profiles were reproducible and stable, as demonstrated by analyses of multiple isolates of particular reference strains obtained from different laboratories. VNTR typing may be generally useful for strain differentiation and evolutionary studies in bacteria.

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“…While this work was under review, a report was published which describes the ETR-D locus in detail and discusses intergenic loci homologous to ETR-D, ETR-E and ETR-F (Supply et al, 1997).…”

Section: Note Added In Proofmentioning

confidence: 99%

Genetic diversity in the Mycobacterium tuberculosis complex based on variable numbers of tandem DNA repeats

1998

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“…Significant attention has focused on regulation of senX3-regX3 and its role in Mtb virulence (Glover et al, 2007;Himpens et al, 2000;James et al, 2012;Parish et al, 2003;Rickman et al, 2004;Rifat et al, 2009;Supply et al, 1997;Tischler et al, 2013). In Mycobacterium smegmatis, SenX3-RegX3 has been shown to control expression of IP: 54.191.190.102 On: Sat, 12 May 2018 06:44:34 phosphate-dependent genes (Glover et al, 2007), and is required for optimal growth under P i -limiting conditions (James et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Differential regulation of the two-component regulatory system senX3-regX3 in Mycobacterium tuberculosis

Rifat

Karakousis

2014

Microbiology

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The highly successful pathogen Mycobacterium tuberculosis (Mtb) has evolved strategies to adapt to various stress conditions, thus promoting survival within the infected host. The twocomponent regulatory system (2CRS) senX3-regX3, which has been implicated in the Mtb response to inorganic phosphate depletion, is believed to behave as an auto-regulatory bicistronic operon. Unlike other 2CRS, Mtb senX3-regX3 features an intergenic region (IR) containing several mycobacterium interspersed repetitive units (MIRU) of unknown function. In this study, we used a lacZ reporter system to study the promoter activity of the 59 untranslated region of senX3, and that of various numbers of MIRUs in the senX3-regX3 IR, during axenic Mtb growth in nutrient-rich broth, and upon exposure to growth-restricting conditions. Activity of the senX3 promoter was induced during phosphate depletion and nutrient starvation, and IR promoter activity under these conditions was directly proportional to the number of MIRUs present. Quantitative reverse transcriptase (qRT)-PCR analysis of exponentially growing Mtb revealed monocistronic transcription of senX3 and regX3, and, to a lesser degree, bicistronic transcription of the operon. In addition, we observed primarily monocistronic upregulation of regX3 during phosphate depletion of Mtb, which was confirmed by Northern analysis in wild-type Mtb and by RT-PCR in a senX3-disrupted mutant, while upregulation of regX3 in nutrient-starved Mtb was chiefly bicistronic. Our findings of differential regulation of senX3-regX3 highlight the potential regulatory role of MIRUs in the Mtb genome and provide insight into the regulatory mechanisms underlying Mtb adaptation to physiologically relevant conditions.

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“…Results of initial analysis performed on the patient demographic information according to the MTC strain families illustrated the potential for combining strain genotyping and demographic data. Future work will concentrate on developing methods for merging probabilistic models for spoligotyping and other MTC genotyping methods, such as mycobacterial interspersed repetitive units (Mazars et al, 2001;Supply et al, 1997;Supply et al, 2001) and IS6110-based restriction fragment length polymorphism analyses, with traditional epidemiological data.…”

Section: Discussionmentioning

confidence: 99%

Identifying Mycobacterium tuberculosis complex strain families using spoligotypes

Vitol

Driscoll

Kreiswirth³

et al. 2006

Infection, Genetics and Evolution

104

102

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We present a novel approach for analysis of Mycobacterium tuberculosis complex (MTC) strain genotyping data. Our work presents a first step in an ongoing project dedicated to the development of decision support tools for tuberculosis (TB) epidemiologists exploiting both genotyping and epidemiological data. We focus on spacer oligonucleotide typing (spoligotyping), a genotyping method based on analysis of a direct repeat (DR) locus. We use mixture models to identify strain families of MTC based on their spoligotyping patterns. Our algorithm, SPOTCLUST, incorporates biological information on spoligotype evolution, without attempting to derive the full phylogeny of MTC. We applied our algorithm to 535 different spoligotype patterns identified among 7166 MTC strains isolated between 1996 and 2004 from New York State TB patients. Two models were employed and validated: a 36-component model based on global spoligotype database SpolDB3, and a randomly initialized model (RIM) containing 48 components. Our analysis both confirmed previously expert-defined families of MTC strains and suggested certain new families. SPOTCLUST, which is available online, can be further improved by incorporating data obtained using additional strain genetic markers and epidemiological information. We demonstrate on New York City (NYC) patient data how the resulting models can potentially form the basis of TB control tools using genotyping.3

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Identification of novel intergenic repetitive units in a mycobacterial two‐component system operon

Cited by 199 publications

References 44 publications

Genetic diversity in the Mycobacterium tuberculosis complex based on variable numbers of tandem DNA repeats

Genetic diversity in the Mycobacterium tuberculosis complex based on variable numbers of tandem DNA repeats

Differential regulation of the two-component regulatory system senX3-regX3 in Mycobacterium tuberculosis

Identifying Mycobacterium tuberculosis complex strain families using spoligotypes

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