The Pathogenesis and Fate of Tubercle Produced by Dissociated Variants of Tubercle Bacilli

Oatway, William H.; Steenken, William

doi:10.1093/infdis/59.3.306

Cited by 21 publications

(8 citation statements)

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“…The mycobacterial strains used were Mycobacterium smegmatis mc 2 155, 42 M. tuberculosis wild-type strain H37Rv 31 sigG mutant strains in H37Rv Δ sigG 1 and Δ sigG 2, 39 and a sigG operon deletion in H37Rv Δ sigG WO (this study). Mycobacterial cultures grown in Dubos medium (Difco) supplemented with albumin and 0.2% glycerol or on Difco Middlebrook 7H11 agar plates (Beckton Dickenson) supplemented with 4% albumin and 0.5% glycerol.…”

Section: Methodsmentioning

confidence: 99%

Characterisation of the Mycobacterium tuberculosis alternative sigma factor SigG: Its operon and regulon

Gaudion¹,

Dawson²,

Davis³

et al. 2013

Tuberculosis

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SummaryA major step in the pathogenesis of Mycobacterium tuberculosis is the ability to survive inside macrophages, where it is exposed to a number of DNA damaging agents. The alternative sigma factor SigG has been shown to be upregulated by DNA damaging agents and by macrophage infection, but not to regulate genes of the DNA repair pathway. Here we show that SigG is expressed from at least two promoters, the most dominant of these being the DNA damage inducible RecA_Ndp promoter. This promoter is located within the annotated coding region of SigG and so the correct translational start site was determined experimentally and found to be 114 bp downstream of the annotated start site. Examining the gene expression profile of a SigG over-expression strain found a small number of genes to up-regulated, two of these encoded proteins containing glyoxylase-like domains.

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Section: Methodsmentioning

confidence: 99%

Characterisation of the Mycobacterium tuberculosis alternative sigma factor SigG: Its operon and regulon

Gaudion¹,

Dawson²,

Davis³

et al. 2013

Tuberculosis

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“…The bacterial model applied in this study is that of M. tuberculosis H37Ra and H37Rv, sibling strains derived from the parental H37 (Oatway & Steenken, 1936;Steenken et al, 1934), a laboratory strain originally isolated from the sputum of a pulmonary TB patient in 1906 (Steenken & Gardner, 1946). Strains H37Ra and H37Rv are highly similar, as studies have shown little genomic difference between them (Bhargava et al, 1990;Collins & De Lisle, 1984;Imaeda, 1985), save for the RvD2 region of difference (Brosch et al, 1999;Lari et al, 2001), which has not been conclusively linked to pathogenesis .…”

Section: Introductionmentioning

confidence: 99%

Characterization of genes differentially expressed within macrophages by virulent and attenuated Mycobacterium tuberculosis identifies candidate genes involved in intracellular growth

Lam

Stokes

2008

Microbiology

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To identify genes involved in the intracellular survival of Mycobacterium tuberculosis we compared the transcriptomes of virulent (H37Rv) and attenuated (H37Ra) strains during their interaction with murine bone-marrow-derived macrophages. Expression profiling was accomplished via the bacterial artificial chromosome fingerprint array (BACFA) technique. Genes identified with BACFA, and confirmed via qPCR to be upregulated in the attenuated H37Ra at 168 h postinfection, were frdB, frdC and frdD. Genes upregulated in the virulent H37Rv were pks2, aceE and Rv1571. Further qPCR analysis of these genes at 4 and 96 h post-infection revealed that the frd operon (encoding the fumarate reductase enzyme complex) is expressed at higher levels in the virulent H37Rv at earlier time points while the expression of aceE and pks2 is higher in the virulent strain throughout the course of infection. Assessment of frd transcripts in oxygen-limited cultures of M. tuberculosis H37Ra and H37Rv showed that the attenuated strain displayed a lag in frdA and frdB expression at the onset of microaerophilic culture, when compared to microaerophilic cultures of H37Rv and aerated cultures of H37Ra. Lastly, treatment of intracellular bacteria with a putative inhibitor of fumarate reductase resulted in a significant reduction of bacterial growth.

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“…A strategy to identify virulence determinants by genetic complementation requires (i) two strains that are genetically similar, (ii) a phenotype associated with virulence, and (iii) gene transfer systems. An existing pair of M. tuberculosis strains, H37Rv (virulent) and H37Ra (avirulent), distinguishable by their ability to cause disease in animal models (17), was used. H37Ra and H37Rv were derived from the same clinical isolate in 1934 (17,21), and pulsed-field gel analyses of DNA fragments generated by digestion with infrequently cutting enzymes revealed that their macroscopic genome organizations are similar (1).…”

mentioning

confidence: 99%

“…An existing pair of M. tuberculosis strains, H37Rv (virulent) and H37Ra (avirulent), distinguishable by their ability to cause disease in animal models (17), was used. H37Ra and H37Rv were derived from the same clinical isolate in 1934 (17,21), and pulsed-field gel analyses of DNA fragments generated by digestion with infrequently cutting enzymes revealed that their macroscopic genome organizations are similar (1). Previous studies of H37Ra and H37Rv pathogenicity (4,15,16,19) demonstrated the correlation of the extent of disease in animal models to the extent of multiplication in mouse spleen and lung tissue.…”

mentioning

confidence: 99%

Use of in vivo complementation in Mycobacterium tuberculosis to identify a genomic fragment associated with virulence

et al. 1994

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Novel molecular tools and genetic methods were developed to isolate genomic fragments of Mycobacterium tuberculosis that may be associated with virulence. We sought to restore virulence, a characteristic of M. tuberculosis that is correlated with growth rate in mouse spleen and lung tissue, to the avirulent strain H37Ra by complementation. A representative library of the virulent M. tuberculosis strain H37Rv was constructed and transformed into H37Ra. Enrichment for individual faster-growing recombinants was achieved by passage of pools of H37Ra transformants harboring the H37Rv library through mice. A molecular strategy was devised to isolate and clone the H37Rv genomic DNA fragment ivg, which conferred a more rapid in vivo growth rate to H37Ra.Tuberculosis is a worldwide health problem that causes approximately 3 million deaths each year (13); however, little is known about the molecular basis of the pathogenesis of tuberculosis. The disease is caused by infection with Mycobacterium tuberculosis; tubercle bacilli are inhaled and then ingested by alveolar macrophages. As is the case with most pathogens, infection with M. tuberculosis does not always result in disease. The infection is often arrested by a developing cell-mediated immunity resulting in the formation of microscopic lesions, or tubercles, in the lung. If cell-mediated immunity does not limit the spread of M. tuberculosis, caseous necrosis, bronchial wall erosion, and pulmonary cavitation may occur (5). The factors that determine whether infection with M. tuberculosis results in disease are incompletely understood.The ability to transfer and express recombinant DNA among the mycobacteria, which has been recently demonstrated (11,20), enables the usage of molecular genetics to elucidate pathogenic mechanisms. However, the present lack of evidence of homologous recombination in the pathogenic mycobacteria prevents the application of allele exchange systems (12). We sought to develop an in vivo genetic complementation system that utilizes integrating shuttle cosmid libraries to identify potential virulence genes of M. tuberculosis. One of the first examples of in vivo selection for virulent bacteria was demonstrated by the classic work of Griffith in 1928 (7). Griffith observed that as a result of genetic exchange between bacteria, virulent, capsulated pneumococci were recovered from mice infected with a mixture of live attenuated, noncap-* Corresponding author. Mailing address: § Present address: PathoGenesis Corporation, Seattle, WA 98119. sulated pneumococci and heat-killed capsulated pneumococci (7).A strategy to identify virulence determinants by genetic complementation requires (i) two strains that are genetically similar, (ii) a phenotype associated with virulence, and (iii) gene transfer systems. An existing pair of M. tuberculosis strains, H37Rv (virulent) and H37Ra (avirulent), distinguishable by their ability to cause disease in animal models (17), was used. H37Ra and H37Rv were derived from the same clinical isolate in 1934 (17,21), and puls...

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The Pathogenesis and Fate of Tubercle Produced by Dissociated Variants of Tubercle Bacilli

Cited by 21 publications

References 0 publications

Characterisation of the Mycobacterium tuberculosis alternative sigma factor SigG: Its operon and regulon

Characterisation of the Mycobacterium tuberculosis alternative sigma factor SigG: Its operon and regulon

Characterization of genes differentially expressed within macrophages by virulent and attenuated Mycobacterium tuberculosis identifies candidate genes involved in intracellular growth

Use of in vivo complementation in Mycobacterium tuberculosis to identify a genomic fragment associated with virulence

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