The genetic portrait of an outbreak strain

Yeşilkaya, Hasan; Forbes, Ken J.; Shafi, Jamila; Smith, Rebecca J.; Dale, Jeremy W.; Rajakumar, Kumar; Barer, Michael R.; Andrew, Peter W.

doi:10.1016/j.tube.2005.08.019

Cited by 8 publications

(10 citation statements)

References 33 publications

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“…In 2001, a large school-associated outbreak of tuberculosis occurred in Leicester, U.K., and both the genotype of the outbreak strain, CH, and the acquired immune responses of the exposed schoolchildren were characterized in unusual detail (10)(11)(12). CH was transmitted extensively from a single index case, leading to 254 cases of latent infection by tuberculin skin testing (TST) amongst 1,128 other pupils tested.…”

mentioning

confidence: 99%

A deletion defining a common Asian lineage ofMycobacterium tuberculosisassociates with immune subversion

Newton

Smith

Wilkinson

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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102

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Six major lineages of Mycobacterium tuberculosis appear preferentially transmitted amongst distinct ethnic groups. We identified a deletion affecting Rv1519 in CH, a strain isolated from a large outbreak in Leicester U.K., that coincidentally defines the East African-Indian lineage matching a major ethnic group in this city. In broth media, CH grew less rapidly and was less acidic and H 2 O 2 -tolerant than reference sequenced strains (CDC1551 and H37Rv). Nevertheless, CH was not impaired in its ability to grow in human monocyte-derived macrophages. When compared with CDC1551 and H37Rv, CH induced less protective IL-12p40 and more antiinflammatory IL-10 and IL-6 gene transcription and secretion from monocyte-derived macrophages. It thus appears that CH compensates microbiological attenuation by skewing the innate response toward phagocyte deactivation. Complementation of Rv1519 , but none of nine additional genes absent from CH compared with the type strain, H37Rv, reversed the capacity of CH to elicit antiinflammatory IL-10 production by macrophages. The Rv1519 polymorphism in M. tuberculosis confers an immune subverting phenotype that contributes to the persistence and outbreak potential of this lineage.

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mentioning

confidence: 99%

A deletion defining a common Asian lineage ofMycobacterium tuberculosisassociates with immune subversion

Newton

Smith

Wilkinson

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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102

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“…A comparative genomics study of a panel of 19 clinically and epidemiologically characterized isolates of Mtb found that those with greater genome deletions caused significantly less pulmonary cavitation suggesting that pathogenicity is linked to bacterial factors [59]. That bacterial genotype contributes to the transmission phenotype of the host is also indicated by the finding that a large sequence polymorphism in a gene encoding molybdopterin oxyreductase was associated with clustering [60] and an Mtb strain associated with a large outbreak in the UK harbored an insertion in an intergeneic region Rv2815-2816c [61]. Whole genome sequencing and evolutionary convergence analysis of 100 strains either least or most likely to be transmitted revealed that five Mtb genes were shared by the transmissible strains.…”

Section: Discussionmentioning

confidence: 99%

Transmission phenotype of Mycobacterium tuberculosis strains is mechanistically linked to induction of distinct pulmonary pathology

et al. 2019

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In a study of household contacts (HHC), households were categorized into High (HT) and Low (LT) transmission groups based on the proportion of HHC with a positive tuberculin skin test. The Mycobacterium tuberculosis (Mtb) strains from HT and LT index cases of the households were designated Mtb-HT and Mtb-LT, respectively. We found that C3HeB/FeJ mice infected with Mtb-LT strains exhibited significantly higher bacterial burden compared to Mtb-HT strains and also developed diffused inflammatory lung pathology. In stark contrast, a significant number of mice infected with Mtb-HT strains developed caseating granulomas, a lesion type with high potential to cavitate. None of the Mtb-HT infected animals developed diffused inflammatory lung pathology. A link was observed between increased in vitro replication of Mtb-LT strains and their ability to induce significantly high lipid droplet formation in macrophages. These results support that distinct early interactions of Mtb-HT and Mtb-LT strains with macrophages and subsequent differential trajectories in pathological disease may be the mechanism underlying their transmission potential.

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“…First-strand cDNA synthesis was performed on approximately 1 μg DNase-treated total RNA, immediately after isolation, using 200 U SuperScript II reverse transcriptase (Invitrogen) and random hexamers at 42 °C for 55 min (Yesilkaya et al , 2006). cDNA (15 ng) was amplified in a 20 μl reaction volume that contained 1× SYBR Green PCR master mix (Applied Biosystems) and 3 pmol of each primer (Table 1).…”

Section: Methodsmentioning

confidence: 99%

The pneumococcal response to oxidative stress includes a role for Rgg

et al. 2009

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Streptococcus pneumoniae resides in the oxygen-rich environment of the upper respiratory tract, and therefore the ability to survive in the presence of oxygen is an important aspect of its in vivo survival. To investigate how S. pneumoniae adapts to oxygen, we determined the global gene expression profile of the micro-organism in aerobiosis and anaerobiosis. It was found that exposure to aerobiosis elevated the expression of 54 genes, while the expression of 15 genes was downregulated. Notably there were significant changes in putative genome plasticity and hypothetical genes. In addition, increased expression of rgg, a putative transcriptional regulator, was detected. To test the role of Rgg in the pneumococcal oxidative stress response, an isogenic mutant was constructed. It was found that the mutant was sensitive to oxygen and paraquat, but not to H2O2. In addition, the absence of Rgg strongly reduced the biofilm-forming ability of an unencapsulated pneumococcus. Virulence studies showed that the median survival time of mice infected intranasally with the rgg mutant was significantly longer than that of the wild-type-infected group, and the animals infected with the mutant developed septicaemia later than those infected intranasally with the wild-type.

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The genetic portrait of an outbreak strain

Cited by 8 publications

References 33 publications

A deletion defining a common Asian lineage ofMycobacterium tuberculosisassociates with immune subversion

A deletion defining a common Asian lineage ofMycobacterium tuberculosisassociates with immune subversion

Transmission phenotype of Mycobacterium tuberculosis strains is mechanistically linked to induction of distinct pulmonary pathology

The pneumococcal response to oxidative stress includes a role for Rgg

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