A deletion defining a common Asian lineage of<i>Mycobacterium tuberculosis</i>associates with immune subversion

Newton, Sandra M.; Smith, Rebecca J.; Wilkinson, Katalin A.; Nicol, Mark P.; Garton, Natalie J.; Staples, Karl J.; Stewart, Graham R.; Wain, John; Martineau, Adrian R.; Fandrich, Sarah Elizabeth; Smallie, Tim; Foxwell, Brian M. J.; Al-Obaidi, Ahmed Saleh R.; Shafi, Jamila; Rajakumar, Kumar; Kampmann, Beate; Andrew, Peter W.; Ziegler-Heitbrock, Loems; Barer, Michael R.; Wilkinson, Robert J.

doi:10.1073/pnas.0604283103

Cited by 102 publications

(90 citation statements)

References 25 publications

(28 reference statements)

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“…Importantly, LSPs in certain M. tuberculosis strains have been linked to host immune modification. In particular, Central Asian (CAS) strains possess an LSP that has been associated with an increased capacity to promote host IL-10 production as an immune evasion strategy (39). Although RD Rio strains have lost a phenoglycolipid involved in inhibiting proinflammatory cytokines due to a deletion within the pks15/1 gene, we speculate that RD Rio M. tuberculosis may dampen immune recognition through the deletion of two of its surface antigens (PPE55 and PPE56), among other potential mechanisms.…”

Section: Discussionmentioning

confidence: 99%

RD ^Rio Mycobacterium tuberculosis Infection Is Associated with a Higher Frequency of Cavitary Pulmonary Disease

Lazzarini

Spindola

Bang³

et al. 2008

J Clin Microbiol

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Molecular genotyping has shown Mycobacterium tuberculosis lineages to be geographically restricted and associated with distinct ethnic populations. Whether tuberculosis (TB) caused by some M. tuberculosis lineages can present with a differential clinical spectrum is controversial because of very limited clinical data. We recently reported on the discovery of RD Rio M. tuberculosis, a Latin American-Mediterranean sublineage that is the predominant cause of TB in Rio de Janeiro, Brazil. To investigate the clinical attributes of TB caused by RD Rio strains, we studied a cohort of TB cases from Belo Horizonte, Brazil, in which clinical information recorded on a standardized questionnaire was collected at the time of microbiological testing. These patients were referred for culture and drug susceptibility testing because of the clinical suspicion of "complicated" TB, as demonstrated by high rates of multidrug resistance (12%) and cavitary TB (80%). We performed spoligotyping and RD Rio genotyping on the M. tuberculosis strains and analyzed the clinical data from these patients. RD Rio M. tuberculosis accounted for 37% of the total TB burden. Multivariate analysis found a significant association between TB caused by RD Rio strains and pulmonary cavitation and residence in Belo Horizonte. Since cavitary TB is associated with higher sputum bacillary load, our findings support the hypothesis that RD Rio M. tuberculosis is associated with a more "severe" disease as a strategy to increase transmission. Future studies are needed to confirm these observations and to better define the contribution of RD Rio M. tuberculosis to the global TB epidemic.Mycobacterium tuberculosis, the etiologic agent of tuberculosis (TB), is estimated to have infected one-third of the world's population and annually causes ϳ8 million new TB cases and Ͼ2 million deaths (16, 58). The challenges posed by TB have been further worsened by the emergence of multi-drugresistant and extensively drug-resistant M. tuberculosis strains.Molecular typing, based on genetic markers, permits the rapid detection and species level identification of mycobacteria within the M. tuberculosis complex (MTC), as well as provides useful tools for examining the transmission and evolution of these microorganisms (7,17,30,53). Genome-wide single nucleotide polymorphism (SNP) and deletion analyses have been used to organize the global M. tuberculosis population structure into overlapping phylogenies with major lineages that show distinct geographic distribution and that may be associated with specific host adaptation (1,21,23,24,27,28,50). Similar results have also been obtained with spoligotyping and IS6110-RFLP fingerprint analysis (18). The W/Beijing lineage, for example, is the predominant family in major SNP cluster II, accounts for ϳ10% of strains causing TB globally, and is localized mainly to Asia but has spread internationally. W/Beijing has been associated with outbreaks and multiple drug resistance (MDR) (4, 32) and also contributed significantly to the resurgence of...

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Section: Discussionmentioning

confidence: 99%

RD ^Rio Mycobacterium tuberculosis Infection Is Associated with a Higher Frequency of Cavitary Pulmonary Disease

Lazzarini

Spindola

Bang³

et al. 2008

J Clin Microbiol

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“…It has been shown that strains with the RD750 deletion are a prominent cause of tuberculosis among Asians in the United Kingdom and in the Indian subcontinent. The RD750 deletion appears to have increased, rather than decreased, the capacity of this lineage of MTB to cause immune deviation and contribute to its persistence and outbreak potential in human populations [13]. It has been suggested that deletions in the RD149 and RD152 regions may be due to transposition and homologous recombination events between adjacent IS6110 fragments.…”

Section: Spoligotypesmentioning

confidence: 99%

“…These deletions affect the Rv1519 and Rv1520 genes which have been shown to up-regulate the anti-inflammatory cytokine IL-10 in the human monocyte derived macrophages; thus the deletions appear to favor the intracellular survival of the pathogen [13].…”

Section: Introductionmentioning

confidence: 99%

Occurrence of RD149 and RD152 deletions in Mycobacterium tuberculosis strains from Pakistan

Kanji

Hasan

Tanveer

et al. 2011

J Infect Dev Ctries

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Introduction: Central Asian Strain 1 (CAS1) is the predominant Mycobacterium tuberculosis genotype in Pakistan. The occurrence of deletions in regions of differences (RDs) among CAS1 and other predominant genogroups in the country were investigated. Methodology: Using stratified random sampling, 235 M. tuberculosis (185 pulmonary; 50 extrapulmonary) strains were selected from 926 previously spoligotyped isolates, including 171 CAS strains (133 CAS1 (ST26), 38 CAS subfamily), 8 Beijing isolates, 47 isolates belonging to other previously defined ("Other") clusters, and 9 previously undefined Unique isolates. Commonly reported RD deletions, RD1, RD750, RD207, RD149, RD152, RD105, RD150, RD142 and RD181, were investigated using a PCR-based method. Results: Deletions in RDs 750, 149 and 152 were identified among CAS strains, and in RDs 207, 149, 152, 105, 150, 142 and 181 in Beijing isolates. CAS1 strains showed more frequent RD149 deletions compared with CAS subfamily strains (p=0.036), and more frequent RD152 deletions compared with "Other" clusters (p=0.003). RD149 and RD152 deletions were more frequent in Beijing isolates compared with CAS1 strains (p < 0.001). Concurrent RD149 and RD152 deletions were more frequent in CAS1 compared with "Other" clusters (p < 0.001) and in Beijing strains compared with CAS1 (p < 0.001). No significant difference was detected in RD deletion patterns between pulmonary and extra pulmonary isolates. Conclusion: Higher frequencies of RD149 and RD152 deletions and of concurrent RD149 and RD152 deletions were found in CAS1 and Beijing strains compared with CAS subfamilies, "Other" clusters and Unique strains. No association between these deletions and disease presentation, pulmonary or extrapulmonary tuberculosis, was observed.

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“…All cells were cultured in triplicate in 100 ml RPMI enriched with 10% heat-inactivated fetal calf serum (GIBCO, Mowbray, South Africa) and 100 U/ml penicillin G (Merck, Modderfontein, South Africa) in 96-well plates. The M. tuberculosis strain H37Rv was prepared as previously described (30) and cells were infected at a multiplicity of infection of 1:1. A new vial was thawed for every experiment.…”

Section: Infection Assay Of Monocytes and Alveolar Macrophages With Mmentioning

confidence: 99%

HIV-1 Infection Impairs the Bronchoalveolar T-Cell Response to Mycobacteria

Kalsdorf¹,

Scriba²,

Wood³

et al. 2009

Am J Respir Crit Care Med

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

Cited by 102 publications

References 25 publications

RD ^Rio Mycobacterium tuberculosis Infection Is Associated with a Higher Frequency of Cavitary Pulmonary Disease

RD ^Rio Mycobacterium tuberculosis Infection Is Associated with a Higher Frequency of Cavitary Pulmonary Disease

Occurrence of RD149 and RD152 deletions in Mycobacterium tuberculosis strains from Pakistan

HIV-1 Infection Impairs the Bronchoalveolar T-Cell Response to Mycobacteria

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

Cited by 102 publications

References 25 publications

RD Rio Mycobacterium tuberculosis Infection Is Associated with a Higher Frequency of Cavitary Pulmonary Disease

RD Rio Mycobacterium tuberculosis Infection Is Associated with a Higher Frequency of Cavitary Pulmonary Disease

Occurrence of RD149 and RD152 deletions in Mycobacterium tuberculosis strains from Pakistan

HIV-1 Infection Impairs the Bronchoalveolar T-Cell Response to Mycobacteria

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Product

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RD ^Rio Mycobacterium tuberculosis Infection Is Associated with a Higher Frequency of Cavitary Pulmonary Disease

RD ^Rio Mycobacterium tuberculosis Infection Is Associated with a Higher Frequency of Cavitary Pulmonary Disease