Predominant VNTR family of strains of <i>Mycobacterium tuberculosis</i> isolated from South Asian patients

Gascoyne-Binzi, Deborah; Barlow, Rachael; Essex, Anthony; Gelletlie, Ruth; Khan, Mumtaz Ali; Hafiz, S; Collyns, Timothy; Frizzell, R. A.; Hawkey, Peter M.

doi:10.5588/09640569512995

Cited by 19 publications

(17 citation statements)

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“…This large sequence polymorphism has recently been designated RD750, a relatively ancient single polymorphism that defines the East African-Indian lineage (also known as Delhi, CAS, or South Asian lineage) (3). These strains are a prominent cause of tuberculosis amongst Asians in the U.K. (Ϸ40% in Leicester; H. Patel, personal communication) and in the Indian subcontinent (21).…”

Section: Resultsmentioning

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.

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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Section: Resultsmentioning

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.

102

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“…There is already evidence of the emergence of a dominant VNTR type, which possesses the fivelocus profile 42235, among isolates derived from patients in the cities of Leeds and Bradford in the United Kingdom. Isolates with this profile accounted for 23% of the 210 isolates investigated and was exclusively associated with patients with South Asian surnames (13). Remarkably, a further 27% of isolates differed from the isolates with the VNTR profile associated with patients with a South Asian surname at only one of five loci (13).…”

Section: Discussionmentioning

confidence: 99%

“…Isolates with this profile accounted for 23% of the 210 isolates investigated and was exclusively associated with patients with South Asian surnames (13). Remarkably, a further 27% of isolates differed from the isolates with the VNTR profile associated with patients with a South Asian surname at only one of five loci (13). Indeed, isolate CH, the 12 acute-phase secondary isolates, and the 2 outbreak-associated isolates identified during prospective surveillance were all found to share this same VNTR profile, profile 42235 (Monk, unpublished).…”

Section: Discussionmentioning

confidence: 99%

Use of Genome Level-Informed PCR as a New Investigational Approach for Analysis of Outbreak-Associated Mycobacterium tuberculosis Isolates

et al. 2004

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Mycobacterium tuberculosis strain CH, the index isolate linked to a major tuberculosis outbreak associated with high levels of transmissibility and virulence, was characterized by microarray analysis by use of a PCR product array representative of the genome of M. tuberculosis strain H37Rv. Seven potential genomic deletions were identified in CH, five of which were confirmed by PCR analysis across the predicted deletion points. The panel of five PCRs required to individually interrogate these loci was collectively referred to as the genome level-informed PCR (GLIP) assay. GLIP analysis was performed with CH, 12 other epidemiologically linked isolates, and 43 recent, non-outbreak-associated isolates derived from patients within the local area. All 13 outbreak-linked isolates showed a profile corresponding to the presence of all five deletions. These 13 isolates were also found to share common variable-number tandem repeat and mycobacterial interspersed repetitive unit profiles. None of the 43 non-outbreak-associated isolates exhibited the five-deletion profile. Although three individual deletions were present in upwards of 44% of the non-outbreak-associated isolates, no single-deletion isolates were detected. Interestingly, none of these deletions had been previously recognized, and sequence analysis of the immediate flanking regions in CH failed to identify a likely mechanism of deletion for four of the five loci. The GLIP assay also proved valuable in ongoing surveillance of the outbreak, rapidly identifying a further two outbreak-associated cases months after the initial cluster and, importantly, dismissing a further 12 epidemiologically suspect cases, which allowed the optimum deployment of public health resources.Mycobacterium tuberculosis remains a major killer, accounting for more than 2 million deaths annually. Its success as a pathogen is highlighted by its remarkable ability to spread among human populations. It is estimated that more than 2 billion people, a third of the world's population, are infected with this bacterium (29). The major burden is borne by underdeveloped nations. However, even in settings with excellent public health and clinical facilities, sporadic outbreaks of tuberculosis remain a continuing threat (7,23).In 2001 the largest recognized outbreak of tuberculosis in a United Kingdom school was detected in Leicester. The index patient was a 14-year-old student who had been complaining of a chronic cough for 9 months prior to being diagnosed with sputum smear-positive cavitary pulmonary tuberculosis (9). Subsequent screening and investigation by the health authority of the entire school population led to the diagnosis of a further 77 cases of active disease and 254 cases of latent tuberculosis among students, staff, and family contacts of the index patient and secondary cases. This outbreak occurred in Leicester, a city with rates of tuberculosis exceeding four times the national average (24; P. Monk, unpublished data). Given the large scale of the outbreak and the elevated rates of tu...

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“…Besides these types, it is worth mentioning the following families detected in the region: (i) the Mycobacterium africanum family, reported, to our knowledge, for the first time in Italy, including five isolates which lacked spacers 8, 9, and 39 and which were isolated from patients who were born in Senegal and had emigrated to Italy in 2001 to 2002 (the isolates belonged to genotypic group 1 and showed basically the same IS6110 RFLP profiles-one had an extra band; four shared spoligotype profile ST181, characterized by the absence of spacers 7 to 9 and 39; and the fifth one had an orphan profile characterized by the absence of spacers 7 to 9, 12, 19, 20, and 39); (ii) the Mycobacterium bovis family (ST482), including three isolates which had a single IS6110 insertion, which belonged to genotypic group 1, and which were isolated from Italian-born patients in three distinct city hospitals; (iii) the central Asia 1 (CAS1) family (ST25 and ST26), which was characterized by the absence of spacers 4 to 7 and 23 to 34 and, in IS6110 fingerprinting, by two high-molecular-weight bands at 12.1 and 10.1 kb and which was present in India, Pakistan, Sudan, and elsewhere (7,19,25); (iv) the East African-Indian 2 (EAI2/Manila) family (ST19) (3); and (v) the Cameroun family (ST61), including four isolates, all from African-born patients (16).…”

Section: Resultsmentioning

confidence: 99%

Genetic Diversity, Determined on the Basis of katG463 and gyrA95 Polymorphisms, Spoligotyping, and IS 6110 Typing, of Mycobacterium tuberculosis Complex Isolates from Italy

et al. 2005

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Mycobacterium tuberculosis complex isolates (n ‫؍‬ 248) collected during a 1-year period in Tuscany, Italy, were genotyped for the katG463 and gyrA95 polymorphisms and by standard spacer oligonucleotide typing (spoligotyping) and IS6110 restriction fragment length polymorphism (RFLP) assays. Most of the isolates (n ‫؍‬ 212; 85.5%) belonged to genotypic groups 2 and 3, which included most isolates from Italian-born patients. The remaining isolates were genotypic group 1 organisms, which were prevalent among foreign-born patients (29 of 36; 80.6%). Spoligotype analysis detected 116 unique patterns and 34 clusters including 166 isolates. The combination of spoligotyping and IS6110 RFLP analyses yielded 28 distinct clusters including 65 identical isolates (26.2%)-22 clusters with 2 isolates, 4 clusters with 3 isolates, 1 cluster with 4 isolates, and 1 cluster with 5 isolates-thus proving a low transmission rate in the community. Predominant spoligotypes representing 50% of clustered isolates were found in six clusters that included widespread type ST53 (clade T1) with 29 isolates (11.7% of total isolates); types ST50 and ST47 (Haarlem family) with 18 isolates (7.3%) and 8 isolates (3.2%), respectively; type ST42 (Latino-American and Mediterranean clade) with 13 isolates (5.2%); new type ST1737 (named "Tuscany") with 8 isolates (3.2%); and type ST1 (W-Beijing family) with 7 isolates (2.8%). Other spoligotype families, such as the Mycobacterium africanum, East African-Indian (EAI2/Manila), and central Asia 1 (CAS1/Delhi) families (all including organisms of genotypic group 1) and the Cameroun family (genotypic group 2), were detected especially among immigrant patients. The occurrence of genotypes originally found in distant geographic areas with a high prevalence of tuberculosis may represent a hallmark for changes in the dynamics of transmission of tuberculosis in the region in the near future.Since the discovery of polymorphic DNA in Mycobacterium tuberculosis, molecular typing of strains has become a valuable tool in the study of the epidemiology of tuberculosis (TB) by allowing investigators to track epidemics, detect new outbreaks, and achieve better knowledge of moving and expanding strains (1).Analysis of restriction fragment length polymorphisms (RFLPs), based on the variability of the chromosomal location and copy number of insertion sequence IS6110, is considered the standard approach for the genotyping of M. tuberculosis isolates and has allowed the construction of large databases of IS6110-based genotypes (24). IS6110 fingerprinting has been shown to have great potential for the clonal differentiation of M. tuberculosis isolates (11); however, IS6110 RFLP analysis is a labor-intensive and time-consuming methodology, and its use is hampered for strains with fewer than six IS6110 insertions that have a limited degree of IS6110 polymorphisms or when rapid results are needed, such as in cases of nosocomial transmission of TB or laboratory cross-contaminations. In this context, PCR-based spacer oligonucleotide...

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Predominant VNTR family of strains of Mycobacterium tuberculosis isolated from South Asian patients

Abstract: The VNTR profile 42235 may represent a family of strains commonly found in communities associated with South Asia.

Cited by 19 publications

References 0 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

Use of Genome Level-Informed PCR as a New Investigational Approach for Analysis of Outbreak-Associated Mycobacterium tuberculosis Isolates

Genetic Diversity, Determined on the Basis of katG463 and gyrA95 Polymorphisms, Spoligotyping, and IS 6110 Typing, of Mycobacterium tuberculosis Complex Isolates from Italy

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