Intact<i>pks15/1</i>in Non–W-Beijing<i>Mycobacterium tuberculosis</i>Isolates

Chaiprasert, Angkana; Yorsangsukkamol, Jutaporn; Prammananan, Therdsak; Palittapongarnpim, Prasit; Leechawengwong, Manoon; Dhiraputra, Chertsak

doi:10.3201/eid1205.051208

Cited by 17 publications

(15 citation statements)

References 13 publications

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“…Hence, in this study, pks15/1 locus sequence differences did not correlate with mouse lung lesions and cannot explain the outbreak caused by PG004 in Contra Costa County. This finding is consistent with a recent report from Thailand that showed that an intact pks15/1 sequence is found among many non-Beijing family clinical M. tuberculosis strains isolated in similar proportions (.80 %) from patients with severe manifestations of tuberculosis such as tuberculosis meningitis, as well as from those with lung disease (Chaiprasert et al, 2006).…”

Section: Pks15/1 Gene Sequencesupporting

confidence: 92%

Community-wide transmission of a strain of Mycobacterium tuberculosis that causes reduced lung pathology in mice

Cantrell

Pascopella

Flood

et al. 2008

Journal of Medical Microbiology

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Since 1992, Mycobacterium tuberculosis strain PG004 has been responsible for a large outbreak of tuberculosis in one northern Californian community. There are no epidemiological or host factors to explain this outbreak. PG004 was therefore analysed for biological characteristics that might explain its widespread distribution. BABL/c mice were infected intravenously with PG004, non-PG004 M. tuberculosis strains CCC20 and CCC23 isolated from patients in the same community, and the laboratory strain H37Rv. The susceptibility of PG004 to reactive nitrogen intermediates (RNIs) was compared with that of H37Rv. Because of the reported association of phenolic glycolipid production with mouse virulence, a junction sequence in the polyketide synthase gene cluster (pks15/1) was compared among strains. It was found that the most virulent strain, based on mouse mortality, was not the outbreak strain PG004, but the non-outbreak strain CCC20. This strain had an intact pks15/1 sequence identical to that of another non-outbreak strain, CCC23, which caused death in only one out of ten mice in 300 days of follow-up. The outbreak strain PG004 had a frameshift mutation in the pks15/1 sequence identical to the sequence of H37Rv, and it was no more resistant to RNIs than H37Rv. The most distinguishing feature of PG004 was its failure to produce well-organized, coalescing granulomas in mouse lungs. The lack of organized granulomas and reduced pathology may prevent restriction of PG004 in the lungs and allow it to spread into alveolar air spaces and escape the host to transmit to others. Humans with reduced lung pathology may remain undiagnosed and untreated in the community longer than those with severe disease. The over-representation of an M. tuberculosis strain in a community, therefore, may be more associated with strains that cause reduced rather than severe lung pathology.

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Section: Pks15/1 Gene Sequencesupporting

confidence: 92%

Community-wide transmission of a strain of Mycobacterium tuberculosis that causes reduced lung pathology in mice

Cantrell

Pascopella

Flood

et al. 2008

Journal of Medical Microbiology

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“…Genetic markers considered to be specific for Beijing were later found in other non‐Beijing lineages. Such was the case of pks 15‐1, which was initially considered to be intact only in Beijing isolates [20,21], but was later identified in non‐Beijing lineages (EIA and CAS) [25,32]. We evaluated a selection of non‐Beijing strains belonging to these lineages in our PCR‐HRM assay and they all behaved as non‐Beijing isolates, thus confirming the exclusiveness of A191C for the Beijing genotype.…”

Section: Discussionmentioning

confidence: 59%

“…However, no specific patterns have been proposed as markers to successfully identify Beijing strains [30,31]. Recently, an intact open reading frame in the pks15/1 gene [20] was proposed as a specific marker for the Beijing lineage, although this was later identified in other non‐Beijing lineages [25,32]. The most efficient marker for identification of the Beijing genotype could be the RD105 deletion [21], and it only requires specific PCR and electrophoretic analysis, which makes this option a good alternative for laboratories lacking advanced equipment.…”

Section: Discussionmentioning

confidence: 99%

A novel method for the rapid and prospective identification of Beijing Mycobacterium tuberculosis strains by high-resolution melting analysis

Alonso

Navarro

Barletta

et al. 2011

Clinical Microbiology and Infection

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Genotypic analysis of Mycobacterium tuberculosis (MTB) has enabled the definition of several lineages. The Beijing family, which is considered highly virulent and transmissible, has been associated with resistance in certain settings and involved in severe outbreaks, making it one of the most closely-monitored lineages. Therefore, rapid prospective identification of Beijing MTB strains could be relevant. In the present study, we evaluate a real-time PCR followed by high-resolution melting (HRM) based on the identification of a single nucleotide polymorphism (SNP) in the Rv2629 gene which defines Beijing lineage (A191C for Beijing genotype and A191A for non-Beijing genotype). This combined methodology efficiently differentiated Beijing and non-Beijing strains in 100% of the isolates from a collection of reference strains without requiring specific DNA probes. Additionally, HRM was able to assign a Beijing/non-Beijing genotype in 90.9% of the respiratory specimens assayed. Its applicability was tested on a Peruvian sample of circulating MTB strains, in which it identified 10.7% as belonging to the Beijing genotype; this proportion reached 20% in the North Lima area. HRM analysis of the A191C SNP is a rapid, reliable, and sensitive method for the efficient prospective survey of high-risk Beijing MTB strains, even in developing settings where MTB culture is often not available.

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“…Upon evaluation of RD105, RD142, RD150 and RD181, we observed that all strains had deleted RD105 and RD181 and intact RD142 and RD150, except for two strains from Mozambique (strains 186 and 198) that had RD150 deleted. This means that all Brazilian strains and 87.5% of the strains from Mozambique presented sublineage type 3; and 12.5% of the Mozambican strains belonged to type 4 sublineage, according to the classification proposed by Reed et al [10].…”

Section: Resultsmentioning

confidence: 89%

“…Deletion of the RD207 defines the sublineage 2 and with additional deletion of RD181 is the basis of sublineage 3, which further evolved to sublineages 4 and 5 by deletion of RD150 and RD142, respectively. Related studies show that all the MtbB strains, in contrast to many other Mtb genotype lineages, possess intact pks15/1 gene, involved in the synthesis of phenolglycolipids, PGL, that is one of the mycobacterial virulence factors [10]. However, recent study demonstrated that the Beijing strains of sublineages 3, 4 and 5, but not those of the sublineages 1 and 2, are able to produce these antigens, suggesting that this biological property was acquired by MtbB during evolution [11].…”

Section: Introductionmentioning

confidence: 99%

Genetic diversity of the Mycobacterium tuberculosis Beijing family in Brazil and Mozambique and relation with infectivity and induction of necrosis in THP-1 cells

Gomes¹,

Vasconcellos²,

Gomes³

et al. 2015

Tuberculosis

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Intactpks15/1in Non–W-BeijingMycobacterium tuberculosisIsolates

Cited by 17 publications

References 13 publications

Community-wide transmission of a strain of Mycobacterium tuberculosis that causes reduced lung pathology in mice

Community-wide transmission of a strain of Mycobacterium tuberculosis that causes reduced lung pathology in mice

A novel method for the rapid and prospective identification of Beijing Mycobacterium tuberculosis strains by high-resolution melting analysis

Genetic diversity of the Mycobacterium tuberculosis Beijing family in Brazil and Mozambique and relation with infectivity and induction of necrosis in THP-1 cells

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