Global Study of IS
            <i>6110</i>
            in a Successful Mycobacterium tuberculosis Strain: Clues for Deciphering Its Behavior and for Its Rapid Detection

Millán-Lou, María Isabel; López-Calleja, Ana Isabel; Colmenarejo, Cristina; Lezcano, María Antonia; Vitoria, María Asunción; Portillo, Patricia Del; Otal, Isabel; Martı́n, Carlos; Samper, Sofía

doi:10.1128/jcm.00970-13

Cited by 18 publications

(16 citation statements)

References 49 publications

(59 reference statements)

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“…In variant 7, 10 of the 12 IS6110 insertion sites known for M. tuberculosis Zaragoza were confirmed by PCR (13). However, the two nonamplified copies were located a relatively small distance from each other (9,860 bp for the H37Rv reference strain).…”

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confidence: 86%

“…The M. tuberculosis Zaragoza strain spread in Zaragoza, Spain, and reached 18.7% of all isolates of M. tuberculosis in 2001 to 2004 (11). This strain was classified in principal genetic group 3 and in singlenucleotide polymorphism (SNP) cluster group 6a (12), it demonstrated the rare spoligotype SIT773, and it carried 12 localized copies of IS6110 (13). In addition, in the context of a highthroughput survey of in vivo IS6110 transposition in multiple M. tuberculosis genomes, an additional IS6110 copy was detected in the oriC region in one isolate (14).…”

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confidence: 98%

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In Vivo IS 6110 Profile Changes in a Mycobacterium tuberculosis Strain as Determined by Tracking over 14 Years

et al. 2015

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f Transposition and homologous recombination of IS6110 appear in Mycobacterium tuberculosis along in vivo sequential infections. These events were checked in different clones of a successful strain, M. tuberculosis Zaragoza, with the focus on a variant in which integration of a copy of IS6110 in the origin of replication (oriC) region occurred. Clonal Mycobacterium tuberculosis variants appear along the sequential infections of hosts involved in the same transmission cluster (1). IS6110 in M. tuberculosis has been one of the most widely used elements in molecular epidemiology and has a transposition rate estimated at ϳ18% over a period of 5 to 6 years (2). The IS6110 element itself modulates expression of neighboring genes and, depending on its location, could confer both transmission ability and virulence (3-5). Microevolution events due to the transposition of IS6110 are usually reflected in variations of restriction fragment length polymorphism (RFLP) patterns (6, 7). Minor variations in IS6110 fingerprints, spoligotypes, or mycobacterial interspersed repetitive-unit (MIRU)-variable-number tandem-repeat (VNTR) loci reveal microevolution in clonal infections (6,8). These changes could have effects on the molecular structure of the mycobacterial genome and the biology of the bacillus (7).Molecular epidemiological studies carried out for more than a decade have provided accuracy in the study of the transmission (9). The usefulness of the approach has been proven, even in countries with low incidences of tuberculosis (10). The M. tuberculosis Zaragoza strain spread in Zaragoza, Spain, and reached 18.7% of all isolates of M. tuberculosis in 2001 to 2004 (11). This strain was classified in principal genetic group 3 and in singlenucleotide polymorphism (SNP) cluster group 6a (12), it demonstrated the rare spoligotype SIT773, and it carried 12 localized copies of IS6110 (13). In addition, in the context of a highthroughput survey of in vivo IS6110 transposition in multiple M. tuberculosis genomes, an additional IS6110 copy was detected in the oriC region in one isolate (14). The purpose of this study was to review the in vivo genomic changes of the M. tuberculosis Zaragoza strain, focusing on this variant.Among the 2,348 isolates collected between 2000 and 2013, 246 were identified as M. tuberculosis Zaragoza by IS6110 RFLP typing (15) and spoligotyping (16) in the context of tuberculosis surveillance in our region. By tracking the strain changes throughout time, we found 7 different variants, i.e., variants 1 to 7 (Fig. 1). An additional copy of IS6110 was detected in six evolved clones, namely, variants 1 to 6. Variant 7 lost one copy in the RFLP pattern and was the only variant that revealed a change in its spoligotyping pattern. Clones 1, 2, 4, 5, 6, and 7 were isolated from only one patient, whereas variant 3 was isolated from 12 patients, as described below.In variant 7, 10 of the 12 IS6110 insertion sites known for M. tuberculosis Zaragoza were confirmed by PCR (13). However, the two nonamplified copies were l...

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confidence: 98%

In Vivo IS 6110 Profile Changes in a Mycobacterium tuberculosis Strain as Determined by Tracking over 14 Years

et al. 2015

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“…Indeed, the presence of independent disruptions of the same gene in different clinical strains, i.e. another example of convergent evolution, might be associated with an evolutionary advantage for the corresponding strains [132]. For example, one hyper-virulent M. bovis strains that caused an outbreak of human TB in Spain showed an IS 6110 insertion upstream of the phoP regulon [98].…”

Section: The Consequences Of Genomic Diversity In Mtbcmentioning

confidence: 99%

Consequences of genomic diversity in Mycobacterium tuberculosis

Coscollá

Gagneux

2014

Seminars in Immunology

389

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The causative agent of human tuberculosis, Mycobacterium tuberculosis complex (MTBC), comprises seven phylogenetically distinct lineages associated with different geographical regions. Here we review the latest findings on the nature and amount of genomic diversity within and between MTBC lineages. We then review recent evidence for the effect of this genomic diversity on mycobacterial phenotypes measured experimentally and in clinical settings. We conclude that overall, the most geographically widespread Lineage 2 (includes Beijing) and Lineage 4 (also known as Euro-American) are more virulent than other lineages that are more geographically restricted. This increased virulence is associated with delayed or reduced pro-inflammatory host immune responses, greater severity of disease, and enhanced transmission. Future work should focus on the interaction between MTBC and human genetic diversity, as well as on the environmental factors that modulate these interactions.

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“…and LAM sub-lineages were assigned to PGG2. The ill-defined T family (PGG3) represents the more modern strains, at least within the dataset used in this study, thus providing data that are an extension to results presented in previous studies (Sreevatsan et al, 1997, Millán-Lou et al, 2013) as they did not describe an association between certain sub-lineages and PGGs. Isolates of PGG3 within this study clustered clonally and made up 42% of the outbreak isolates.…”

Section: 37: Phylogenetic Composition Of Outbreak Isolatessupporting

confidence: 52%

“…The evolution from PGG1 to PGG3 is sequential (Gutierrez et al, 2006), meaning PGG1 isolates represent ancient isolates, PGG2 isolates an intermediate group and PGG3 the most modern group (Sreevatsan et al, 1997., Millán-Lou et al, 2013. In this study, isolates of the Haarlem, X…”

Section: 37: Phylogenetic Composition Of Outbreak Isolatesmentioning

confidence: 76%

Use of Whole Genome Sequencing in Understanding Transmission Dynamics of Tuberculosis

Jones¹

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Mycobacterium tuberculosis is the leading cause of death from an infectious disease worldwide. An understanding of tuberculosis transmission dynamics in outbreak settings is vital for its control. The advent of affordable whole genome sequencing (WGS) has provided scope for superior resolution of tuberculosis outbreaks, compared to previous methods. However, the challenge lies in standardising the vast quantities of resulting data in a structured manner which lends itself to easy comparison of isolates. Gene-by-gene Multi-Locus Sequence Typing (MLST) methods of analysing WGS data, as opposed to Single Nucleotide Polymorphism (SNP) mapping, have shown promise in providing a uniform platform for outbreak resolution. WGS was performed on clinical isolates from three M. tuberculosis outbreaks in South West Wales. Molecular typing by MIRU-VNTR and epidemiological investigation had resulted in conflicting conclusions. Outbreak analysis and phylogenetic typing of all isolates was carried out using the WGS gene-by-gene MLST analysis method of core genome MLST (cgMLST) and traditional WGS SNP mapping. Where DNA quality was unsatisfactory, an ancient DNA library preparation was used successfully. Provean and BEAST software analysis provided physiological

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Global Study of IS 6110 in a Successful Mycobacterium tuberculosis Strain: Clues for Deciphering Its Behavior and for Its Rapid Detection

Cited by 18 publications

References 49 publications

In Vivo IS 6110 Profile Changes in a Mycobacterium tuberculosis Strain as Determined by Tracking over 14 Years

In Vivo IS 6110 Profile Changes in a Mycobacterium tuberculosis Strain as Determined by Tracking over 14 Years

Consequences of genomic diversity in Mycobacterium tuberculosis

Use of Whole Genome Sequencing in Understanding Transmission Dynamics of Tuberculosis

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