IS6110 in oriC affects the morphology and growth of Mycobacterium tuberculosis and attenuates virulence in mice

Casart, Yveth; Turcios, Lilia; Florez, Ingrid; Jaspe, Rossana C.; Guerrero, Elba; Waard, Jacobus H. de; Aguilar, Diana; Hernández-Pando, Rogelio; Salazar, L

doi:10.1016/j.tube.2008.03.006

Cited by 11 publications

(10 citation statements)

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“…In the non-Beijing strain SUMu003, a copy was observed in a different point other than A1 in the dnaA : dnaN region, indicating that the presence of an IS 6110 in this region is not exclusive to the Beijing family (Figure 2). This result is in agreement with studies which show different locations of IS 6110 in the dnaA : dnaN region in non-Beijing strains [18,19,40]. The amplification of this entire intergenic region is a useful tool to detect Beijing isolates, but another genomic feature of this genotype is also necessary to avoid potential false positive results.…”

Section: Resultssupporting

confidence: 91%

Mapping IS6110 in high-copy number Mycobacterium tuberculosis strains shows specific insertion points in the Beijing genotype

et al. 2013

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BackgroundMycobacterium tuberculosis Beijing strains are characterized by a large number of IS6110 copies, suggesting the potential implication of this element in the virulence and capacity for rapid dissemination characteristic of this family. This work studies the insetion points of IS6110 in high-copy clinical isolates specifically focusing on the Beijing genotype.ResultsIn the present work we mapped the insertion points of IS6110 in all the Beijing strains available in the literature and in the DNA sequence databases. We generated a representative primer collection of the IS6110 locations, which was used to analyse 61 high-copy clinical isolates. A total of 440 points of insertion were identified and analysis of their flanking regions determined the exact location, the direct repeats (DRs), the orientation and the distance to neighboring genes of each copy of IS6110. We identified specific points of insertion in Beijing strains that enabled us to obtain a dendrogram that groups the Beijing genotype.ConclusionsThis work presents a detailed analysis of locations of IS6110 in high-copy clinical isolates, showing points of insertion present with high frequency in the Beijing family and absent in other strains.

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Section: Resultssupporting

confidence: 91%

Mapping IS6110 in high-copy number Mycobacterium tuberculosis strains shows specific insertion points in the Beijing genotype

et al. 2013

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“…Some studies have suggested that the presence of one IS6110 copy in the oriC region increases the duplication time for M. tuberculosis and this effect is independent of the orientation of the insertion element (25). It has also been reported that deletions in the oriC region can abolish the activity at the replication origin and that point mutations in the DnaA boxes severely reduce the activity of oriC.…”

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confidence: 99%

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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“…The presence of the IS in oriC, the region that control the replication of the genome, is expected to have some influence on the synchronization of the bacterial cell division (Casart et al, 2008). This site is currently considered a preferential locus, and multiple transposition events were described in several clinical isolates from patients in Caracas (Venezuela) (Turcios et al, 2009).…”

Section: Is6110 In the Genome Of The Beijing Familymentioning

confidence: 99%

“…This site is currently considered a preferential locus, and multiple transposition events were described in several clinical isolates from patients in Caracas (Venezuela) (Turcios et al, 2009). Both the infection in the animal model as well as the in vitro growth rate were further analyzed for those clinical strains, and compared to strains lacking in IS at the oriC region (Casart et al, 2008). The presence of IS6110 in the origin of replication enlarge the bacilli and causes slow growth rate in vitro; besides the IS apparently causes attenuation in the animal model.…”

Section: Is6110 In the Genome Of The Beijing Familymentioning

confidence: 99%

“…This insertion was identified in many strains including several belonging to the Beijing family (see part 4.1.3). Moreover the IS could be inserted in both directions in this region (Turcios et al, 2009;Casart et al, 2008) having thus putatively a variable influence on the bacterial cell division. Much effort should be used to complete the record of the loci in which IS6110 was inserted.…”

Section: Switching On and Off Genesmentioning

confidence: 99%

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IS6110 the Double-Edged Passenger

Menéndez¹,

Samper²,

Otal³

et al. 2012

Understanding Tuberculosis - Deciphering the Secret Life of the Bacilli

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IS6110 in oriC affects the morphology and growth of Mycobacterium tuberculosis and attenuates virulence in mice

Cited by 11 publications

References 32 publications

Mapping IS6110 in high-copy number Mycobacterium tuberculosis strains shows specific insertion points in the Beijing genotype

Mapping IS6110 in high-copy number Mycobacterium tuberculosis strains shows specific insertion points in the Beijing genotype

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

IS6110 the Double-Edged Passenger

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