Transposition mechanism, molecular characterization and evolution of IS6110, the specific evolutionary marker of Mycobacterium tuberculosis complex

Sarah, Thabet; Souissi, Nada

doi:10.1007/s11033-016-4084-x

Cited by 13 publications

(7 citation statements)

References 78 publications

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“…Differing levels of IS could be related to TB host adaptability [44]. Yet, to date, IS6 110 copy number was not explored in M. bovis although it was considerably less than that in M. tuberculosis , with typically just one insertion noted [45], as also observed in our study. Interestingly, a unique single transposable IS 6110 upstream of the phoPR operon increased its expression, thereby facilitating the dissemination of M. bovis in the human host [46].…”

Section: Discussionsupporting

confidence: 72%

First insights on the genetic diversity of MDR Mycobacterium tuberculosis in Lebanon

et al. 2018

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BackgroundLebanon hosts a heterogeneous population coming from underdeveloped and developing countries, resulting in increasing incidences of tuberculosis over the past years. The genetic heterogeneity and lineages associated with tuberculosis, along with their resistance determinants have not been studied at the genomic level previously in the region.MethodsIsolates were recovered from the American University of Beirut Medical Center (AUBMC). Antimicrobial susceptibility profiles were determined using the MGIT automated system for the first-line drugs at AUBMC, while second-line drug susceptibility was tested at Mayo Clinic Laboratories. Whole Genome Sequencing (WGS) was performed to classify mycobacterial lineages and highlight single nucleotide mutations causing resistance to both 1st line and 2nd line antimicrobials. wgSNP analysis provided insights on the phylogeny of the isolates along with spoligotyping and core genomic SNVs, IS6110 insertion sites, and variable number tandem repeats (VNTR).ResultsThe analyzed isolates carry distinct resistance determinants to isoniazid, rifampicin, ethambutol, quinolones, and streptomycin. The isolates belonged to different lineages including the Euro/American lineage (Lineage 4) (53.8%), M. bovis (15.4%) and Delhi/Central Asia (Lineage 1) (15.4%), Beijing/East Asia (Lineage 2) (7.7%), and East Africa/Indian Ocean lineage (Lineage 3) (7.7%) showing great phylogenetic differences at the genomic level.ConclusionsThe population diversity in Lebanon holds an equally diverse and uncharacterized population of drug resistant mycobacteria. To achieve the WHO “END-TB” milestones of 2025 and 2035, Lebanon must decrease TB incidences by 95% in the next decade. This can only be done through WGS-based patient centered diagnosis with higher throughput and genomic resolution to improve treatment outcomes and to monitor transmission patterns.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3626-3) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 72%

First insights on the genetic diversity of MDR Mycobacterium tuberculosis in Lebanon

et al. 2018

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“…2017). In contrast, the insertion of mycobacterial IS6110 provided a crucial role in elevating the transmission ability and the virulence, which antedated the emergence of the Mycobacterium tuberculosis (Thabet and Souissi 2017). In our study, three genes were disrupted by the insertion of IS Val1 , which might attenuate the virulence of Vp AHPND .…”

Section: Discussionmentioning

confidence: 99%

Coordination of primary metabolism and virulence factors expression mediates the virulence of Vibrio parahaemolyticus towards cultured shrimp ( Penaeus vannamei )

Yang

Zou

et al. 2020

J. Appl. Microbiol.

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Aims Acute hepatopancreatic necrosis disease (AHPND) caused by Vibrio parahaemolyticus has emerged as a severe bacterial disease of cultured shrimp. To identify the key virulence factors, two AHPND‐causing V. parahaemolyticus (VpAHPND) strains (123 and 137) and two non‐VpAHPND strains (HZ56 and ATCC 17082) were selected. Methods and Results Challenge tests showed that the four strains exhibited different virulence towards shrimp with cumulative mortalities at 48 h postinfection (hpi) ranging from 10 to 92%. The expression of pirABVP in strain 123 and 137 was not significantly different. Genomic analysis revealed that the two VpAHPND strains contain a plasmid with the PirABVP toxins (pirABVP) flanked by the insertion sequence (ISVal1) that has been identified in various locations of chromosomes in VpAHPND strains. The two VpAHPND strains possessed almost identical virulence factors, while ISVal1 disrupted three genes related to flagellar motility in strain 137. Phenotype assay showed that strain 123 possessed the highest growth rate and swimming motility, followed by strain 137, suggesting that the disruption of essential genes mediated by ISVal1 significantly affected the virulence level. Transcriptome analysis of two VpAHPND strains (123 and 137) further suggested that virulence genes related to the capsule, flagella and primary metabolism were highly expressed in strain 123. Conclusions Here for the first time, it is demonstrated that the virulence of VpAHPND is not only determined by the expression of pirABVP, but also is mediated by ISVal1 which affects the genes involved in flagellar motility and primary metabolism. Significance and Impact of the Study The genomic and transcriptomic analysis of VpAHPND strains provides valuable information on the virulence factors affecting the pathogenicity of VpAHPND.

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“…In MTC, the CRISPR locus is a likely witness of a previous yet unknown evolutionary history of phage DNA invaders defense, whereas IS6110 is a specific MTC element that belongs to the IS3 family that, through transposition, also plays a permanent role in shaping MTC genomes [56]. The link between the two in evolutionary genomics remains poorly investigated until now.…”

Section: Global Implication Of Crispr Diversity For the Understandingmentioning

confidence: 99%

Unexpected diversity of CRISPR unveils some evolutionary patterns of repeated sequences in Mycobacterium tuberculosis

2020

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Background Diversity of the CRISPR locus of Mycobacterium tuberculosis complex has been studied since 1997 for molecular epidemiology purposes. By targeting solely the 43 spacers present in the two first sequenced genomes (H37Rv and BCG), it gave a biased idea of CRISPR diversity and ignored diversity in the neighbouring cas-genes. Results We set up tailored pipelines to explore the diversity of CRISPR-cas locus in Short Reads. We analyzed data from a representative set of 198 clinical isolates as evidenced by well-characterized SNPs. We found a relatively low diversity in terms of spacers: we recovered only the 68 spacers that had been described in 2000. We found no partial or global inversions in the sequences, letting always the Direct Variant Repeats (DVR) in the same order. In contrast, we found an unexpected diversity in the form of: SNPs in spacers and in Direct Repeats, duplications of various length, and insertions at various locations of the IS6110 insertion sequence, as well as blocks of DVR deletions. The diversity was in part specific to lineages. When reconstructing evolutionary steps of the locus, we found no evidence for SNP reversal. DVR deletions were linked to recombination between IS6110 insertions or between Direct Repeats. Conclusion This work definitively shows that CRISPR locus of M. tuberculosis did not evolve by classical CRISPR adaptation (incorporation of new spacers) since the last most recent common ancestor of virulent lineages. The evolutionary mechanisms that we discovered could be involved in bacterial adaptation but in a way that remains to be identified.

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Transposition mechanism, molecular characterization and evolution of IS6110, the specific evolutionary marker of Mycobacterium tuberculosis complex

Cited by 13 publications

References 78 publications

First insights on the genetic diversity of MDR Mycobacterium tuberculosis in Lebanon

First insights on the genetic diversity of MDR Mycobacterium tuberculosis in Lebanon

Coordination of primary metabolism and virulence factors expression mediates the virulence of Vibrio parahaemolyticus towards cultured shrimp ( Penaeus vannamei )

Unexpected diversity of CRISPR unveils some evolutionary patterns of repeated sequences in Mycobacterium tuberculosis

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