IS6110 Copy Number in Multi-Host Mycobacterium bovis Strains Circulating in Bovine Tuberculosis Endemic French Regions

Abstract

IS6110 is an insertion sequence found in the Mycobacterium tuberculosis complex, to which Mycobacterium bovis belongs, which can play a role in genome plasticity and in bacterial evolution. In this study, the abundance and location of IS6110 on M. bovis genomic data of French animal field strains were studied. A first analysis was performed on a panel of 81 strains that reflect the national M. bovis population’s genetic diversity. The results show that more than one-third of them are IS6110 multicopy and that 10% have IS6110 in a high copy number (more than 6 copies). Multicopy strains are those circulating in the regions where prevalence was above the national average. Further study of 93 such strains, with an IS6110 copy number of 10-12, showed stability of IS6110 copy number and genome location over time and between host species. The correlation between M. bovis multicopy strains and high bovine tuberculosis (bTB) prevalence leads us to consider whether their epidemiological success could be partly due to genetic changes originated by IS6110 transposition.

Features of Mycobacterium bovis Complete Genomes Belonging to 5 Different Lineages

“…The phylogenetic distribution of SNPs, shown in Figure 4 , discriminated M. bovis genomes into 10 clusters well resolved by at least 200 SNP. This population structure is congruent with previous studies [ 7 , 53 ]. Indeed, the heatmap clearly highlights lineages based on the absolute SNP distance between strains, which supports a very clear separation between the lineage La1.2 (clusters G+H+I) and lineage La1.8.2 (cluster A+B+C).…”

“…Insertion sequence (IS) analyses showed that all genomes have in the same position one copy of IS 1561 and six copies of IS 1081 , of which one is truncated ( Table 1 ). According to our previous study [ 53 ], the number of IS 6110 is variable depending on the genotype. With 12 copies, Mb1855, which belongs to the Eu3 clonal complex, presents the highest IS 6110 (1355 bp) copy number, which is one of the main reasons for its large genome size.…”

“…Indeed, the 12 copies of IS 6110 in Mb1855 represent an addition of 14,905 bp in comparison to genomes with only one copy of IS 6110 . The complete genomes allowed us to confirm the presence of multiple copies of IS 6110 in certain M. bovis genotypes according to our previous study [ 24 , 53 ]. The transposition of this genetic element can play an important role in bacterial evolution by interrupting or leading to the overexpression of genes [ 53 , 64 , 65 , 66 ].…”

“…The complete genomes allowed us to confirm the presence of multiple copies of IS 6110 in certain M. bovis genotypes according to our previous study [ 24 , 53 ]. The transposition of this genetic element can play an important role in bacterial evolution by interrupting or leading to the overexpression of genes [ 53 , 64 , 65 , 66 ]. Indeed, some genetic changes such as gene deletion or gene pseudogenization that could affect the core genome, can be attributed to IS 6110 .…”

Recent progress in the genotyping of bovine tuberculosis and its rapid diagnosis via nanoparticle-based electrochemical biosensors

“…Another study disclosed M. bovis lineages by applying pangenome analysis, and the results showed 3900 core genes and only 96 accessory genes. 48 Ceres and other scientists have proven that: (1) the accessory genome of M. bovis is noticeably smaller than previously believed, and this nding supports continuing clonal evolution and a closed pangenome with low gene content uctuation throughout outbreaks; (2) several genes have frameshi mutations, including glpK, which has recently been linked to antibiotic tolerance in M. tuberculosis; (3) indels are the primary cause of the minor gene content variation that develops over brief time periods among closely related sequences; (4) multiple genes have potentially reversible homopolymeric tract alterations, indicating that phase variation may be a common method of gene regulation in MTBC. 140…”