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Published on: September 27, 2018
Characterisation of IS1311 in Mycobacterium avium subspecies paratuberculosis genomes: Typing, continental
Rachel Mizzi1, Karren M Plain1, Verlaine J Timms2
1School of Veterinary Science, Faculty of Science, The University of Sydney, Sydney, New South Wales, Australia.
Abstract:
Johne's disease (JD), caused by Mycobacterium avium subspecies paratuberculosis (MAP) is a global burden for livestock producers and has an association with Crohn's disease in humans. Within MAP there are two major lineages, S/Type I/TypeIII and C/Type II, that vary in phenotype including culturability, host preference and virulence. These lineages have been identified using the IS1311 element, which contains a conserved, single nucleotide polymorphism. IS1311 and the closely related IS1245 element belong to the IS256 family of insertion sequences, are dispersed throughout M. avium taxa but remain poorly characterised. To investigate the distribution and diversity of IS1311 in MAP, 805 MAP genomes were collated from public databases. IS1245 was absent, while IS1311 sequence, copy number and insertion loci were conserved between MAP S lineages and varied within the MAP C lineage. One locus was specific to the S strains, which contained nine IS1311 copies. In contrast, C strains contained either seven or eight IS1311 loci. Most insertion loci were associated with the boundaries of homologous regions that had undergone genome rearrangement between the MAP lineages, suggesting that this sequence may be a driver of recombination. Phylogenomic geographic clustering of MAP subtypes was demonstrated for the first time, at continental scale, and indicated that there may have been recent MAP transmission between Europe and North America, in contrast to Australia where importation of live ruminants is generally prohibited. This investigation confirmed the utility of IS1311 typing in epidemiological studies and resolved anomalies in past studies. The results shed light on potential mechanisms of niche/host adaptation, virulence of MAP and global transmission dynamics.
Insights
Johne
Area of Science:
- Veterinary Microbiology
- Genomics
- Infectious Diseases
Background:
- Johne's disease (JD), caused by Mycobacterium avium subspecies paratuberculosis (MAP), significantly impacts livestock and is linked to human Crohn's disease.
- MAP exists in two main lineages (S and C) with distinct phenotypes, differentiated by the IS1311 insertion sequence.
- IS1311 and IS1245 elements, part of the IS256 family, are found in M. avium but their role in MAP is not fully understood.
Purpose of the Study:
- To investigate the distribution and genetic diversity of the IS1311 insertion sequence within MAP.
- To analyze the relationship between IS1311 variations, MAP lineages, and potential drivers of genomic rearrangement.
- To explore the phylogenomic and geographic patterns of MAP subtypes and their global transmission dynamics.
Main Methods:
- Collation and analysis of 805 MAP genomes from public databases.
- Comparative genomic analysis focusing on the presence, copy number, and insertion sites of IS1311.
- Phylogenomic analysis to determine geographic clustering and transmission patterns.
Main Results:
- IS1245 was absent in all analyzed MAP genomes; IS1311 was conserved in S lineages but varied in copy number and loci within C lineages.
- MAP S strains exhibited nine IS1311 copies, while C strains had seven or eight, with insertion sites often at homologous region boundaries.
- Demonstrated phylogenomic geographic clustering of MAP subtypes, suggesting recent transmission between Europe and North America.
Conclusions:
- IS1311 typing is a valuable tool for epidemiological studies of MAP, resolving previous inconsistencies.
- IS1311 variations are linked to MAP lineage divergence and may drive genome rearrangements, influencing host adaptation and virulence.
- The study provides insights into the global transmission dynamics of MAP, highlighting potential intercontinental spread.
