Open Access Highly Accessed Research article

Genomic variations associated with attenuation in Mycobacterium avium subsp. paratuberculosis vaccine strains

Tim J Bull1*, Alex Schock2, J Michael Sharp2, Mandisa Greene35, Iain J McKendrick4, Jill Sales4, Richard Linedale1 and Karen Stevenson3

Author affiliations

1 St. George’s University of London Medical School, SW17 0RE, London, UK

2 AHVLA Lasswade, Bush Loan, EH26 0PZ, Penicuik, Midlothian, UK

3 Moredun Research Institute, Bush Loan, EH26 0PZ, Penicuik, Midlothian, UK

4 Biomathematics & Statistics Scotland, James Clerk Maxwell Building, The King’s Buildings, Mayfield Road, EH9 3JZ, Edinburgh, UK

5 Present address: Charter Veterinary Surgeons, 51 Congleton Road, ST8 6EF, Stoke On Trent, UK

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Citation and License

BMC Microbiology 2013, 13:11  doi:10.1186/1471-2180-13-11

Published: 22 January 2013



Mycobacterium avium subspecies paratuberculosis (MAP) whole cell vaccines have been widely used tools in the control of Johne’s disease in animals despite being unable to provide complete protection. Current vaccine strains derive from stocks created many decades ago; however their genotypes, underlying mechanisms and relative degree of their attenuation are largely unknown.


Using mouse virulence studies we confirm that MAP vaccine strains 316 F, II and 2e have diverse but clearly attenuated survival and persistence characteristics compared with wild type strains. Using a pan genomic microarray we characterise the genomic variations in a panel of vaccine strains sourced from stocks spanning over 40 years of maintenance. We describe multiple genomic variations specific for individual vaccine stocks in both deletion (26–32 Kbp) and tandem duplicated (11–40 Kbp) large variable genomic islands and insertion sequence copy numbers. We show individual differences suitable for diagnostic differentiation between vaccine and wild type genotypes and provide evidence for functionality of some of the deleted MAP-specific genes and their possible relation to attenuation.


This study shows how culture environments have influenced MAP genome diversity resulting in large tandem genomic duplications, deletions and transposable element activity. In combination with classical selective systematic subculture this has led to fixation of specific MAP genomic alterations in some vaccine strain lineages which link the resulting attenuated phenotypes with deficiencies in high reactive oxygen species handling.

Mycobacterium avium subspecies paratuberculosis; Vaccine; Comparative genomics; Variable genomic island; Attenuation; Microarray